Brain tumors pose significant challenges in modern healthcare, with accurate and timely diagnosis crucial for determining appropriate treatment strategies. Artificial intelligence has made significant advancements in recent years. Rule-based expert systems (if-then rule-based systems) have emerged as a promising approach for clinical decision-making in brain tumor diagnosis. In this paper, we present "A CLIPS-Based Expert System for Brain Tumor Diagnosis," which leverages a set of 14 if-then rules to diagnose brain tumors (...) with three possible outcomes: 1) Confirm the diagnosis of a brain tumor, 2) Consider the possibility of a brain tumor that has metastasized, and 3) Consider the possibility of a brain tumor. Our expert system offers a user-friendly interface, enabling users to select symptoms and receive a diagnosis based on the provided information. This paper discusses the expert system's development, implementation, and evaluation, highlighting its potential to facilitate brain tumor diagnosis and decision-making in clinical settings. Additionally, we provide a literature review that contextualizes our expert system within the broader landscape of rule-based expert systems for brain tumor diagnosis, examining their effectiveness, limitations, and challenges. (shrink)

Delicate Tissue Tumors (STT) are a type of sarcoma found in tissues that interface, backing, and encompass body structures. Due to their shallow recurrence in the body and their extraordinary variety, they seem, by all accounts, to be heterogeneous when seen through Magnetic Resonance Imaging (MRI). They are effortlessly mistaken for different infections, for example, fibro adenoma mammae, lymphadenopathy, and struma nodosa, and these indicative blunders have an extensive unfavorable impact on the clinical treatment cycle of patients. Analysts have proposed (...) a few AI models to characterize cancers, however none have sufficiently tended to this misdiagnosis issue. Likewise, comparative investigations that have proposed models for assessment of such cancers generally don't think about the heterogeneity and the size of the information. Thusly, we propose an AI based approach which joins another strategy of pre handling the information for highlights change, resampling methods to dispense with the predisposition and the deviation of precariousness and performing classifier tests in light of the and Deep learning Algorithm as Artificial brain organization. -/- Tumors (STT). (shrink)

Artificial intelligence (AI) is an area of computer science that emphasizes the creation of intelligent machines or software that work and reacts like humans, some of the computer activities with artificial intelligence are designed to include speech, recognition, learning, planning and problem solving. Deep learning is a collection of algorithms used in machine learning, it is part of a broad family of methods used for machine learning that are based on learning representations of data. Deep learning is used as a (...) technique to produce brain tumor detection and classification models using Magnetic Resonance Imaging (MRI) imaging for rapid and easy detection and identification of brain tumor. In this thesis, some ways and mechanisms will be reviewed to use deep learning techniques to produce a model for brain tumor detection. The goal is to find a good and effective way to detect brain tumor based on MRI to help the brain doctor in making decisions easily, accurately and rapidly. A recent report by the World Health Organization in February 2018 showed that the death rate from brain cancer or central nervous system (CNS) is the highest in the Asian continent. It is important to detect cancer early so that many of these lives can be saved. The model has been designed and implemented, including a dataset which consist of 10,000 images for brain tumor detection through the use of Deep learning algorithms based on neural networks. For testing, we have used our model, Inception, VGG16, MobileNet and ResNet models. The f-score accuracy we got for each model was as follows: Our model was 98.28, VGG16 was 99.86%, ResNet50 was 98.14%, MobileNet was 88,98%, and InceptionV3 was 99.88%. (shrink)

The level of accuracy needed to identify the type of tumor using MRI data is necessary to choose the best method for medical care. The K-Nearest Neighbor approach, a fundamental scientific application and image classification technique, can be used to computationally analyze MRI results. The objective of the tumor classification system is to identify the tumor. The only information used to analyze data for this type of system comes from the MRI's axial portion, which are divided into (...) three categories they are: oligodendroglioma, glioblastoma, and astrocyte. Basic image processing techniques, such as image enhancement, image biniarization, morphological image and watershed are used to identify the tumor region. Tumor categorization achieved findings of 89.5 percent, which may provide more precise and in-depth information about tumor identification. (shrink)

In this paper an Artificial Neural Network (ANN) model, for predicting the category of a tumor was developed and tested. Taking patients’ tests, a number of information gained that influence the classification of the tumor. Such information as age, sex, histologic-type, degree-of-diffe, status of bone, bone-marrow, lung, pleura, peritoneum, liver, brain, skin, neck, supraclavicular, axillar, mediastinum, and abdominal. They were used as input variables for the ANN model. A model based on the Multilayer Perceptron Topology was established (...) and trained using data set which its title is “primary tumor” and was obtained from the University Medical Centre, Institute of Oncology, Ljubljana, Yugoslavia Test data evaluation shows that the ANN model is able to correctly predict the tumor category with 76.67 % accuracy. (shrink)

In modern hospitals in developed countries, deaths are determined usually after a prearranged schedule of resuscitative efforts. By default, death is diagnosed and determined after “full code” or after the failure of intensive resuscitation. In end-of-life contexts, however, various degrees of less-than-full resuscitation and sometimes no resuscitation are allowed after the consent and shared decision-making of the patient and/or surrogates. The determination of brain death is a unique exception in these contexts because such an end-of-life care plan is usually (...) not offered until after brain death is declared. This essay analyzes and critiques three arguments for denying the family and/or surrogate a chance to consent to or forego the diagnostic protocol of brain death and choose an alternative end-of-life plan. First, opponents of consent for the determination of brain death argue that presenting it as a selectable end-of-life plan undermines the integrity of death determination. The second argument is that it is inconsistent to allow foregoing the determination of brain death when the determination of circulatory death is non-negotiable. The third argument is that allowing the patient/surrogate to forego the determination of brain death would jeopardize the fair and appropriate utilization of intensive care resources and potentially reduce organ donor pools. After closer conceptual examinations of these three arguments, this essay concludes that these arguments are conceptually and morally problematic. It defends an alternative patient-centered end-of-life care plan based on consent and shared decision-making. (shrink)

Does a diagnosis of brain dysfunction matter for ascriptions of moral responsibility? This chapter argues that, while knowledge of brain pathology can inform judgments of moral responsibility, its evidential value is currently limited for a number of practical and theoretical reasons. These include the problem of establishing causation from correlational data, drawing inferences about individuals from group data, and the reliance of the interpretation of brain findings on well-established psychological findings. Brain disorders sometimes matter for (...) moral responsibility, however, because they change an individual’s moral psychology in a way that is beyond their control. While control over psychological changes is not an excusing factor, brain disorders can mitigate moral responsibility because they confront individuals with new psychological deficits or urges for which their previous moral education and existing external and internal moral resources have not prepared them. (shrink)

The “Human Brain Project” (HBP) is a large-scale European neuroscience and information communication technology (ICT) project that has been a matter of heated controversy since its inception. With its aim to simulate the entire human brain with the help of supercomputing technologies, the HBP plans to fundamentally change neuroscientific research practice, medical diagnosis, and eventually the use of computers itself. Its controversial nature and its potential impacts render the HBP a subject of crucial importance for critical studies (...) of science and society. In this paper, we provide a critical exploratory analysis of the potential mid- to long-term impacts the HBP and its ICT infrastructure could be expected to have, provided its agenda will indeed be implemented and executed to a substantive degree. We analyse how the HBP aspires to change current neuroscientific practice, what impact its novel infrastructures could have on research culture, medical practice and the use of ICT, and how, given a certain degree of successful execution of the project’s aims, potential clinical and methodological applications could even transform society beyond scientific practice. Furthermore, we sketch the possibility that research such as that projected by the HBP may eventually transform our everyday world, even beyond the scope of the HBP’s explicit agenda, and beyond the isolated ‘application’ of some novel technological device. Finally, we point towards trajectories for further philosophical, historical and sociological research on the HBP that our exploratory analysis might help to inspire. Our analysis will yield important insights regardless of the actual success of the HBP. What we drive at, for the most part, is the broader dynamics of scientific and technological development of which the HBP agenda is merely one particularly striking exemplification. (shrink)

In recent years, neuroscience has begun to transform itself into a “big data” enterprise with the importation of computational and statistical techniques from machine learning and informatics. In addition to their translational applications such as brain-computer interfaces and early diagnosis of neuropathology, these tools promise to advance new solutions to longstanding theoretical quandaries. Here I critically assess whether these promises will pay off, focusing on the application of multivariate pattern analysis (MVPA) to the problem of reverse inference. I (...) argue that MVPA does not inherently provide a new answer to classical worries about reverse inference, and that the method faces pervasive interpretive problems of its own. Further, the epistemic setting of MVPA and other decoding methods contributes to a potentially worrisome shift towards prediction and away from explanation in fundamental neuroscience. (shrink)

Objective: Alterations in psychomotor dimension cut across different psychiatric disorders, such as schizophrenia (SCZ) and bipolar disorder (BD). This preliminary study aimed to investigate the organization of intrinsic brain activity in the subcortical-cortical sensorimotor system in SCZ (and BD) as characterized according to psychomotor dimension. -/- Method: In this resting-state functional magnetic resonance imaging (fMRI) study, functional connectivity (FC) between thalamus and sensorimotor network (SMN), along with FC from substantia nigra (SN) and raphe nuclei (RN) to basal ganglia (BG) (...) and thalamic regions, were investigated by using an a-priori-driven and dimensional approach. This was done in two datasets: SCZ patients showing inhibited psychomotricity (n = 18) vs. controls (n = 19); SCZ patients showing excited psychomotricity (n = 20) vs. controls (n = 108). Data from a third dataset of BD in inhibited depressive or manic phases (reflecting inhibited or excited psychomotricity) were used as control. -/- Results: SCZ patients suffering from psychomotor inhibition showed decreased thalamus-SMN FC toward around-zero values paralleled by a concomitant reduction of SN-BG/thalamus FC and RN-BG/thalamus FC (as BD patients in inhibited depression). By contrast, SCZ patients suffering from psychomotor excitation exhibited increased thalamus-SMN FC toward positive values paralleled by a concomitant reduction of RN-BG/thalamus FC (as BD patients in mania). -/- Conclusions: These findings suggest that patients exhibiting low or high levels of psychomotor activity show distinct patterns of thalamus-SMN coupling, which could be traced to specific deficit in SN- or RN-related connectivity. Notably, this was independent from the diagnosis of SCZ or BD, supporting an RDoC-like dimensional approach to psychomotricity. (shrink)

Objective: To evaluate the potential of arterial spin labeling (ASL) as an alternative to FDG-PET in the diagnosis of disorders of consciousness (DOC), we conducted a comparative study of the two modalities. Methods: A total of 36 DOC patients (11 female; mean age = 49.67 ± 14.54 years) and 17 healthy control (HC) participants (9 female; mean age = 31.9 ± 9.6 years) underwent both FDG-PET scans that measure metabolism via glucose uptake and ASL scans that measure cerebral blood (...) flow (CBF). CBF and metabolism in DOC and HC were compared, globally and for seven functional networks. Comparability of the two modalities was estimated using Spearman partial correlation for both global and network levels. Furthermore, a support vector machine (SVM) algorithm was used to train two classifiers to distinguish DOC patients from HC with normalized CBF or metabolism values from the seven networks. Performance of these classifiers was first evaluated through leave-one-subject-out (LOSO) cross-validation within their respective modalities. Subsequently, cross-modal validation was conducted: testing the ASL-trained classifier with PET data (ASL-to-PET validation) and vice versa (PET-to-ASL validation). Performance of each classifier was assessed using receiver operating characteristic (ROC) analysis, with area under the curve (AUC) as the metric. Results: Both modalities showed agreement in decreased CBF and metabolism in DOC patients compared to HC, at both global and network levels. The global brain and most networks showed significant positive partial correlation between CBF and metabolism. SVM classifiers, utilizing activity from seven networks as features, performed well in the both LOSO cross-validation (ASL-trained classifier: accuracy = 83.02%, AUC = 0.95; PET-trained classifier: accuracy = 98.12%, AUC = 0.98) and cross-modal validation (ASL-to-PET validation: accuracy = 84.90%, AUC =0.92; PET-to-ASL validation: accuracy = 73.58%, AUC = 0.93). Conclusion: Our results demonstrate that ASL provides information comparable to FDG-PET for DOC patients; moreover, classifiers trained on ASL data perform comparably well to those trained on FDG-PET data. Therefore, ASL could be a valuable alternative to FDG-PET in the clinical diagnosis of DOC, especially in light of its advantages: ease of acquisition, avoidance of radiation exposure, brevity of scanning time, and lower-cost. (shrink)

Even when brain scans fail to detect a striate lesion, functional evidence for blindsight can be adduced. In the aftermath of an automobile accident, JK became blind. Results of ophthalmic exams indicated that the blindness must be cortical. Nevertheless, multiple MRI scans failed to detect structural damage to the striate cortex. Prior to the accident JK had been an athlete; after the accident he retained some athletic abilities, arousing suspicions that he might be engaged in fraud. His residual athletic (...) abilities—e.g., hitting a handball or baseball, or catching a Frisbee—coupled with his experienced blindness, suggested blindsight. But due to the apparent absence of striate lesions, we designed a series of tasks for temporal and spatial dimensions in an attempt to detect functional evidence of his disability. Indeed, test results revealed compelling neural evidence that comport with his subjective reports. This spatiotemporal task-related method that includes contrasts with healthy controls, and detailed understanding of the patient's conscious experience, can be generalized for clinical, scientific and forensic investigations of blindsight. -/- . (shrink)

In this issue of the Report, James L. Bernat proposes an innovative and sophisticated distinction to justify the introduction of permanent cessation as a valid substitute standard for irreversible cessation in death determination. He differentiates two approaches to conceptualizing and determining death: the biological concept and the prevailing medical practice standard. While irreversibility is required by the biological concept, the weaker criterion of permanence, he claims, has always sufficed in the accepted standard medical practice to declare death. Bernat argues that (...) the medical practice standard may be acceptable on the ground that proving circulatory or brain permanence is sufficient to assure complete accuracy for death diagnosis. -/- The topic requires public deliberation: processes to survey people's opinions and mechanisms to channel their opinions into policy-making. What is at stake is the nature of our society. Do we want an expertocracy, in which an enlightened few design policies for the greater good of the majority and exploit the lack of public knowledge to achieve compliance? (shrink)

This chapter reviews fundamental ethical controversy surrounding the ongoing effort to revise the Uniform Determination of Death Act in the United States. Instead of focusing on the process of the revision itself, the chapter explores the underlying ethical debate over brain death that has been ongoing for many decades and finally culminated in this revision. Three issues are focused: the requirement for consent and personal exemptions before applying brain death for the diagnosis of death; redefining the areas (...) of the brain that have ceased to function in the definition of brain death; and codifying the American Academy of Neurology as the authority to issue the standards of the diagnosis of brain death. The chapter concludes that allowing the personal choice of death determination gives a pragmatic compromise to the disputed definition and practice of diagnosing brain death. So long as all risks and imperfections of the diagnosis are accepted through the consenting process, there is nothing ethically objectionable to continuing the current practice of diagnosing brain death as a successful tool to facilitate heart-beating organ donation without violating the dead-donor rule. By contrast, precluding personal choice and imposing legal restrictions to consent and exemptions would further erode public trust. (shrink)

Infants and children are suffering from a lots of nausea and vomiting problems. Doctors, usually face various difficulties dealing with these problems because of their similarities. In this paper, we present an expert system to help users in getting the correct diagnosis of problems of nausea and vomiting in infants and children (Gastro-esophageal reflux, Gastroenteritis, Systemic Infection, Bowel obstruction, Tumors, A bleeding disease, tonsillitis, and Hepatitis pharynx). Furthermore, this expert system provide information about the disease and how to deal (...) with it. SL5 Object expert system language was used to design and implement this expert system. (shrink)

The Knowledge Based System for Diagnosing Breast Cancer is used to assist medical students to improve their education on diagnosis and counseling the process of analyzing the biopsy image of the microscope, determining the type of tumor and the treatment method for each case and identifying the disease related questions. According to the Ministry of Health in its annual report in Gaza, between 2009 and 2014 there are 7069 cases of breast cancer, and in 2014 there are 1502 (...) cases of breast cancer . We are now in the age of visual information where 65% of the populations are visual learners; the Knowledge Based System is the easiest way to ensure students remember the information in the long term, using visual and textual information. The Knowledge Based System has an easy-to-use interface to help students diagnose the disease and enhance their information about the disease; the system can be used on smart phones. This Knowledge Based System can be divided into three main parts: The first part is specific questions for the patient, to help student to know questions type. The second part is the process of analyzing the biopsy sample image, to see if the biopsy image is intact or infected. The last part is the video shows ways to treat breast cancer in the form of animation. (shrink)

Abstract: The Knowledge-Based System for Diagnosing Breast Cancer aims to support medical students in enhancing their education regarding diagnosis and counseling. The system facilitates the analysis of biopsy images under a microscope, determination of tumor type, selection of appropriate treatment methods, and identification of disease-related questions. According to the Ministry of Health's annual report in Gaza, there were 7,069 cases of breast cancer between 2009 and 2014, with 1,502 cases reported in 2014. In an era dominated by visual (...) information, where 65% of the population are visual learners, the Knowledge-Based System serves as an effective tool to aid long-term information retention by utilizing visual and textual resources. The system features a user-friendly interface, enabling students to diagnose the disease and expand their understanding. Furthermore, it can be accessed via smartphones. The Knowledge-Based System comprises three primary components: Firstly, it provides specific patient-oriented questions to familiarize students with the questioning process. Secondly, it facilitates the analysis of biopsy sample images to determine their integrity and identify potential infections. Lastly, the system incorporates animated videos illustrating various approaches for treating breast cancer. (shrink)

A lipoma is a benign tumor composed of adipose tissue and it is considered as the most common form of soft tissue tumor. Lipomas are soft on palpation, usually movable, and are generally painless. They are widely disseminated benign mesenchymal neoplasms commonly found over the nape of the neck and upper back, shoulders, abdomen, buttocks, and proximal portions of the extremities. Their occurrence in the vulva is said to be so rare that only a few cases have been (...) reported. This case describes a patient; 47 years old who had admitted to our clinic with complaint of vulvar mass localized on labium majus approximately 1 year. Total excision of the mass was made and the pathological examination result was lipoma. Vulvar lipoma occurs in rare and should be kept in mind in the differential diagnosis of the other vulvar masses. (shrink)

The “Expert System for Diagnosing Breast Cancer" is used to assist medical students to improve their education on diagnosis and counseling the process of analyzing the biopsy image of the microscope, determining the type of tumor and the treatment method for each case and identifying the disease related questions. According to the Ministry of Health in its annual report in Gaza, between 2009 and 2014 there are 7069 cases of breast cancer, and in 2014 there are 1502 cases (...) of breast cancer . We are now in the age of visual information where 65% of the populations are visual learners; the expert system is the easiest way to ensure students remember the information in the long term, using visual and textual information. The expert system has an easy-to-use interface to help students diagnose the disease and enhance their information about the disease; the system can be used on smart phones. This expert system can be divided into three main parts: The first part is specific questions for the patient, to help student to know questions type. The second part is the process of analyzing the biopsy sample image, to see if the biopsy image is intact or infected. The last part is the video shows ways to treat breast cancer in the form of animation. (shrink)

Endogenous Cushing syndrome (CS) results from hypercortisolemia caused by excess adrenocorticotropic hormone production in a pituitary adenoma or ectopic tumor, or by an adrenal tumor that directly produces excess cortisol. The diagnosis can usually be ascertained with a reasonable degree of certainty based on clinical and laboratory findings of hypercortisolism. There are patients, however, in whom the production of excess cortisol exhibits a cyclic or intermittent pattern, and, as a result, the clinical symptoms may be quite complex (...) and varied. In these patients the hypothalamic- pituitary-adrenal axis may be normal between cycles, and dexamethasone suppression testing may produce a paradoxical response. In the present article, the authors provide a definition of cyclic Cushing syndrome, review the causes and its potential pathophysiological mechanisms, and discuss the treatment options based on a review of the available literature. (DOI: 10.3171/FOC-07/09/E4). (shrink)

Since the 18th century, one of the key features of diagnosed psychopaths has been “moral colorblindness” or an inability to form moral judgments. However, attempts at experimentally verifying this moral incapacity have been largely unsuccessful. After reviewing the centrality of “moral colorblindness” to the study and diagnosis of psychopathy, I argue that the reason that researchers have been unable to verify that diagnosed psychopaths have an inability to make moral judgments is because their research is premised on the assumption (...) that there is a specific moral faculty of the brain, or specific “moral” emotions, and that this faculty or set of emotions can become “impaired”. I review recent research and argue that we have good reason to think that there is no such distinct capacity for moral judgment, and that, as a result, it is impossible for someone’s “moral judgment faculty” to become selectively disabled. I then discuss the implications of such a position on psychopathy research, the coherence of the disorder, and the moral responsibility of psychopaths. (shrink)

We have begun work on two separate but related ontologies for the study of neurological diseases. The first, the Neurological Disease Ontology (ND), is intended to provide a set of controlled, logically connected classes to describe the range of neurological diseases and their associated signs and symptoms, assessments, diagnoses, and interventions that are encountered in the course of clinical practice. ND is built as an extension of the Ontology for General Medical Sciences — a high-level candidate OBO Foundry ontology that (...) provides a set of general classes that can be used to describe general aspects of medical science. ND is being built with classes utilizing both textual and axiomatized definitions that describe and formalize the relations between instances of other classes within the ontology itself as well as to external ontologies such as the Gene Ontology, Cell Ontology, Protein Ontology, and Chemical Entities of Biological Interest. In addition, references to similar or associated terms in external ontologies, vocabularies and terminologies are included when possible. Initial work on ND is focused on the areas of Alzheimer’s and other diseases associated with dementia, multiple sclerosis, and stroke and cerebrovascular disease. Extensions to additional groups of neurological diseases are planned. The second ontology, the Neuro-Psychological Testing Ontology (NPT), is intended to provide a set of classes for the annotation of neuropsychological testing data. The intention of this ontology is to allow for the integration of results from a variety of neuropsychological tests that assay similar measures of cognitive functioning. Neuro-psychological testing is an important component in developing the clinical picture used in the diagnosis of patients with a range of neurological diseases, such as Alzheimer’s disease and multiple sclerosis, and following stroke or traumatic brain injury. NPT is being developed as an extension to the Ontology for Biomedical Investigations. (shrink)

Parkinson’s disease is a common movement disorder associated primarily with oxidative stress-mediated degeneration of dopaminergic neurons. Earlier studies showed that Sorghum bicolor-based supplement (SbS) exhibited antioxidant and neuroprotective activities and might likely rescue the death of dopaminergic neurons in Parkinson’s disease. This study examined the effect of SbS on rotenone-induced Parkinsonian-like motor deficits in rats and the involvement of oxidative stress and pro-inflammatory cytokines. Rats were divided into six groups and treated orally with sunflower oil (vehicle-control), rotenone (2.5 mg/kg) alone (...) or in combination with each dose of SbS (50, 100, and 200 mg/kg) and levodopa-carbidopa (10 mg/kg) on an alternate day for 28 days. The changes in motor functions were evaluated on day 28 and the brain concentrations of oxidative stress biomarkers and pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) were determined. Rotenone caused motor deficits by impaired locomotor activity in the open field test and induced catalepsy in the bar test, which were attenuated by SbS. Rats pretreated with SbS had reduced brain levels of malondialdehyde, nitrite, and pro-inflammatory cytokines compared to rotenone controls. SbS mitigated rotenone-induced depletion of reduced glutathione and antioxidant enzymes in the rat brain. The results suggest that SbS ameliorated rotenone-induced Parkinsonian-like motor dysfunctions by reducing neuronal oxidative stress and pro-inflammatory cytokines in rats. (shrink)

If each of the subtypes of autism is defined simply as constituted by a set of symptoms, then the criteria for its observation are straightforward, although, of course, some of those symptoms themselves might be hard to observe definitively. Compare with telling whether or not someone is bleeding: while it might be hard to tell if someone is bleeding internally, we know what it takes to find out, and when we have the right access and instruments we can settle the (...) issue. But matters are not so simple for the autism subtypes. For one thing, how do we settle which symptoms to group together under one heading? One key difference between “autism disorder” and “Asperger’s disorder” is that the former exhibit language delays (sometimes extreme), whereas the latter do not. But is that a sign of genuinely distinct conditions or is that an artifact of the distinct groups of subjects that Leo Kanner and Hans Asperger worked with? And in general, although there are certainly types of behavior that are taken to be indicative of autism, none by itself is taken by diagnosticians to be either necessary or sufficient for a definitive diagnosis for any of the autism subtypes. What is the diagnostician to do? This is not merely an academic issue, as many parents can attest. Are we in a situation, then, that each practitioner has his or her own “pet” signs that are the “real keys” to the diagnosis? That would suggest that the term “autistic” might meet the fate of the outdated term “neurotic,” which turned out to be a pseudo-scientific term for an inexact clumping together of unrelated phenomena. The assumption amongst specialists seems to be that we will reach the point with "autism" that we have with "water": there will be a root essence to autism whose presence or absence settles a diagnosis. If that is to be the case, however, we have to settle the level of application of the concept. Does the term apply to people who exhibit particular behaviors? Or is it possible to exhibit “autistic” behaviors without actually being autistic, because autism is instead a particular feature of the mind (as, for example, in Baron-Cohen’s “impaired theory of mind module” theory, discussed below) which usually but not necessarily has behavioral effects? Or is autism located instead in the brain, perhaps in damage to key areas, which in turn would typically have an effect on modules of the mind? Or perhaps autism is located in genetics or biology, so that some people with damage to the brain caused by accidents so that they exhibit autistic symptoms would not actually be autistic. Conversely, supposing one had an “autistic brain” but showed none of (or not a sufficient number of) the symptoms, would one not be autistic? The assumption is that the genotypes and phenotypes will line up neatly, but if they do not, what happens to the concept “autistic?” (There is an analogy in the philosophy of sex and gender: androgen insensitive individuals tend to self-identify as female and have outward female traits, but have XY chromosomes—should we go with chromosomes or self-identity in assigning sex category?) Finally, the implications for these complications for diagnosis and categorization, with the attendant social and medical implications is discussed. The typical assumption of the medical profession is that autism cannot be “cured.” That assumes that autism is not simply the symptoms. However, at the same time, the tests used to diagnose ASDs work simply from the symptoms (for example, Baron-Cohen’s Sally/Anne test, which ASD children of a certain age almost all fail, but which practically no ASD adult fails). This implies an inherent confusion over the status of the concept. I conclude that attempts to make sense of some true or accurate summary of what it is to be autistic (such as one would find in the DSM) are almost certainly misguided and will vanish into history along with “neurotic.” But as with racial terms, which are similarly shifting and perverse, the term has already passed into the public sphere and will have a lasting and dangerous influence beyond its short scientific shelf-life. (shrink)

DIFERENCIAÇÃO SEXUAL -/- Emanuel Isaque Cordeiro da Silva Instituto Agronômico de Pernambuco Embrapa Semiárido -/- • _____OBJETIVO -/- Os estudantes de Veterinária e de Zootecnia estão ligados à disciplina Reprodução Animal, um pelos mecanismos fisiológicos para evitar e tratar as possíveis patologias do trato reprodutivo dos animais domésticos, e outro para o entendimento dos processos fisiológicos visando o manejo reprodutivo e a procriação para a formação de um plantel geneticamente melhorado. Sendo assim, a finalidade do presente trabalho é apresentar os (...) mecanismos que regulam as diferenças sobre o desenvolvimento embrionário relativos à diferenciação e determinação sexual de machos e fêmeas, que também incluem o desenvolvimento dos órgãos envolvidos na reprodução e a origem das diferenças entre ambos os sexos. -/- •____INTRODUÇÃO -/- Os organismos que se reproduzem sexualmente são descendentes de organismos ao qual não existia a diferenciação sexual. Em algum momento da evolução surgiu a reprodução sexual como um mecanismo para incrementar a diversidade genética e facilitar a troca de informações genéticas mediante o material genético da fêmea com o do macho. Devido sua origem comum, na maioria das espécies, tanto os machos como as fêmeas possuem todos os genes necessários para desenvolverem-se em qualquer dos sexos. O que efetivamente faz diferença entre os sexos é a forma e a ordem ao qual se expressam os genes durante o processo de desenvolvimento. A diferenciação sexual é regulada principalmente por mecanismos epigenéticos, mais do que as diferenças genéticas de grande magnitude entre os sexos. Todo o controle epigenético de qualquer processo de desenvolvimento depende basicamente de uma série de expressões gênicas, através da qual a expressão de certa combinação de genes resulta na presença de determinadas proteínas, conhecidas como os fatores de transcrição, que induzem ou reprimem a expressão de outro(os) gene(es), a partir dos quais se produzem novas proteínas, que em certos casos também atuam como fatores de transcrição para outros genes, e assim sucessivamente. Logo, a expressão ou falta de expressão de um gene ao início da série pode resultar em um ladrão totalmente diferente da expressão de outros genes subsequentes, o que pode ocasionar profundas mudanças no processo de desenvolvimento e até a mutações indesejáveis. O padrão predeterminado de expressões gênica relativo a diferenciação sexual na maioria das espécies tanto domésticas quanto selvagens, leva ao desenvolvimento de um dos sexos (o padrão predeterminado dos mamíferos é o sexo feminino). Em consequência, a diferenciação faz com que um indivíduo do sexo oposto exija a expressão de um gene de determinação sexual que desvie a subsequente série de expressões gênica em direção ao dito sexo. Nos mamíferos, a expressão do gene SRY, localizado no cromossomo Y (e portanto ausente nas fêmeas), redige o padrão de diferenciação sexual de sua via pré-estabelecida feminina em direção ao padrão masculino. A existência de uma única diferença genética (presença do gene SRY nos machos e ausentes nas fêmeas), vai se amplificando e termina resultando no desenvolvimento de indivíduos diferentes entre si. Esse é um mecanismo de diferenciação sexual cromossômica. O primeiro passo de uma série de diferenciação sexual, em sentido estrito, não depende nem requer necessariamente a presença de um gene diferente em algum dos sexos. O gene “disparador” da diferenciação sexual pode estar presente em todos os embriões, porém pode expressar-se somente em algum deles, devido a fatores ambientais que formam parte da sua regulação epigenética, isto é, uma determinação sexual ambiental. Em algumas espécies de tartarugas ou de lagartos a expressão ou falta de expressão do gene “disparador”, por exemplo, depende da temperatura existente durante a incubação dos ovos, pelo qual alguns embriões desenvolvem-se como machos e outros como fêmeas, apesar de não existir diferença genética entre eles, simplesmente como consequência da temperatura: a determinação sexual depende da temperatura a que cada um deles foi submetido durante a incubação. Em certas espécies as temperaturas mais elevadas facilitam o desenvolvimento de fêmeas e outras de machos, enquanto que em outras espécies as temperaturas amenas (intermediárias) resultam em machos, e as inferiores como as superiores induzem o desenvolvimento de fêmeas. A existência dessa diversidade indica que a temperatura por si mesma não é a que induz ou a que provoca o desenvolvimento do macho e da fêmea, senão a que atua somente como um regulador inicial da diferenciação sexual. Em outras espécies o fator ambiental que regula a determinação sexual pode ser distinto. A densidade populacional, por exemplo, pode atuar como um regulador. Podemos concluir que a determinação sexual dependente da temperatura ou de outros fatores ambientais estabelece-se antes da determinação sexual cromossômica, a qual evoluiu depois como um método que oferece maior certeza e resultado, já que a proporção de machos e fêmeas não é afetada por mudanças ambientais ou de hábitat. -/- •___FORMAÇÃO INICIAL DA GÔNADA -/- Basicamente em todos os embriões, inicialmente se formam as chamadas gônadas indiferenciadas (com o potencial de desenvolver-se em ovários ou testículos) a partir da invasão das cristas genitais pelas células germinais primordiais, que migram desde seu local de origem no epiblasto, perto do lugar onde o saco vitelino se une com o intestino primitivo e que chegam até às cristas genitais que são engrossamentos de tecido situados na região mesonéfrica do embrião. A migração das células germinais primordiais ocorre muito cedo sobre o processo de desenvolvimento do embrião (dia 26 nos bovinos). Ao chegas as cristas genitais, as células germinativas proliferam-se e se organizam com as células somáticas já existentes nas cristas para ir formando a gônada (figura 1). Para regular essa remodelação e conformação adequada da gônada vários genes se expressam, como o OCT-4 (que aparentemente mantém a totipotencialidade da gônada), assim como o SF-1 (Fator esteroidogênico 1) e o WT-1 (gene associado ao tumor de Wilms). Esses dois últimos genes estimulam a proliferação celular e estabelecimento dos cordões sexuais. Nessa etapa inicial do desenvolvimento todos esses genes se expressam sem distinção de sexo, pelo que a gônada em formação mantém a capacidade de se diferenciar em testículo ou em ovário. -/- Figura 1: migração das células germinais primordiais em direção a crista gonodal. Diferenciação das gônadas femininas e masculinas. Fonte: ZARCO, 2018. -/- •___SEXO CROMOSSÔMICO -/- Têm-se observado que nos mamíferos a determinação sexual depende diretamente dos cromossomos. As fêmeas possuem dois cromossomos sexuais X (um contribuído do óvulo e o outro por um espermatozoide “X”). Os machos, por sua vez, possuem um cromossomo sexual X(proveniente do óvulo) e um cromossomo sexual Y, que provém de um espermatozoide “Y” (figura 2). A metade dos espermatozoides produzidos por um macho são X e a metade Y, isso porque durante a espermatogênese a divisão meiótica provoca que a partir de cada espermatócito primário, célula diploide que por pertencer a um indivíduo macho tem um cromossomo X e um Y, se originem das espermátides haploides a cada um das que eles tocam cromossomos X, e outras espermátides haploides as que eles tocam os cromossomos Y. Dessa forma, de acordo com o tipo do espermatozoide que fertilize o ovócito, se originará um indivíduo com cariótipo feminino “XX” ou um cariótipo masculino “XY” (figura 2). Esse processo é conhecido como sexo cromossômico, ao qual se determina o momento da fertilização. Figura 2: nos mamíferos todos os óvulos produzidos pelas fêmeas possuem um cromossomo sexual X. A metade dos espermatozoides produzidos pelos machos possuem um cromossomo X e a outra metade possui um cromossomo Y. Dependendo do cromossomo presente no espermatozoide que fertilize o óvulo pode-se gerar um indivíduo XX (fêmea) ou um XY (macho). Fonte: ZARCO, 2018. -/- O cromossomo “Y” é uma “invenção” relativamente recente na história da evolução das espécies e do estudo da genética. Surgiu a partir de uma mutação de um cromossomo “X”, que resultou na perda de um de seus braços, que é por onde se originou a morfologia do cromossomo Y. A maioria dos genes presentes no cromossomo Y também existem no cromossomo X; assim mesmo somente alguns genes do cromossomo Y foram evoluídos até ser diferentes dos genes do cromossomo X. Embora os machos possuam um cromossomo que não está presente nas fêmeas, esse mesmo cromossomo não aporta toda a informação genética original. Todos os genes existentes nas fêmeas estão também presentes nos dos machos, já que eles também possuem um cromossomo X. Uma particularidade do cromossomo Y, ao existir somente uma cópia nos machos, é que ele sofre um entrecruzamento com um cromossomo análogo durante o processo de meiose, pelo que o cromossomo Y de um macho é idêntico ao de seu progenitor e ao de seus descendentes, exceto no caso em que ocorra uma mutação espontânea. Em contraste, os cromossomos X das fêmeas (um proveniente do pai e outro da mãe) se entrecruzam durante a meiose, por onde cada óvulo produzido pela fêmea terá uma combinação de alelos distinta em seu cromossomo X. Ao estudar as diferenças presentes na sequência de DNA do cromossomo Y, é possível identificar a distância filogenética entre os indivíduos (quanto mais diferenças existirem entre os cromossomos significa que seu ancestral comum está mais longe). Algo análogo ocorre com o DNA das mitocôndrias, que sempre são aportados pela mãe e nunca sofrem recombinação genética. Gene SRY -/- Um dos poucos genes do cromossomo Y que não possuem correspondência com o cromossomo X é o gene SRY (Sex-determining Region of the Y chromossome – região do cromossomo Y determinante do sexo). Esse gene se expressa somente na gônada em formação nos embriões machos, em particular em células precursoras das células de Sertoli; ele codifica uma proteína da família SOX (SRY-like Box) que é uma família formada por proteínas que possuem um domínio de união ao DNA e que atuam como fatores de transcrição. Ao produzir-se a proteína SRY nas células precursoras das células de Sertoli estimula-se a expressão (transcrição) de outro gene análogo, denominado SOX-9 que, por sua vez, atua como um fator de transcrição que ativa a expressão de outros genes, como o FGF-9 (Fibroblast Growth Factor-9), ou seja ele é o estimulante de ativação dos demais. Os produtos dos genes SOX-9 e FGF-9 iniciam uma cascata de expressões que provocam a diferenciação das células de suporte da gônada indiferenciada (crista genital) em células de Sertoli. Em seguida, essas células dirigem a diferenciação das células intersticiais da crista genital em células de Leydig, o que finalmente resulta na formação de um testículo. Outro dos efeitos da proteína codificada por SOX-9 é um estímulo maior da expressão de seu próprio gene, pelo qual é produzido um ciclo de retroalimentação positiva que favorece a continuidade do processo de formação testicular. Como nos embriões da fêmea não existe o gene SRY, a gônada indiferenciada não é estimulada para expressar os genes SOX-9 nem o FGF-9 nas células de suporte (que nesse caso serão precursoras de células da granulosa). A gônada, em mudança, expressa em forma constitutiva, isto é, sem a necessidade de estimulação, outra cascata de genes que incluem o WNT4 (Wingless-integration Factor 4) e o RAPO1 (Respondina-1), que por sua vez iniciam uma cascata de expressão gênica, a qual provoca a diferenciação das células somáticas da gônada indiferenciada para formação das células da granulosa e células da teca, esse feito conduz, por sua vez, a formação de um ovário. No embrião macho a proteína SOX-9 inibe a expressão dos genes WNT4 e RSPO-1, pelo que a presença do gene SRY, e portanto de SOX-9, inibem a formação de um ovário ao mesmo tempo que estimulam a formação do testículo (figura 3). Em suma, se o embrião possui genótipo XY (um embrião macho), o gene SRY começa a expressar-se sobre as células precursoras da gônada imediatamente depois da formação da mesma, quando os cordões sexuais primários estão se desenvolvendo na medula. A expressão do gene, assim como a presença subsequente das proteínas SOX-9 e FGF-9 estimula a distinção das células de Sertoli e que se organizem os tubos seminíferos a partir dos cordões sexuais primários. Em contrapartida, em um embrião com genótipo XX (fêmea) não existe o gene SRY, pelo qual é impossível que se elevem os níveis das proteínas SOX-9 e FGF-9 e as células precursoras não se diferenciam em células de Sertoli, e portanto os cordões sexuais primários sofrem regressão. Depois de alguns dias, começam a organizar-se os cordões sexuais secundários e as células precursoras iniciam a expressão do gene WNT4, o que leva as mesmas a diferenciar-se em células da granulosa, que serão a base para a conformação dos folículos ovarianos. Se em um embrião XY, macho, a expressão do gene SRY demora, é formada um ovo-testículo devido a que algumas das células somáticas das cristas gonodais começam a expressar o gene WNT4, e a diferenciar-se em células da granulosa, enquanto que em outras a proteína SRY chega a tempo para dirigir a diferenciação para formação das células de Sertoli. No ovário em formação é expressado um gene denominado DAX-1 (Dosage-sensitive Sex Reversal). Esse gene, localizado no cromossomo X, codifica uma proteína que é um membro da família dos receptores nucleares ao que lhe falta o domínio de união ao DNA, pelo que parece atuar no bloqueio de diversos fatores de transcrição, entre os que se encontra o SRY. Como a proteína DAX-1 impede a ação da proteína SRY, um excesso de expressão do gene DAX-1 pode provocar a feminilização gonodal de indivíduos XY, macho, embora tenham SRY. Em condições normais, a expressão adequada do gene DAX-1 não é capaz de evitar a masculinização gonodal de embriões com o gene SRY, daqui o nome de reversão sexual dependente da dose. Figura 3: série de expressão gênica para a determinação gonodal. SRY (Região do cromossomo Y determinante do sexo), SOX-9 (SRY-like Box-9), FGF-9 (Fator de crescimento de fibroblastos-9), WNT4 (Wingless-integration Factor-4), RSPO-1 (Respondina-1). Uma vez que o SRY induz a expressão de SOX-9 na gônada masculina, inicia-se um processo de feedback positivo mediante o qual os níveis de expressão de SOX-9 e FGF-9 vão aumentando, ao mesmo tempo que inibem a expressão de WNT-4 e RSPO-1. Na gônada feminina não se expressam SRY, SOX-9 e nem FGF-9, o que permite que se expressem os genes WNT-4 e RSPO-1, que iniciam uma cascata de sinalização que dirige a formação de um ovário. Fonte: ZARCO, 2018. -/- • ___DIFERENCIAÇÃO SEXUAL DOS GENITAIS -/- Uma vez que se formam os testículos, todo o desenvolvimento subsequente dos órgãos e as características “masculinas” em lugar das femininas é em consequência dos hormônios produzidos pelos testículos em formação, incluindo os andrógenos e o hormônio inibidor dos ductos de Müller. Mediante a ausência de testículos todo o desenvolvimento dos órgãos genitais internos e externos segue um padrão feminino, sem levar em conta se estão presentes os ovários; o que significa a ausência de hormônios gonodais determina que o embrião se desenvolva como fêmea, uma vez que não requerem hormônios ovarianos para desencadear o padrão feminino. Por sua vez, as gônadas masculinas (os testículos), produzem substâncias que desviam o desenvolvimento em direção ao padrão masculino. Sob etapas relativamente rápidas da diferenciação todos os embriões possuem dois pares de dutos sexuais, os dutos de Wolff ou mesonéfricos e os dutos de Müller ou paramesonéfricos (figura 4). A testosterona secretada pelos testículos do feto macho em desenvolvimento atua sobre os dutos de Wolff, o que induz a formação posterior dos dutos deferentes, do epidídimo e das glândulas seminais (figura 4). Figura 4: formação dos órgãos genitais internos a partir dos dutos de Wolff no macho e dos dutos de Müller na fêmea. Fonte: ZARCO, 2018. -/- Os testículos produzem ao mesmo tempo, uma glicoproteína chamada Hormônio Inibidor dos Dutos de Müller (Müllerian Inhibiting Hormone, MIH, também chamado de Anti-Müllerian Hormone, AMH); como o seu nome indica, inibe o desenvolvimento dos dutos de Müller ou paramesonéfricos, provocando sua regressão, que impede a formação dos órgãos genitais característicos da fêmea como os ovidutos, o útero, a cérvix e a porção cranial da vagina (figura 4). O MIH é uma glicoproteína da família dos fatores de crescimento transformativo β (TGFβ). O gene MIH possui locais de união para os produtos dos genes SOX-9 e SF-1, pelo que a presença simultânea de ambos fatores de transcrição é necessária para a secreção do MIH e leva a cabo sua função de iniciação dos dutos de Müller sobre o embrião macho (vale lembrar que nessa etapa tanto a gônada de embriões machos como de embriões fêmeas expressam o gene SF-1, mas somente o macho expressa o SOX-9, para que unicamente esse último produza MIH). O certo é que na gônada do embrião fêmea não se produzem quantidades importantes da proteína SOX-9, além de que se produz a proteína DAX-1, mesma que antagoniza tanto a SOX-9 como a SF-1, todo o qual impede a produção de MIH e resulta no desenvolvimento dos dutos de Müller até a formação dos ovidutos, útero, cérvix e a porção cranial da vagina (figura 4). Assim, na fêmea, ao não haver testículos não circulam concentrações elevadas de andrógenos, o que impedirá o desenvolvimento dos dutos de Wolff, enquanto que os dutos de Müller se desenvolvem já que não haverá a presença do MIH para impedi-lo. O desenvolvimento dos genitais internos e externos femininos não requerem a presença de nenhum hormônio ovariano o que levará a cabo de maneira predeterminada (ou pré-estabelecida) na ausência de testículos. Outra estrutura interna que também se desenvolve de forma distinta nos machos e nas fêmeas é o seio urogenital, que no embrião macho é estimulado pela testosterona para formação da próstata, das glândulas bulbouretrais e da uretra peniana, enquanto que na fêmea forma a porção caudal da vagina. A respeito dos órgãos genitais externos (figura 5), nos embriões de ambos os sexos existem estruturas precursoras chamadas de tubérculo genital e pregas vestibulares. Na fêmea o tubérculo genital da origem ao clitóris e as pregas vestibulares dão origem aos lábios vulvares sem a necessidade da atuação de hormônios ovarianos, já que o padrão “por via pré-estabelecida” é feminino. Em contrapartida, no macho, tanto o tubérculo genital quanto as pregas vestibulares respondem ao hormônio 5α-dehidro-testosterona (DHT), ao qual se formam as células da pele da zona genital a partir da testosterona que é secretada pelos testículos. Para isso existem nas células a enzima 5α-reductasa, que transforma a testosterona em DHT. Uma vez formada, a DHT atua sobre as pregas vestibulares do embrião macho para que se fusionem e formem o escroto (em lugar dos lábios vulvares), e sobre o tubérculo genital para formar o pênis (em lugar do clitóris). Figura 5: estruturas que se desenvolvem nos embriões de cada sexo a partir do seio urogenital, o tubérculo genital e as pregas vestibulares. A cor do né de cada estrutura final corresponde com a cor do nome da estrutura a partir da qual se originou. Fonte: ZARCO, 2018. -/- • ___DIFERENCIAÇÃO SEXUAL DO SISTEMA NERVOSO -/- Existem inúmeras diferenças funcionais entre o sistema nervoso da fêmeas e o do machos, em humanos podem incluir diferenças tão complexas como a maior capacidade de verbal da mulher ou a maior capacidade de orientação espacial do homem. Nessa parte será abordada aquelas diferenças que influenciam diretamente sobre a função reprodutiva, como as diferenças na regulação da secreção de gonadotropinas ou as diferenças na capacidade de comportamento sexual masculino ou feminino. É necessário lembrar que, apesar de que essas diferenças se originem durante um período crítico da vida fetal ou neonatal (dependendo da espécie), geralmente se fazem presentes até que o animal chegue a vida adulta e demonstre obter ou não a capacidade para se comportar como macho ou como fêmea uma vez que é exposto aos hormônios sexuais que são secretada depois da puberdade. Igualmente aos processos acima citados, podemos afirmar que nos mamíferos o padrão pré-estabelecido de comportamento sexual e de secreção de gonadotropinas é o feminino. Se durante os primeiros dias de vida neonatal uma rata fêmea não é exposta a nenhum hormônio gonodal, ao chegar a vida adulta ela terá a capacidade de se comportar como fêmea na presença de estrógenos, assim como de secretar um pico pré-ovulatório de GnRH/LH em resposta aos mesmos (figura 6). Essa rata, portanto, não poderá se comportar como macho embora que em sua vida adulta seja exposta a testosterona. O sistema nervoso do rato macho recém-nascido que é exposto aos andrógenos produzidos pelos testículos, em detrimento, faz com que adquiram o potencial para se comportar como machos em sua vida adulta e que perdem o potencial para ter conduta de fêmeas na presença e/ou administração de estrógenos (processo conhecido como desfeminização do SNC). Se por meios de experimentos injetamos testosterona em uma rata fêmea recém-nascida, essa rata não poderá se comportar como fêmea em sua vida adulta, e passará a se comportar como macho. A castração neonatal de um rato (visando evitar a exposição de seu SNC a andrógenos testiculares), assim mesmo, resultará em sua vida adulta um padrão feminino (SNC feminizado e não masculinizado). O hipotálamo das ratas adultas possui uma área em que o número, características e densidade dos corpos neurais difere em machos e fêmeas, essa área é denominada como “núcleo sexualmente dimórfico do hipotálamo”, e tem demonstrado que quando as ratas são tratadas com testosterona na vida neonatal, a morfologia de seu núcleo sexualmente dimórfico será masculinizado em sua vida adulta, enquanto que a castração neonatal de ratos resulta em um núcleo sexualmente dimórfico feminizado em sua vida adulta. Isso significa que a exposição ou não a testosterona na vida neonatal é o que determina que tipo de núcleo sexualmente dimórfico se desenvolverá, o que por sua vez está relacionado com o tipo de conduta que o animal poderá expressar em sua vida adulta. Não deixa de ser um paradoxo que ao injetar uma dose elevada de estrógenos nos primeiros dias de vida de uma rata, os núcleos sexualmente dimórficos da mesma se desenvolverão como macho e em sua vida adulta seu potencial de conduta estará masculinizado e desfeminizado. O hormônio “feminino” conhecido como estradiol, masculiniza o hipotálamo e a conduta do animal. Logo, se a rata neonatal for exposta a injeção de andrógeno não-aromatizado (que não pode ser transformado em estrógenos pelas células) ela não se masculiniza. A masculinização e desfeminização dos ratos ou das ratas tratados com testosterona, na realidade, não são provocados pela própria testosterona, senão pelos estrógenos que se formam dentro dos neurônios quando absorvem a testosterona do sangue e a aromatizam para transformá-la em estrógenos (figura 6). Figura 6: desfeminização e masculinização do sistema nervoso central por meio da testosterona, que quando não absorvida pela α-fetoproteína pode entrar nos neurônios, onde se aromatizam para serem transformados em estrógenos, hormônio que é responsável pela desfeminização. Fonte: ZARCO, 2018. Por que as ratas, que possuem ovários funcionalmente produtores de estrógenos, não se masculinizam? A resposta está em uma proteína denominada α-fetoproteína que circula em altas concentrações nos fetos e nos recém-nascidos. Essa proteína possui a capacidade de unir-se aos estrógenos, ao qual impede seu entrada nas células. Os ratos, em desenvolvimento, produzem testosterona, no entanto não possui afinidade pela α-fetoproteína, o que permite com que ela circule livremente. Ao chegar ao SNC, a testosterona (que não foi absorvida) pode entrar nos neurônios e dentro deles se aromatizam e transformam-se em estrógenos, que finalmente masculinizam o SNC. A diferenciação sexual do hipotálamo depende, em síntese, da presença ou ausência dos testículos, o que permite que se produza ou não o hormônio testosterona que pode não ser absorvida por parte da α-fetoproteína, transformar-se em estrógenos e masculinizar o SNC. -/- •___CONCLUSÃO -/- Nos mamíferos todo o processo que se requerem para o desenvolvimento de um macho depende da existência de somente um gene do cromossomo Y, o gene SRY; a ausência desse gene resulta no desenvolvimento de uma fêmea. A presença ou ausência do gene SRY determina, então, a cadeia de eventos morfogênicos que ocorrerá em sua expressão ou não, para desenvolver todos os órgãos e características de um macho ou de uma fêmea. Por essa razão, os indivíduos com uma monossomia XOA (síndrome de Turner) são fêmeas (por não possuir o cromossomo Y nem o gene SRY), enquanto que os indivíduos triploides XXY (síndrome de Kleinefelter) são machos embora possuam dois cromossomos X. Em algumas espécies, no entanto, têm-se identificado machos que são cromossomicamente XX; nesses casos é determinado invariavelmente que por ser um erro durante a meiose a região do cromossomo Y em que reside o gene SRY tem sido transloucada ao cromossomo X. Da mesma forma, em alguns casos tem sido encontrado fêmeas com cariótipo XY; que nelas se identifica uma mutação inabilitante do gene SRY. Isso demonstra experimentalmente que por meio da engenharia genética é possível produzir machos com cariótipo XY mas com o gene SRY eliminado (knockout). Como é de se esperar, esses machos desenvolvem ovários e todos seus órgãos genitais, tanto internos quanto externos, e se desenvolvem como fêmeas. Os machos cromossomicamente XX transgênicos aos que se insertam uma cópia do gene SRY, desenvolvem testículos e um fenótipo masculino, embora sejam estéreis por causa da ausência de alguns genes do cromossomo Y que são necessários para a realização de uma espermatogênese normal. As falhas nos mecanismos de diferenciação sexual podem, diretamente, ocasionar anormalidades como as observadas nas bezerras Freemartin, que são bezerras originadas de uma gestação gemelar em que seu gêmeo era macho. O que sucede é que na espécie bovina, quando há uma gestação gemelar, é produzido um certo grau de anastomose entre as placentas dos fetos, o que permite a troca de sangue e de células entre ambos. Os produtos recebem, então, algumas células de seu gêmeos, que encontram seu lugar no órgão correspondente e se integram a ele. No caso particular das gônadas, quando o ovário primitivo de um embrião fêmea é colonizado por algumas células gonodais de seu gêmeo macho, essas células expressam o gene SRY, o que fará com que essa região da gônada se diferencie como testículo. Como resultado, se desenvolve um ovo-testículo (com maior ou menor proporção de tecido testicular dependendo do grau de colonização da gônada em formação por células provenientes do gêmeo macho). Ademais, ao haver certa quantidade de tecido testicular produtor de MIH, circularão sobre o feto fêmea níveis desse hormônio que, embora baixos, afetarão o desenvolvimento normal dos dutos de Müller, fazendo com que as bezerras Freemartin possuam genitálias internas ausentes ou pouco desenvolvidas. Os andrógenos produzidos pelas zonas de tecido testicular, por fim, são suficientes para causar um certo grau de masculinização, que se manifesta como um clitóris mais grande que o normal ou um desenvolvimento corporal masculinizado. -/- REFERÊNCIAS BIBLIOGRÁFICAS -/- ARNOLD, Arthur P.; CHEN, Xuqi; ITOH, Yuichiro. What a difference an X or Y makes: sex chromosomes, gene dose, and epigenetics in sexual differentiation. In: Sex and gender differences in pharmacology. Springer, Berlin, Heidelberg, 2013. p. 67-88. CUNNINGHAM, James. Tratado de fisiologia veterinária. Elsevier Health Sciences, 2011. DERIVAUX, Jules; BARNABÉ, Renato Campanarut. Reprodução dos animais domésticos. Zaragoza: Acribia, 1980. DA SILVA, Emanuel Isaque Cordeiro. Desenvolvimento Embrionário e Diferenciação Sexual nos Animais Domésticos. Disponível em:. Acesso em: Julho de 2020. HAFEZ, Elsayed Saad Eldin; HAFEZ, Bahaa. Reprodução animal. São Paulo: Manole, 2004. HIDALGO, C. Galina et al. Reproducción de animales domésticos. México: Limusa, 2008. MACLAUGHLIN, David T.; DONAHOE, Patricia K. Sex determination and differentiation. New England Journal of Medicine, v. 350, n. 4, p. 367-378, 2004. MCCARTHY, Margaret M.; ARNOLD, Arthur P. Reframing sexual differentiation of the brain. Nature neuroscience, v. 14, n. 6, p. 677, 2011. PLANT, Tony M.; ZELEZNIK, Anthony J. (Ed.). Knobil and Neill's physiology of reproduction. Academic Press, 2014. REY, Rodolfo. Diferenciación sexual embrio-fetal: De las moléculas a la anatomía. Revista chilena de anatomía, v. 19, n. 1, p. 75-82, 2001. SENGER, P. L. Embryogenesis of the pituitary gland and male or female reproductive system. In. Pathways to Pregnancy and Parturition. Current Conception Inc, v. 1, p. 8-76, 1997. ZARCO, L. Diferenciación sexual. In. PORTA, L. R.; MEDRANO, J. H. H. Fisiología reproductiva de los animales domésticos. Cidade do México: FMVZ-UNAM, 2018. -/- REALIZAÇÃO -/- . (shrink)

Abstract: Alzheimer's disease (AD) is one of the most common types of dementia. Symptoms appear gradually and end with severe brain damage. People with Alzheimer's disease lose the abilities of knowledge, memory, language and learning. Recently, the classification and diagnosis of diseases using deep learning has emerged as an active topic covering a wide range of applications. This paper proposes examining abnormalities in brain structures and detecting cases of Alzheimer's disease especially in the early stages, using features (...) derived from medical images. The entire brain image was passed on through the transmission of Xception learning architectures. The Convolutional Neural Network (CNN) was constructed with the help of separable convolution layers that It can automatically learn general features from imaging data for classification. (shrink)

continent. 1.1 : 3-13. / 0/ – Introduction I want to propose, as a trajectory into the philosophically weird, an absurd theoretical claim and pursue it, or perhaps more accurately, construct it as I point to it, collecting the ground work behind me like the Perpetual Train from China Mieville's Iron Council which puts down track as it moves reclaiming it along the way. The strange trajectory is the following: Kant's critical philosophy and much of continental philosophy which has followed, (...) has been a defense against horror and madness. Kant's prohibition on speculative metaphysics such as dogmatic metaphysics and transcendental realism, on thinking beyond the imposition of transcendental and moral constraints, has been challenged by numerous figures proceeding him. One of the more interesting critiques of Kant comes from the mad black Deleuzianism of Nick Land stating, “Kant’s critical philosophy is the most elaborate fit of panic in the history of the Earth.” And while Alain Badiou would certainly be opposed to the libidinal investments of Land's Deleuzo-Guattarian thought, he is likewise critical of Kant's normative thought-bureaucracies: Kant is the one author for whom I cannot feel any kinship. Everything in him exasperates me, above all his legalism—always asking Quid Juris? Or ‘Haven’t you crossed the limit?’—combined, as in today’s United States, with a religiosity that is all the more dismal in that it is both omnipresent and vague. The critical machinery he set up has enduringly poisoned philosophy, while giving great succour to the academy, which loves nothing more than to rap the knuckles of the overambitious [….] That is how I understand the truth of Monique David-Menard’s reflections on the properly psychotic origins of Kantianism. I am persuaded that the whole of the critical enterprise is set up to to shield against the tempting symptom represented by the seer Swedenborg, or against ‘diseases of the head’, as Kant puts it. An entire nexus of the limits of reason and philosophy are set up here, namely that the critical philosophy not only defends thought from madness, philosophy from madness, and philosophy from itself, but that philosophy following the advent of the critical enterprise philosophy becomes auto-vampiric; feeding on itself to support the academy. Following Francois Laruelle's non-philosophical indictment of philosophy, we could go one step further and say that philosophy operates on the material of what is philosophizable and not the material of the external world. [1] Beyond this, the Kantian scheme of nestling human thinking between our limited empirical powers and transcendental guarantees of categorical coherence, forms of thinking which stretch beyond either appear illegitimate, thereby liquefying both pre-critical metaphysics and the ravings of the mad in the same critical acid. In rejecting the Kantian apparatus we are left with two entities – an unsure relation of thought to reality where thought is susceptible to internal and external breakdown and a reality with an uncertain sense of stability. These two strands will be pursued, against the sane-seal of post-Kantian philosophy by engaging the work of weird fiction authors H.P. Lovecraft and Thomas Ligotti. The absolute inhumanism of the formers universe will be used to describe a Shoggothic Materialism while the dream worlds of the latter will articulate the mad speculation of a Ventriloquil Idealism. But first we must address the relation of philosophy to madness as well as philosophy to weird fiction. /1/ – Philosophy and Madness There is nothing that the madness of men invents which is not either nature made manifest or nature restored. Michel Foucault. Madness and Civilization. The moment I doubt whether an event that I recall actually took place, I bring the suspicion of madness upon myself: unless I am uncertain as to whether it was not a mere dream. Arthur Schopenhauer. The World as Will and Idea, Vol. 3. Madness is commonly thought of as moving through several well known cultural-historical shifts from madness as a demonic or otherwise theological force, to rationalization, to medicalization psychiatric and otherwise. Foucault's Madness and Civilization is well known for orientating madness as a form of exclusionary social control which operated by demarcating madness from reason. Yet Foucault points to the possibility of madness as the necessity of nature at least prior to the crushing weight of the church. Kant’s philosophy as a response to madness is grounded by his humanizing of madness itself. As Adrian Johnston points out in the early pages of Time Driven pre-Kantian madness meant humans were seized by demonic or angelic forces whereas Kantian madness became one of being too human. Madness becomes internalized, the external demonic forces become flaws of the individual mind. Foucault argues that, while madness is de-demonized it is also dehumanized during the Renaissance, as madmen become creatures neither diabolic nor totally human reduced to the zero degree of humanity. It is immediately clear why for Kant, speculative metaphysics must be curbed – with the problem of internal madness and without the external safeguards of transcendental conditions, there is nothing to formally separate the speculative capacities for metaphysical diagnosis from the mad ramblings of the insane mind – both equally fall outside the realm of practicality and quotidian experience. David-Menard's work is particularly useful in diagnosing the relation of thought and madness in Kant's texts. David-Menard argues that in Kant's relatively unknown “An Essay on the Maladies of the Mind” as well as his later discussion of the Seer of Swedenborg, that Kant formulates madness primarily in terms of sensory upheaval or other hallucinatory theaters. She writes: “madness is an organization of thought. It is made possible by the ambiguity of the normal relation between the imaginary and the perceived, whether this pertains to the order of sensation or to the relations between our ideas” Kant's fascination with the Seer forces Kant between the pincers of “aesthetic reconciliation” – namely melancholic withdrawal – and “a philosophical invention” – namely the critical project. Deleuze and Guattari's schizoanalysis is a combination and reversal of Kant's split, where an aesthetic over engagement with the world entails prolific conceptual invention. Their embrace of madness, however, is of course itself conceptual despite all their rhizomatic maneuvers. Though they move with the energy of madness, Deleuze and Guattari save the capacity of thought from the fangs of insanity by imbuing materiality itself with the capacity for thought. Or, as Ray Brassier puts it, “Deleuze insists, it is necessary to absolutize the immanence of this world in such a way as to dissolve the transcendent disjunction between things as we know them and as they are in themselves”. That is, whereas Kant relied on the faculty of judgment to divide representation from objectivity Deleuze attempts to flatten the whole economy beneath the juggernaut of ontological univocity. Speculation, as a particularly useful form of madness, might fall close to Deleuze and Guattari’s shaping of philosophy into a concept producing machine but is different in that it is potentially self destructive – less reliant on the stability of its own concepts and more adherent to exposing a particular horrifying swath of reality. Speculative madness is always a potential disaster in that it acknowledges little more than its own speculative power with the hope that the gibbering of at least a handful of hysterical brains will be useful. Pre-critical metaphysics amounts to madness, though this may be because the world itself is mad while new attempts at speculative metaphysics, at post-Kantian pre-critical metaphysics, are well aware of our own madness. Without the sobriety of the principle of sufficient reason we have a world of neon madness: “we would have to conceive what our life would be if all the movements of the earth, all the noises of the earth, all the smells, the tastes, all the light – of the earth and elsewhere, came to us in a moment, in an instant – like an atrocious screaming tumult of things”. Speculative thought may be participatory in the screaming tumult of the world or, worse yet, may produce its spectral double. Against theology or reason or simply commonsense, the speculative becomes heretical. Speculation, as the cognitive extension of the horrorific sublime should be met with melancholic detachment. Whereas Kant's theoretical invention, or productivity of thought, is self -sabotaging, since the advent of the critical project is a productivity of thought which then delimits the engine of thought at large either in dogmatic gestures or non-systematizable empirical wondrousness. The former is celebrated by the fiction of Thomas Ligotti whereas the latter is espoused by the tales of H.P. Lovecraft. /2/ – Weird Fiction and Philosophy. Supernatural horror, in all its eerie constructions, enables a reader to taste treats inconsistent with his personal welfare. Thomas Ligotti Songs of a Dead Dreamer. I choose weird stories because they suit my inclination best—one of my strongest and most persistent wishes being to achieve,momentarily, the illusion of some strange suspension or violation of the galling limitations of time, space, and natural law which forever imprison us and frustrate our curiosity about the infinite cosmic spaces beyond the radius of our sight and analysis H.P. Lovecraft. “Notes on Writing Weird Fiction” Lovecraft states that his creation of a story is to suspend natural law yet, at the same time, he indexes the tenuousness of such laws, suggesting the vast possibilities of the cosmic. The tension that Lovecraft sets up between his own fictions and the universe or nature is reproduced within his fictions in the common theme of the unreliable narrator; unreliable precisely because they are either mad or what they have witnessed questions the bounds of material reality. In “The Call of Cthulhu” Lovecraft writes: The most merciful thing in the world, I think, is the inability of the human mind to correlate all its contents. We live on a placid island of ignorance in the midst of black seas of infinity, and it was not meant that we should voyage far. The sciences, each straining in its own direction, have hitherto harmed us little; but some day the piecing together of dissociated knowledge will open up such terrifying vistas of reality, and of our frightful position therein, that we shall either go mad from the revelation or flee from the deadly light into the peace and safety of a new dark age. Despite Lovecraft's invocations of illusion, he is not claiming that his fantastic creations such as the Old Ones are supernatural but, following Joshi, are only ever supernormal. One can immediately see that instead of nullifying realism Lovecraft in fact opens up the real to an unbearable degree. In various letters and non-fictional statements Lovecraft espoused strictly materialist tenets, ones which he borrowed from Hugh Elliot namely the uniformity of law, the denial of teleology and the denial of non-material existence. Lovecraft seeks to explore the possibilities of such a universe by piling horror upon horror until the fragile brain which attempts to grasp it fractures. This may be why philosophy has largely ignored weird fiction – while Deleuze and Guattari mark the turn towards weird fiction and Lovecraft in particular, with the precursors to speculative realism as well as contemporary related thinkers have begun to view Lovecraft as making philosophical contributions. Lovecraft's own relation to philosophy is largely critical while celebrating Nietzsche and Schopenhauer. This relationship of Lovecraft to philosophy and philosophy to Lovecraft is coupled with Lovecraft's habit of mercilessly destroying the philosopher and the figure of the academic more generally in his work, a destruction which is both an epistemological destruction and an ontological destruction. Thomas Ligotti's weird fiction which he has designated as a kind of “confrontational escapism” might be best described in the following quote from one of his shortstories, “The human phenomenon is but the sum of densely coiled layers of illusion each of which winds itself on the supreme insanity. That there are persons of any kind when all there can be is mindless mirrors laughing and screaming as they parade about in an endless dream”. Whereas Lovecraft's weirdness draws predominantly from the abyssal depths of the uncharted universe, Ligotti's existential horror focuses on the awful proliferation of meaningless surfaces that is, the banal and every day function of representation. In an interview, Ligotti states: We don't even know what the world is like except through our sense organs, which are provably inadequate. It's no less the case with our brains. Our whole lives are motored along by forces we cannot know and perceptions that are faulty. We sometimes hear people say that they're not feeling themselves. Well, who or what do they feel like then? This is not to say that Ligotti sees nothing beneath the surface but that there is only darkness or blackness behind it, whether that surface is on the cosmological level or the personal. By addressing the implicit and explicit philosophical issues in Ligotti's work we will see that his nightmarish take on reality is a form of malevolent idealism, an idealism which is grounded in a real, albeit dark and obscure materiality. If Ligotti's horrors ultimately circle around mad perceptions which degrade the subject, it takes aim at the vast majority of the focus of continental philosophy. While Lovecraft's acidic materialism clearly assaults any romantic concept of being from the outside, Ligotti attacks consciousness from the inside: Just a little doubt slipped into the mind, a little trickle of suspicion in the bloodstream, and all those eyes of ours, one by one, open up to the world and see its horror [...] Not even the solar brilliance of a summer day will harbor you from horror. For horror eats the light and digests it into darkness. Clearly, the weird fiction of Lovecraft and Ligotti amount to a anti-anthrocentric onslaught against the ramparts of correlationist continental philosophy. /3/ – Shoggothic Materialism or the Formless Formless protoplasm able to mock and reflect all forms and organs and processes—viscous agglutinations of bubbling cells—rubbery fifteen-foot spheroids infinitely plastic and ductile—slaves of suggestion, builders of cities—more and more sullen, more and more intelligent, more and more amphibious, more and more imitative—Great God! What madness made even those blasphemous Old Ones willing to use and to carve such things? H.P. Lovecraft. “At the Mountains of Madness” On the other hand, affirming that the universe resembles nothing and is only formless amounts to saying that the universe is something like a spider or spit. Georges Bataille. “Formless”. The Shoggoths feature most prominently in H.P. Lovecraft's shortstory “At the Mountains of Madness” where they are described in the following manner: It was a terrible, indescribable thing vaster than any subway train – a shapeless congeries of protoplasmic bubbles, faintly self -luminous, and with myriads of temporary eyes forming and un-forming as pustules of greenish light all over the tunnel-filling front that bore down upon us, crushing the frantic penguins and slithering over the glistening floor that it and its kind had swept so evilly free of all litter. The term is a litmus test for materialism itself as the Shoggoth is an amorphous creature. The Shoggoths were living digging machines bio engineered by the Elder Things, and their protoplasmic bodies being formed into various tools by their hypnotic powers. The Shoggoths eventually became self aware and rose up against their masters in an ultimately failed rebellion. After the Elder Ones retreated into the oceans leaving the Shoggoths to roam the frozen wastes of the Antarctic. The onto-genesis of the Shoggoths and their gross materiality, index the horrifyingly deep time of the earth a concept near and dear to Lovecraft's formulation of horror as well as the fear of intelligences far beyond, and far before, the ascent of humankind on earth and elsewhere. The sickly amorphous nature of the Shoggoths invade materialism at large, where while materiality is unmistakably real ie not discursive, psychological, or otherwise overly subjectivist, it questions the relation of materialism to life. As Eugene Thacker writes: The Shoggoths or Elder Things do not even share the same reality with the human beings who encounter them—and yet this encounter takes place, though in a strange no-place that is neither quite that of the phenomenal world of the human subject or the noumenal world of an external reality. Amorphous yet definitively material beings are a constant in Lovecraft's tales. In his tale “The Dream-Quest of Unknown Kadatth” Lovecraft describes Azathoth as, “that shocking final peril which gibbers unmentionably outside the ordered universe,” that, “last amorphous blight of nethermost confusion which blashphemes and bubbles at the centre of all infinity,” who, “gnaws hungrily in inconceivable, unlighted chambers beyond time”. Azathoth's name may have multiple origins but the most striking is the alchemy term azoth which is both a cohesive agent and a acidic creation pointing back to the generative and the decayed. The indistinction of generation and degradation materially mirrors the blur between the natural and the unnatural as well as life and non-life. Lovecraft speaks of the tension between the natural and the unnatural is his short story “The Unnameable.” He writes, “if the psychic emanations of human creatures be grotesque distortions, what coherent representation could express or portray so gibbous and infamous a nebulousity as the spectre of a malign, chaotic perversion, itself a morbid blasphemy against Nature?”. Lovecraft explores exactly the tension outlined at the beginning of this chapter, between life and thought. At the end of his short tale Lovecraft compounds the problem as the unnameable is described as “a gelatin—a slime—yet it had shapes, a thousand shapes of horror beyond all memory”. Deleuze suggests that becoming-animal is operative throughout Lovecraft's work, where narrators feel themselves reeling at their becoming non-human or of being the anomalous or of becoming atomized. Following Eugene Thacker however, it may be far more accurate to say that Lovecraft's tales exhibit not a becoming-animal but a becoming-creature. Where the monstrous breaks the purportedly fixed laws of nature, the creature is far more ontologically ambiguous. The nameless thing is an altogether different horizon for thought. The creature is either less than animal or more than animal – its becoming is too strange for animal categories and indexes the slow march of thought towards the bizarre. This strangeness is, as aways, some indefinite swirling in the category of immanence and becoming. Bataille begins “The Labyrinth” with the assertion that being, to continue to be, is becoming. More becoming means more being hence the assertion that Bataille's barking dog is more than the sponge. This would mean that the Shoggotth is altogether too much being, too much material in the materialism. Bataille suggests that there is an immanence between the eater and the eaten, across the species and never within them. That is, despite the chaotic storm of immanence there must remain some capacity to distinguish the gradients of becoming without reliance upon, or at least total dependence upon, the powers of intellection to parse the universe into recognizable bits, properly digestible factoids. That is, if we undo Deleuze's aforementioned valorization of sense which, for his variation of materialism, performed the work of the transcendental, but refuse to reinstate Kant's transcendental disjunction between thing and appearance, then it must be a quality of becoming-as-being itself which can account for the discernible nature of things by sense. In an interview with Peter Gratton, Jane Bennett formulates the problem thusly: What is this strange systematicity proper to a world of Becoming? What, for example, initiates this congealing that will undo itself? Is it possible to identify phases within this formativity, plateaus of differentiation? If so, do the phases/plateaus follow a temporal sequence? Or, does the process of formation inside Becoming require us to theorize a non-chronological kind of time? I think that your student’s question: “How can we account for something like iterable structures in an assemblage theory?” is exactly the right question. Philosophy has erred too far on the side of the subject in the subject-object relation and has furthermore, lost the very weirdness of the non-human. Beyond this, the madness of thought need not override. /4/ - Ventriloquial Idealism or the Externality of Thought My aim is the opposite of Lovecraft's. He had an appreciation for natural scenery on earth and wanted to reach beyond the visible in the universe. I have no appreciation for natural scenery and want the objective universe to be a reflection of a character. Thomas Ligotti. “Devotees of Decay and Desolation.” Unless life is a dream, nothing makes sense. For as a reality, it is a rank failure [….] Horror is more real than we are. Thomas Ligotti. “Professor Nobody's Little Lectures on Supernatural Horror”. Thomas Ligotti's tales are rife with mannequins, puppets, and other brainless entities which of replace the valorized subject of philosophy – that of the free thinking human being. His tales such as “The Dream of the Manikin” aim to destroy the rootedness of consciousness. James Trafford has connected the anti-egoism of Ligotti to Thomas Metzinger – where the self is at best an illusion and we plead desperately for someone else to acknowledge that we are real. Trafford has stated it thus, “Life is played out as an inescapable puppet show, an endless dream in which the puppets are generally unaware that they are trapped within a mesmeric dance of whose mechanisms they know nothing and over which they have no control”. An absolute materialism, for Ligotti, implies an alienation of the idea which leads to a ventriloquil idealism. As Ligotti notes in an interview, “the fiasco and nightmare of existence, the particular fiasco and nightmare of human existence, the sense that people are puppets of powers they cannot comprehend, etc.” And then further elaborates that,“[a]ssuming that anything has to exist, my perfect world would be one in which everyone has experienced the annulment of his or her ego. That is, our consciousness of ourselves as unique individuals would entirely disappear”. The externality of the idea leads to the unfortunate consequence of consciousness eating at itself through horror which, for Ligotti, is more real than reality and goes beyond horror-as-affect. Beyond this, taking together with the unreality of life and the ventriloquizing of subjectivity, Ligotti's thought becomes an idealism in which thought itself is alien and ultimately horrifying. The role of human thought and the relation of non-relation of horror to thought is not completely clear in Ligotti's The Conspiracy Against the Human Race. Ligotti argues in his The Conspiracy Against the Human Race,that the advent of thought is a mistake of nature and that horror is being in the sense that horror results from knowing too much. Yet, at the same time, Ligotti seems to suggest that thought separates us from nature whereas, for Lovecraft, thought is far less privileged – mind is just another manifestation of the vital principal, it is just another materialization of energy. In his brilliant “Prospects for Post-Copernican Dogmatism” Iain Grant rallies against the negative definition of dogmatism and the transcendental, and suggests that negatively defining both over-focuses on conditions of access and subjectivism at the expense of the real or nature. With Schelling, who is Grant's champion against the subjectivist bastions of both Fichte and Kant, Ligotti's idealism could be taken as a transcendental realism following from an ontological realism. Yet the transcendental status of Ligotti's thought move towards a treatment of the transcendental which may threaten to leave beyond its realist ground. Ligotti states: Belief in the supernatural is only superstition. That said, a sense of the supernatural, as Conrad evidenced in Heart of Darkness, must be admitted if one's inclination is to go to the limits of horror. It is the sense of what should not be- the sense of being ravaged by the impossible. Phenomenally speaking, the super-natural may be regarded as the metaphysical counterpart of insanity, a transcendental correlative of a mind that has been driven mad. Again, Ligotti equates madness with thought, qualifying both as supernatural while remaining less emphatic about the metaphysical dimensions of horror. The question becomes one of how exactly the hallucinatory realm of the ideal relates to the black churning matter of Lovecraft's chaos of elementary particles. In his tale “I Have a Special Plan for This World” Ligotti formulates thus: A: There is no grand scheme of things. B: If there were a grand scheme of things, the fact – the fact – that we are not equipped to perceive it, either by natural or supernatural means, is a nightmarish obscenity. C: The very notion of a grand scheme of things is a nightmarish obscenity. Here Ligotti is not discounting metaphysics but implying that if it does exist the fact that we are phenomenologically ill-equipped to perceive that it is nightmarish. For Ligotti, nightmare and horror occur within the circuit of consciousness whereas for Lovecraft the relation between reality and mind is less productive on the side of mind. It is easier to ascertain how the Kantian philosophy is a defense against the diseases of the head as Kant armors his critical enterprise from too much of the world and too much of the mind. The weird fiction of both Lovecraft and Ligotti demonstrates that there is too much of both feeding into one another in a way that corrodes the Kantian schema throughly, breaking it down into a dead but still ontologically potentiated nigredo. The haunting, terrifying fact of Ligotti's idealism is that the transcendental motion which brought thought to matter, while throughly material and naturalized, brings with it the horror that thought cannot be undone without ending the material that bears it either locally or completely. Thought comes from an elsewhere and an elsewhen being-in-thought. The unthinkable outside thought is as maddening as the unthought engine of thought itself within thought which doesn't exist except for the mind, the rotting décor of the brain. /5/ - Hyperstitional Transcendental Paranoia or Self -Expelled Thought Weird fiction has been given some direct treatment in philosophy in the mad black Deleuzianism of Nick Land. Nick Land along with others in the 1990s created the Cyber Culture Research Unit as well as the research group Hyperstition. The now defunct hyperstitional website, an outgrowth of the Cyber Culture Research Unit, defined hyperstition in the following fourfold: 1-Element of effective culture that makes itself real. 2-Fictional quantity functional as a time-traveling device. 3-Coincidence intensifier. 4-Call to the Old Ones. The distinctively Lovecraftian character of hyperstition is hard to miss as is its Deleuzo-Guattarian roots. In the opening pages of A Thousand Plateaus Deleuze and Guattari write, “We have been criticized for over-quoting literary authors. But when one writes, the only question is which other machine the literary machine can be plugged into”. The indisinction of literature and philosophy mirrors the mess of being and knowing as post-correlationist philosophy, where philosophy tries to make itself real where literature, especially the weird, aims itself at the brain-circuit of horror. The texts of both Lovecraft and Ligotti work through horror as epistemological plasticity meeting with proximity as well as the deep time of Lovecraft and the glacially slow time of paranoia in Ligotti. Against Deleuze, and following Brassier, we cannot allow the time of consciousness, the Bergsonian time of the duree, to override natural time, but instead acknowledge that it is an unfortunate fact of existence as a thinking being. Horror-time, the time of consciousness, with all its punctuated moments and drawn out terrors, cannot compare to the deep time of non-existence both in the unreachable past and the unknown future. The crystalline cogs of Kant's account of experience as the leading light for the possibility of metaphysics must be throughly obliterated. His gloss of experience in Prolegomena to any Future Metaphysics could not be more sterile: Experience consists of intuitions, which belong to the sensibility, and of judgments, which are entirely a work of the understanding. But the judgments which the understanding makes entirely out of sensuous intuitions are far from being judgments of experience. For in the one case the judgment connects only the perceptions as they are given in sensuous intuition [....] Experience consists in the synthetic connection of appearances in consciousness, so far as this connection is necessary. Here it is difficult to dismiss the queasiness that Kant's legalism induces upon sight for both Badiou and David-Menard. Kant's thought becomes, as Foucault says when reflecting on Sade's text in relation to nature, “the savage abolition of itself”. For Badiou, Kant's philosophy simply closes off too much of the outside, freezing the world of thought in an all too limited formalism. Critical philosophy is simply the systematized quarantine on future thinking, on thinking which would threaten the formalism which artificially grants thought its own coherency in the face of madness. Even the becoming-mad of Deleuze, while escaping the rumbling ground, makes grounds for itself, mad grounds but grounds which are thinkable in their affect. The field of effects allows for Deleuze's aesthetic and radical empiricism, in which effects and/or occasions make up the material of the world to be thought as a chaosmosis of simulacra. Given a critique of an empiricism of aesthetics, of the image, it may be difficult to justify an attack on Kantian formalism with the madness of literature, which does not aim to make itself real but which we may attempt to make real. That is, how do Lovecraft's and Ligotti's materials, as materials for philosophy to work on, differ from either the operative formalisms of Kant or the implicitly formalized images of Deleuzian empiricism? It is simply that such texts do not aim to make themselves real, and make claims to the real which are more alien to us than familiar, which is why their horror is immediately more trustworthy. This is the madness which Blanchot discusses in The Infinite Conversation through Cervantes and his knight – the madness of book-life, of the perverse unity of literature and life a discussion which culminates in the discussion of one of the weird's masters, that of Kafka. The text is the knowing of madness, since madness, in its moment of becoming-more-mad, cannot be frozen in place but by the solidifications of externalizing production. This is why Foucault ends his famous study with works of art. Furthermore extilligence, the ability to export the products of our maligned brains, is the companion of the attempts to export, or discover the possibility of intelligences outside of our heads, in order for philosophy to survive the solar catastrophe. To borrow again from Deleuze, writing is inseparable from becoming. The mistake is to believe that madness is reabsorbed by extilligence, by great works, or that it could be exorcised by the expelling of thought into the inorganic or differently organic. Going out of our heads does not guarantee we will no longer mean we cannot still go out of our minds. This is simply because of the outside, of matter, or force, or energy, or thing-in-itself, or Schopenhauerian Will. In Lovecraft’s “The Music of Erich Zahn” an “impoverished student of metaphysics” becomes intrigued by strange viol music coming from above his room. After meeting the musician the student discovers that each night he plays frantic music at a window in order to keep some horridness at bay, some “impenetrable darkness with chaos and pandemonium”. The aesthetic defenses provided by the well trained brain can bear the hex of matter for so long, the specter of unalterability within it which too many minds obliterate, collapsing everything before the thought of thought as thinkable or at least noetically mutable on our own terms. Transcendental paranoia is the concurrent nightmare and promise of Paul Humphrey's work, of being literally out of our minds. It is the gothic counterpart of thinking non-conceptually but also of thinking never belonging to any instance of purportedly solid being. As Bataille stated, “At the boundary of that which escapes cohesion, he who reflects within cohesion realizes there is no longer any room for him” Thought is immaterial only to the degree that it is inhuman, it is a power that tries, always with failure, to ascertain its own genesis. Philosophy, if it can truly return to the great outdoors, if it can leave behind the dead loop of the human skull, must recognize not only the non-priority of human thought, but that thought never belongs to the brain that thinks it, thought comes from somewhere else. To return to the train image from the beginning “a locomotive rolling on the surface of the earth is the image of continuous metamorphosis” this is the problem of thought, and of thinking thought, of being no longer able to isolate thought, with only a thought-formed structure. [1] One of the central tenets of Francois Laruelle's non-philosophy is that philosophy has traditionally operated on material already presupposed as thinkable instead of trying to think the real in itself. Philosophy, according to Laruelle, remains fixated on transcendental synthesis which shatters immanence into an empirical datum and an a prori factum which are then fused by a third thing such as the ego. For a critical account of Laruelle's non-philosophy see Ray Brassier's Nihil Unbound. (shrink)

The article discusses the actual problem of social support for people with mental health problems, which has an important place in the study field of social psychology and social work.The article also deals with the definition of the concept of “mental health”, the problem of introducing the term “mental health problems” as a way to avoid stigmatization, and the spread of a humanistic attitude to persons with a psychiatric diagnosis. It also discussed modern theoretical approaches that offer an understanding (...) of the contribution of biological, social, and psychological factors into the cause of mental health problems. -/- The problem of mental illness is common to all countries of the world, as WHO data evidenced the number of people with mental disorders among the world’s population, ranging from 4–5 %. According to researchers P. Voloshin and N. Maruta, the spread of mental and behavioral disorders in Ukraine is characterized by a slow increase of about 2.9 % in every 10 years. Researchers argue that in subsequent years, according to the prognostic data, there will be an increase in these indicators. The issue of providing social support to people with PDS in Ukrainian society is very relevant, which is complicated by their social isolation in the process of recovery after the treatment. The results of scientific research in the context of different cultures and relatively diverse life events (hospitalization, mental illness, unemployment, old age) generally confirm the positive results of using social support to promote mental and physical health. Instead, there are no studies in Ukrainian science related to the phenomenon of social support of people with mental health problems. -/- It is important to define the concepts of “mental health” and “mental health problems” in the process of studying the features of social support for people with mental health problems. The term “mental health” combines the medical and psychological fields of science and practice, but modern psychology offers a comprehensive approach to assessing the psychological health of a person, the psychological norm, its limits, taking into account the criteria of mental health. The description of the mental health given by the Psychological Dictionary points out the components of awareness and the sense of continuity, continuity and identity of their physical and mental “I”; sense of continuity and identity of experiences in similar situations; critical to yourself and your mental activity and its results; the adequacy of psychic reactions of force and frequency of environmental influences; the ability to manage their behavior in accordance with social norms; planning personal activities and implementing them; changing the way of behavior depending on the changing circumstances of life. -/- The concept of “mental health problem” was taken as a term that denotes all the symptoms classified in ICD-10 and DSM-IV, which are recommended by experts to clients for appropriate treatment and care. Scientists and mental health practitioners point out that mental health problems can affect the way an individual thinks, feels, and behaves; affects self-service, fulfills professional duties, social, family roles, and household behavior, which is usually deeply affected by the quality of life of the individual. Numerous results of the research show that there are specific psychological and personality factors apart from the biological causes of mental disorders (genetic factors that contribute to the imbalance of chemicals in the brain) that make people vulnerable to occurrences of the mental health problems. -/- Several modern theoretical approaches offer an understanding of the contribution of biological, social, and psychological factors to the induction of mental health problems: the traditional medical model, the rehabilitation model, the interface model, the social model, and the biopsychosocial approach. Only biopsychosocial and social models are consistent with the definition of WHO disability and emphasize the impact social aspects of mental health and the quality of life of people with mental health problems. -/- Individuals with PPP, as a social community, have specific needs that differentiate them from other members of society, one of which is the need for constant socio-psychological support. So, the contribution of psychology and social work to the quality of life of people with mental disorder lies in the application of professional approaches and methods based on the biopsychosocial (social) model, which emphasize the need for socio-psychological support. An example of such a technique is the model of modern social work practice “people-in-environment”, which serves as a guiding principle of social work and emphasizes the importance of understanding the persons with disorder and their behavior in the light of the multiple context of the social environment in which these persons live and act. Specialists of social work and psychology make interventions at three levels: individual, at the family level, and at the community level, by means of intensifying the support of the environment within the cognitive-behavioral and other approaches, which contribute to the process of reintegrating people with mental health problems into community. (shrink)

The idea of disease as an objective malfunctioning cannot be accepted for many different reasons. “Malfunctioning” or “failure” have a meaning only if the perfect working condition or normality is univocally determined. The differences between a person and any other person are not unimportant and cannot be ignored neither in diagnosis nor in treatment. These differences can be ascribable to three different sets of reasons: 1.illnesses leave irreversible marks on the organic structure, for they modify the information an organism (...) has at least as far as the neuroendocrine and immune systems are involved; 2.there are individual differences in the immune system; 3.there are individual differences in the functional organization of the brain that are not due only to biological causes. Furthermore the subjective perception of the illness itself must be included among the elements that determine the features of an illness. Notwithstanding the presence of the same symptoms and the same tests readings, two people may perceive their illness in a different way, with effects on the course of the illness itself and the effectiveness of the treatment. The idea of disease also depends on the cultural context. (shrink)

With the shortage of physicians and surgeons and increase in demand worldwide due to situations such as the COVID-19 pandemic, there is a growing interest in finding solutions to help address the problem. A solution to this problem would be to use neurotechnology to provide them augmented cognition, senses and action for optimal diagnosis and treatment. Consequently, doing so can negatively impact them and others. We argue that applying neurotechnology for human enhancement in physicians and surgeons can cause injustices, (...) and harm to them and patients. In this paper, we will first describe the augmentations and neurotechnologies that can be used to achieve the relevant augmentations for physicians and surgeons. We will then review selected ethical concerns discussed within literature, discuss the neuroengineering behind using neurotechnology for augmentation purposes, then conclude with an analysis on outcomes and ethical issues of implementing human augmentation via neurotechnology in medical and surgical practice. (shrink)

Reports of patients with schizophrenia show a fragmented and anomalous subjective experience. This pathological subjective experience, we suggest, can be related to the fact that disembodiment inhibits the possibility of intersubjective experience, and more importantly of common sense. In this paper, we ask how to investigate the anomalous experience both from qualitative and quantitative viewpoints. To our knowledge, few studies have focused on a clinical combination of both first- phenomenological assessment and third-person biological methods, especially for Schizophrenia, or ASD therapeutics (...) and diagnosis. We will thus attempt to bring forward a second-person scientific design, accounting for both the first-person subjective experiential aspects, and respective third-person neurobiological correlates of embodied aesthetics in anomalous experience. From this proposal, we further explore the consequences to clinical and research practice. (shrink)

Ontologies formally represent reality in a way that limits ambiguity and facilitates automated reasoning and data fusion, but is often daunting to the non-technical user. Thus, many researchers have endeavored to hide the formal syntax and semantics of ontologies behind the constructs of Controlled Natural Languages (CNLs), which retain the formal properties of ontologies while simultaneously presenting that information in a comprehensible natural language format. In this paper, we build upon previous work in this field by evaluating prospects of implementing (...) International Technology Alliance Controlled English (ITACE) as a middleware for ontology editing. We also discuss at length a prototype of a natural language conversational interface application designed to facilitate ontology editing via the formulation of CNL constructs. (shrink)

I argue that ductal carcinoma in situ (DCIS), the tumor most commonly diagnosed by breast mammography, cannot be confidently classified as cancer, that is, as pathological. This is because there may not be dysfunction present in DCIS—as I argue based on its high prevalence and the small amount of risk it conveys—and thus DCIS may not count as a disease by dysfunction-requiring approaches, such as Boorse’s biostatistical theory and Wakefield’s harmful dysfunction account. Patients should decide about treatment for DCIS (...) based on the risks it poses and the risks and benefits of treatment, not on its disease status. (shrink)

Deep brain stimulation has been of considerable interest to bioethicists, in large part because of the effects that the intervention can occasionally have on central features of the recipient’s personality. These effects raise questions regarding the philosophical concept of authenticity. In this article, we expand on our earlier work on the concept of authenticity in the context of deep brain stimulation by developing a diachronic, value-based account of authenticity. Our account draws on both existentialist and essentialist approaches to (...) authenticity, and Laura Waddell Ekstrom’s coherentist approach to personal autonomy. In developing our account, we respond to Sven Nyholm and Elizabeth O’Neill’s synchronic approach to authenticity, and explain how the diachronic approach we defend can have practical utility, contrary to Alexandre Erler and Tony Hope’s criticism of autonomy-based approaches to authenticity. Having drawn a distinction between the authenticity of an individual’s traits and the authenticity of that person’s values, we consider how our conception of authenticity applies to the context of anorexia nervosa in comparison to other prominent accounts of authenticity. We conclude with some reflections on the prudential value of authenticity, and by highlighting how the language of authenticity can be invoked to justify covert forms of paternalism that run contrary to the value of individuality that seems to be at the heart of authenticity. (shrink)

In clinical medicine, a diagnosis can offer an explanation of a patient's symptoms by specifying the pathology that is causing them. Diagnoses in psychiatry are also sometimes presented in clinical texts as if they pick out pathological processes that cause sets of symptoms. However, current evidence suggests the possibility that many diagnostic categories in psychiatry are highly causally heterogeneous. For example, major depressive disorder may not be associated with a single type of underlying pathological process, but with a range (...) of different causal pathways, each involving complex interactions of various biological, psychological, and social factors. This paper explores the implications of causal heterogeneity for whether psychiatric diagnoses can be said to serve causal explanatory roles in clinical practice. I argue that while they may fall short of picking out a specific cause of the patient's symptoms, they can nonetheless supply different sorts of clinically relevant causal information. In particular, I suggest that some psychiatric diagnoses provide negative information that rules out certain causes, some provide approximate or disjunctive information about the range of possible causal processes, and some provide causal information about the relations between the symptoms themselves. (shrink)

A diagnostic process is an investigative process that takes a clinical picture as input and outputs a diagnosis. We propose a method for distinguishing diagnoses that are warranted from those that are not, based on the cognitive processes of which they are the outputs. Processes designed and vetted to reliably produce correct diagnoses will output what we shall call ‘warranted diagnoses’. The latter are diagnoses that should be trusted even if they later turn out to have been wrong. Our (...) work is based on the recently developed Cognitive Process Ontology and further develops the Ontology of General Medical Science. It also has applications in fields such as intelligence, forensics, and predictive maintenance, all of which rely on vetted processes designed to secure the reliability of their outputs. (shrink)

A pressing need for interrater reliability in the diagnosis of mental disorders emerged during the mid-twentieth century, prompted in part by the development of diverse new treatments. The Diagnostic and Statistical Manual of Mental Disorders (DSM), third edition answered this need by introducing operationalized diagnostic criteria that were field-tested for interrater reliability. Unfortunately, the focus on reliability came at a time when the scientific understanding of mental disorders was embryonic and could not yield valid disease definitions. Based on accreting (...) problems with the current DSM-fourth edition (DSM-IV) classification, it is apparent that validity will not be achieved simply by refining criteria for existing disorders or by the addition of new disorders. Yet DSM-IV diagnostic criteria dominate thinking about mental disorders in clinical practice, research, treatment development, and law. As a result, the modernDSMsystem, intended to create a shared language, also creates epistemic blinders that impede progress toward valid diagnoses. Insights that are beginning to emerge from psychology, neuroscience, and genetics suggest possible strategies for moving forward. (shrink)

The potential to collect brain data more directly, with higher resolution, and in greater amounts has heightened worries about mental and brain privacy. In order to manage the risks to individuals posed by these privacy challenges, some have suggested codifying new privacy rights, including a right to “mental privacy.” In this paper, we consider these arguments and conclude that while neurotechnologies do raise significant privacy concerns, such concerns are—at least for now—no different from those raised by other well-understood (...) data collection technologies, such as gene sequencing tools and online surveillance. To better understand the privacy stakes of brain data, we suggest the use of a conceptual framework from information ethics, Helen Nissenbaum’s “contextual integrity” theory. To illustrate the importance of context, we examine neurotechnologies and the information flows they produce in three familiar contexts—healthcare and medical research, criminal justice, and consumer marketing. We argue that by emphasizing what is distinct about brain privacy issues, rather than what they share with other data privacy concerns, risks weakening broader efforts to enact more robust privacy law and policy. (shrink)

Definitive diagnosis of malaria requires the demonstration through laboratory tests of the presence within the patient of malaria parasites or their components. Since malaria parasites can be present even in the absence of malaria manifestations, and since symptoms of malaria can be manifested even in the absence of malaria parasites, malaria diagnosis raises important issues for the adequate understanding of disease, etiology and diagnosis. One approach to the resolution of these issues adopts a realist view, according to (...) which the needed clarifications will be derived from a careful representation of the entities on the side of the patient which form the ultimate truthmakers for clinical statements. We here address a challenge to this realist approach relating to the diagnosis of malaria, and show how this challenge can be resolved by appeal to Basic Formal Ontology (BFO) and to the Ontology for General Medical Science (OGMS) constructed in its terms. (shrink)

In this chapter, our focus is the role played by notions of rationality in the diagnosis of mental disorders, and in the practice of overriding patient autonomy in psychiatry. We describe and evaluate different hypotheses concerning the relationship between rationality and diagnosis, raising questions about what features underpin psychiatric categories. These questions reinforce widely held concerns about the use of diagnosis as a justification for overriding autonomy, which have motivated a shift to mental incapacity as an alternative (...) justification. However, this approach too has recently been criticized from a mental disability rights perspective. Our analysis of the relationship between mental capacity and rationality is used to illuminate these concerns, and to investigate further the relationship between rationality and psychiatric diagnosis. (shrink)

The relation between body and mind is one of the oldest riddles that has puzzled mankind. That material and mental events may interact is accepted even by the law: our mental capacity to concentrate on the task can be seriously reduced by drugs. Physical and chemical processes may act upon the mind; and when we are writing a difficult letter, our mind acts upon our body and, through a chain of physical events, upon the mind of the recipient of the (...) letter. This is what the authors of this book call the 'interaction of mental and physical events'. We know very little about this interaction; and according to recent philosophical fashions this is explained by the alleged fact that we have brains but no thoughts. The authors of this book stress that they cannot solve the body mind problem; but they hope that they have been able to shed new light on it. Eccles especially with his theory that the brain is a detector and amplifier; a theory that has given rise to important new developments, including new and exciting experiments; and Popper with his highly controversial theory of 'World 3'. They show that certain fashionable solutions which have been offered fail to understand the seriousness of the problems of the emergence of life, or consciousness and of the creativity of our minds. In Part I, Popper discusses the philosophical issue between dualist or even pluralist interaction on the one side, and materialism and parallelism on the other. There is also a historical review of these issues. In Part II, Eccles examines the mind from the neurological standpoint: the structure of the brain and its functional performance under normal as well as abnormal circumstances. The result is a radical and intriguing hypothesis on the interaction between mental events and detailed neurological occurrences in the cerebral cortex. Part III, based on twelve recorded conversations, reflects the exciting exchange between the authors as they attempt to come to terms with their opinions. (shrink)

The biophilosophic justification for the idea that “brain death” is death needs to support two claims: that what dies in human death is a human organism, not merely a psychological entity distinct from it; that total brain failure signifies the end of the human organism as a whole. Defenders of brain death typically assume without argument that the first claim is true and argue for the second by defending the “integrative unity” rationale. Yet the integrative unity rationale (...) has fallen on hard times. In this article, I give reasons for why we should think of ourselves as organisms, and why the “fundamental work” rationale put forward by the 2008 President’s Council is better than the integrative unity rationale, despite persistent objections to it. (shrink)

Background: Mint is a grassy, perennial plant, belonging to the oral platoon, fast growing and spreading, its leaves are green in color, fragrant, tart, refreshing, square-shaped leg, bifurcated, erect, ranging in height from (10 - 201 cm). Home to Europe and Asia. The mint plant has many benefits, the most important of which are pain relief, treatment of gallbladder disorders, the expulsion of gases, anti-inflammatory, and relaxing nerves. While the mint plant is the ideal option for the start of gardens, (...) it is prone to some common diseases that affect the plant's growth. Objectives: The main goal of this expert system is to get the appropriate diagnosis of disease and the correct treatment. Methods: In this paper, the design of the proposed Expert System was produced to help Farmers and those interested in agriculture in diagnosing many of the Mint diseases such as Mint rust, Verticillium wilt, Anthracnose, Powdery mildew, Black Stem Rot, Stem and stolon canker, Septoria leaf spot. The proposed expert system presents an overview of mint diseases are given, the cause of diseases outlined and the treatment of disease whenever possible is given out. CLIPS Expert System language was used for designing and implementing the proposed expert system. Results: The proposed Mint diseases diagnosis expert system was evaluated by Agricultural Students at AL Azhar University and some friends interested in agriculture and they were satisfied with its performance. Conclusions: The proposed expert system is very useful for Farmers and those interested in agriculture. (shrink)

In this paper I present an argument in favour of a parental duty to use preimplantation genetic diagnosis (PGD). I argue that if embryos created in vitro were able to decide for themselves in a rational manner, they would sometimes choose PGD as a method of selection. Couples, therefore, should respect their hypothetical choices on a principle similar to that of patient autonomy. My thesis shows that no matter which moral doctrine couples subscribe to, they ought to conduct the (...) PGD procedure in the situations when it is impossible to implant all of the created embryos and if there is a significant risk for giving birth to a child with a serious condition. (shrink)

The objective of the paper is to implement and validate diagnosis in the medical field via refined neutrosophic fuzzy logic (RNFL). As such, we have proposed a Max-Min composition (MMC) method in RNFL. This method deals with the diagnosis under certain constraints like uncertainty and indeterminacy. Further, we have considered the diagnosis problems to validate the sensitivity analysis of the novel multi attribute decision-making technique. Finally, we gave the graphical representations and compared the obtained results with other (...) existing measures in refined neutrosophic fuzzy sets. (shrink)

There is a strong philosophical intuition that direct study of the brain can and will constrain the development of psychological theory. When this intuition is tested against case studies on the neurophysiology and psychology of perception and memory, it turns out that psychology has led the way toward knowledge of neurophysiology. An abstract argument is developed to show that psychology can and must lead the way in neuroscientific study of mental function. The opposing intuition is based on mainly weak (...) arguments about the fundamentality or objectivity of physics or physiology in relation to psychology. -/- Philosophy of Science, Vol. 67, Supplement. Proceedings of the 1998 Biennial Meetings of the Philosophy of Science Association. Part II: Symposia Papers (Sep., 2000). (shrink)

The brain in its plasticity and inherent 'sociality' can be proclaimed and projected as a revolutionary organ. Far from the old reactions which opposed the authenticity of political theory and praxis to the dangerous naturalism of 'cognitive science' (with images of men in white coats, the RAND Corporation or military LSD experiments), recent decades have shown us some of the potentiality of the social brain (Vygotsky, and more recently Negri 1995 and Negri 2000, Virno 2001). Is the (...) class='Hi'>brain somehow inherently a utopian topos? If in some earlier papers I sought to defend naturalism against these reactions, here I consider a new challenge: the recently emerged disciplines of neuronormativity, which seek in their own way to overcome the nature-normativity divide. This is the task of a materialist brain theory today. 1. The setup: horns of a dilemma There is a lingering zone of what one might think of as sore cognitive muscle tissue in the area of materialism. It is an area of both contested territory and in some cases, a kind of pathos of distance of the 'Ugh! Keep that thing away from me!' sort. I have in mind the combination of materialism as an emancipatory socio-political project (which need not be construed in strictly Marx-Engels terms, if we think of Lucretius et al.) and as a cold-hearted 'spontaneous philosophy of the men in white coats', e.g. nefarious neurophilosophers. Faced with this rather massive alternative, this choice between two projects, I have stubbornly been saying since some discussions with Negri in the late 90s. (shrink)

In this paper, we engage in dialogue with Jonathan Pugh, Hannah Maslen, and Julian Savulescu about how to best interpret the potential impacts of deep brain stimulation on the self. We consider whether ordinary people’s convictions about the true self should be interpreted in essentialist or existentialist ways. Like Pugh et al., we argue that it is useful to understand the notion of the true self as having both essentialist and existentialist components. We also consider two ideas from existentialist (...) philosophy – Jean-Paul Sartre and Simone de Beauvoir’s ideas about “bad faith” and “ambiguity” – to argue that there can be value to patients in regarding themselves as having a certain amount of freedom to choose what aspects of themselves should be considered representative of their true selves. Lastly, we consider the case of an anorexia nervosa-patient who shifts between conflicting mind-sets. We argue that mind-sets in which it is easier for the patient and his or her family to share values can plausibly be considered to be more representative of the patient’s true self, if this promotes a well-functioning relationship between the patient and the family. However, we also argue that families are well-advised to give patients room to figure out what such shared values mean to them, since it can be alienating for patients if they feel that others try to impose values on them from the outside. (shrink)

In psychiatry some disorders of cognition are distinguished from instances of normal cognitive functioning and from other disorders in virtue of their surface features rather than in virtue of the underlying mechanisms responsible for their occurrence. Aetiological considerations often cannot play a significant classificatory and diagnostic role, because there is no sufficient knowledge or consensus about the causal history of many psychiatric disorders. Moreover, it is not always possible to uniquely identify a pathological behaviour as the symptom of a certain (...) disorder, as disorders that are likely to differ both in their causal histories and in their overall manifestations may give rise to very similar patterns of behaviour. -/- Consider delusions as an example. It wouldn’t be correct to define delusions as those beliefs people form as a result of a neurobiological deficit and a hypothesis-evaluation deficit (as some versions of the two-factor theory of delusions suggest), because for some delusions no neurobiological deficit may be found, and reasoning biases and motivational factors may be contributors to the formation of the delusion (e.g. McKay et al., 2005). Moreover, it would be a mistake to define delusions as symptoms of schizophrenia alone, because they occur also in other disorders, including dementia, amnesia, and delusional disorders. Thus, aetiological considerations may appear in the description and analysis of delusions, but do not feature prominently in their definition. -/- In this paper I argue that the surface features used as criteria for the classification and diagnosis of disorders of cognition are often epistemic in character. I shall offer two examples: confabulations and delusions are defined as beliefs or narratives that fail to meet standards of accuracy and justification. Although classifications and diagnoses based on features of people’s observable behaviour are necessary at these early stages of neuropsychiatric research, given the variety of conditions in which certain phenomena appear, I shall attempt to show that current epistemic accounts of confabulations and delusions have limitations. Epistemic criteria can guide both research and clinical practice, but fail to provide sufficient conditions for the identification of delusions and confabulations, and fail to demarcate pathological from non-pathological narratives or beliefs. -/- Another limitation of current epistemic accounts – which I shall not address here – is the excessive focus on epistemic faults of confabulations and delusions at the expense of their epistemically neutral or advantageous features (see Bortolotti and Cox, 2009). This may lead to a misconception of delusions and confabulations, and to an oversimplification in the assessment of the needs of people who require clinical treatment for their psychotic symptoms. (shrink)

The Japanese Transplantation Law is unique among others in that it allows us to choose between "brain death" and "traditional death" as our death. In every country 20 to 40 % of the popularion doubts the idea of brain death. This paper reconsiders the concept, and reports the ongoing rivision process of the current law. Published in Hastings Center Report, 2001.