Objective: to evaluate CANLPH score and systemic immune inflammation index (SII) in patients with symptomatic rheumatic mitral stenosis (MS) undergoing percutaneous mitral balloon valvuloplasty (PMBV). -/- Methods: 62 patients who underwent PMBV in our clinic between 2018 and 2021 were included retrospectively. The patients were divided into 2 groups according to echo score. The CANLPH score was calculated from the cut-off values of C-reactive protein to albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR) and platelet to (...) hemoglobin ratio (PHR), determined with the Youden index and SII by the formula platelet x neutrophil/lymphocyte. P <0.05 was considered statistically significant. -/- Results: The mean age of the patients was 44.5±10.4 years (40 female, 64.5%). The mean values of SII and CANLPH scores were higher in the Echo score >8 group (p <0.001, both). The mean mitral gradient before and after PMBV was 12.6±5.7mm Hg and 5.0±2.4 mm Hg, and the mean valve area was 1.12±0.27 cm2 and 1.85±0.29 cm2. A statistically significant and negative correlation was observed between the gradient decrease after the procedure and the CANLPH score and SII (r=-0.426, p=0.001 and r=-0.418, p=0.001, respectively). In receiver operating characteristic (ROC) curve analysis, it was concluded that the ability of CANPLH score to predict the higher Echo scores was noninferior to SII with an area under curve (AUC:0.820 (0.701-0.906) and AUC:0.786 (0.664-0.880), z statistics 0.576 and p=0.564. -/- Conclusion: SII and CANLPH scores are correlated with Echo score. A significant negative relationship was found with both biomarkers and gradient decrease after the PMBV. (shrink)

To enable microbial colonisation of the gut mucosa, the intestinal immune system must not only react to danger signals but also recognize cues that indicate safety. Safety recognition, paradoxically, is mediated by the same environmental sensors that are involved in signalling danger. Indeed, in addition to their well established role in inducing inflammation in response to stress signals, pattern recognition receptors (PRRs) and a variety of metabolic sensors also promote gut-microbiota symbiosis by responding to "microbial symbiosis factors", "resolution-associated (...) molecular patterns", markers of energy extraction and other signals indicating the absence of pathogenic infection and tissue damage. Here we focus on how the paradoxical role of immune receptors and other environmental sensors define the microbiota signature of the individual. (shrink)

The idea that the immune system distinguishes between self and non-self was one of the central assumptions of immunology in the second half of 20 th century. This idea influenced experimental design and data interpretation. However, in the face of new evidence there is a need for a new conceptual framework in immunology.

Coronavirus is a viral irresistible sickness brought about by SARS- COV2. Its clinical signs and side effects are on an expansive range going from asymptomatic to serious confusions like multi-organ disappointment, thromboembolism, and extreme pneumonia with respiratory disappointment. More awful results and higher death rates have been accounted for in the old, individuals with co-morbidities, and malnourished people. Sustenance is central to acceptable wellbeing and safe capacity. It frames an essential segment of therapy modalities for different intense and persistent infections, (...) particularly where a causative therapy isn't yet perceived. Despite the fact that reviews tending to the part of explicit supplements in COVID-19 are still at a beginning phase, accessible proof recommends that addressing the necessities of a variety of large scale and miniature supplements (energy, proteins, fats, nutrients A, D, E, C, B nutrients, iron, selenium, zinc, and so forth) Additionally, supplements are Immune System Might Promote Recovery for Mild COVID-19 Patients Impact of Coronavirus on Education in India Review 466 determinants of the sythesis of the gut microbiota that thusly impacts the attributes of safe reactions in the body. (shrink)

A Bayesian mind is, at its core, a rational mind. Bayesianism is thus well-suited to predict and explain mental processes that best exemplify our ability to be rational. However, evidence from belief acquisition and change appears to show that we do not acquire and update information in a Bayesian way. Instead, the principles of belief acquisition and updating seem grounded in maintaining a psychological immune system rather than in approximating a Bayesian processor.

Saying ┌ that ψ is F ┐ when one should have said ┌ that φ is F ┐ involves making one of two different kinds of error. Either the wrong nominal term (┌ ψ ┐ instead of ┌ φ ┐) is ascribed to the right object or the right nominal term is ascribed to the wrong object. Judgments susceptible to one kind of error are immune to the other. Indexical terms such as ‘here’ and ‘now’ exhibit a corresponding pattern (...) of immunity and susceptibility to error, which suggests that they are complex demonstratives. This should also apply to ‘I’. (shrink)

We present a computational analysis of de re, de dicto, and de se belief and knowledge reports. Our analysis solves a problem first observed by Hector-Neri Castañeda, namely, that the simple rule -/- `(A knows that P) implies P' -/- apparently does not hold if P contains a quasi-indexical. We present a single rule, in the context of a knowledge-representation and reasoning system, that holds for all P, including those containing quasi-indexicals. In so doing, we explore the difference between reasoning (...) in a public communication language and in a knowledge-representation language, we demonstrate the importance of representing proper names explicitly, and we provide support for the necessity of considering sentences in the context of extended discourse (for example, written narrative) in order to fully capture certain features of their semantics. (shrink)

Existing indexing systems used to arrange philosophical works have been shown to misrepresent the discipline in ways that reflect and perpetuate exclusionary attitudes within it. In recent years, there has been a great deal of effort to challenge those attitudes and to revise them. But as the discipline moves toward greater equality and inclusivity, the way it has indexed its work has unfortunately not. To course correct, we identify in this article some of the specific changes that are needed within (...) current indexing systems and propose a new model that could embody them. We use the Diversity Reading List in Philosophy as a case study and PhilPapers as a basis for comparison. The model we propose not only represents the discipline in a more inclusive and fair way, but it is also efficient, easy to use or implement, and adaptable for a variety of contexts. (shrink)

I critically examine the assumption that the theoretical structure that varies under theoretical symmetries is redundant and should be eliminated from a metaphysical picture of the universe, following a ‘symmetry to reality’ inference. I do so by analysing the status of coordinate change symmetries taking a pragmatic approach. I argue that coordinate systems function as indexical devices, and play an important pragmatic role for representing concrete physical systems. I examine the implications of considering this pragmatic role seriously, taking what I (...) call a perspectivist stance. My conclusion is that under a perspectivist stance, all symmetries (including local gauge symmetries) potentially have a direct empirical status: they point to dynamical aspects that are invariant under changes of operationalisation, and they constitute a guide not to reality, but to nomology and kinship. (shrink)

The case of Andrew Gobea, the first child to receive experimental gene therapy for SCID, and a reflection on the associated ethical implications of gene therapy research.

Ecological communities are seldom, if ever, biological individuals. They lack causal boundaries as the populations that constitute communities are not congruent and rarely have persistent functional roles regulating the communities’ higher-level properties. Instead we should represent ecological communities indexically, by identifying ecological communities via the network of weak causal interactions between populations that unfurl from a starting set of populations. This precisification of ecological communities helps identify how community properties remain invariant, and why they have robust characteristics. This respects the (...) diversity and aggregational nature of these complex systems while still vindicating them as units worthy of investigation. (shrink)

_(MA thesis)_ Immunity to error through misidentification (IEM) describes a sort of immunity against such a situation that the thinker wrongly identifies something as other things. Philosophers consider it as being especially relevant to first-person or de se judgments. Many philosophers seem to advance IEM as an alternative to a Cartesian method of defining first-person privilege and of circumscribing the first-person perspective. However, as more and more representative instances are substantiated as being vulnerable to error through misidentification, it is thus (...) necessary to offer an account sufficient to explain IEM. Then, there are roughly two approaches in the literature: the identification-freedom approach and the metasemantic approach. The former is characterised by the claim that the presence of IEM is always explained by the absence of an identificatory-component in the thought's grounds. The latter is more heterogeneous than the former. Nevertheless, it can be roughly described by their focus on explaining the IEM of de se thoughts based on an account of how the reference of de se thoughts is fixed, rather than just on the grounds of particular de se thoughts. However, there are still some problems with the existing accounts. More specifically, some problems from the indexical thoughts put at risk Recanati's appeal, which is viewed as a representative of the metasematic approach. Nonetheless, I think these problems can be resolved competently by pointing out the fact that there are three levels of reflection in introspection. Thoughts produced by the first level of reflection (first-level thoughts, hereafter) correspond to Recanati's implicit thoughts; Third-level thoughts are Recanati's explicit thoughts (whether it is made explicit by an extra reflective act, as Recanati puts it). However, second-level thoughts, which include a sort of aboutness in their content, could explain the subject appearing in indexical statements with IEM, guaranteeing IEM of these thoughts in the meanwhile. (shrink)

The interplay between the virus, infected cells and immune responses to SARS-CoV-2 is still under debate. By extending the basic model of viral dynamics, we propose here a formal approach to describe neutralisation versus weak (or non-)neutralisation scenarios and compare them with the possible effects of antibody-dependent enhancement (ADE). The theoretical model is consistent with the data available in the literature; we show that both weakly neutralising antibodies and ADE can result in final viral clearance or disease progression, but (...) that the immunodynamics are different in each case. As a significant proportion of the world’s population is already naturally immune or vaccinated, we also discuss the implications for secondary infections after vaccination or in the presence of immune system dysfunctions. (shrink)

Biomarkers are widely used not only as prognostic or diagnostic indicators, or as surrogate markers of disease in clinical trials, but also to formulate theories of pathogenesis. We identify two problems in the use of biomarkers in mechanistic studies. The first problem arises in the case of multifactorial diseases, where different combinations of multiple causes result in patient heterogeneity. The second problem arises when a pathogenic mediator is difficult to measure. This is the case of the oxidative stress (OS) theory (...) of disease, where the causal components are reactive oxygen species (ROS) that have very short half-lives. In this case, it is usual to measure the traces left by the reaction of ROS with biological molecules, rather than the ROS themselves. Borrowing from the philosophical theories of signs, we look at the different facets of biomarkers and discuss their different value and meaning in multifactorial diseases and system medicine to inform their use in patient stratification in personalized medicine. (shrink)

The two main features of this thesis are (i) an account of contextualized (context indexed) counterfactuals, and (ii) a non-vacuist account of counterpossibles. Experience tells us that the truth of the counterfactual is contingent on what is meant by the antecedent, which in turn rests on what context is assumed to underlie its reading (intended meaning). On most conditional analyses, only the world of evaluation and the antecedent determine which worlds are relevant to determining the truth of a conditional, and (...) consequently what its truth value is. But that results in the underlying context being fixed, when evaluating distinct counterfactuals with the same antecedent on any single occasion, even when the context underlying the evaluation of each counterfactual may vary. Alternative approaches go some of the way toward resolving this inadequacy by appealing to a difference in the consequents associated with counterfactuals with the same antecedent. That is, in addition to the world of evaluation and the antecedent, the consequent contributes to the counterfactual’s evaluation. But these alternative approaches nevertheless give a single, determinate truth value to any single conditional (same antecedent and consequent), despite the possibility that this value may vary with context. My reply to these shortcomings (chapter 4) takes the form of an analysis of a language that makes appropriate explicit access to the intended context available. That is, I give an account of a contextualized counterfactual of the form ‘In context C: If it were the case that … , then it would be the case that …’. Although my proposal is largely based on Lewis’ (1973, 1981) analyses of counterfactuals (the logic VW and its ordering semantics), it does not require that any particular logic of counterfactuals should serve as its basis – rather, it is a general prescription for contextualizing a conditional language. The advantage of working with ordering semantics stems from existing results (which I apply and develop) concerning the properties of ordering frames that facilitate fashioning and implementing a notion of contextual information preservation. Analyses of counterfactuals, such as Lewis’ (1973), that cash out the truth of counterfactuals in terms of the corresponding material conditional’s truth at possible worlds result in all counterpossibles being evaluated as vacuously true. This is because antecedents of counterpossibles are not true at any possible world, by definition. Such vacuist analyses have already been identified and challenged by a number of authors. I join this critical front, and drawing on existing proposals, I develop an impossible world semantics for a non-vacuist account of counterpossibles (chapter 5), by modifying the same system and semantics that serve the basis of the contextualized account offered in chapter 4, i.e. Lewis’ (1986) ordering semantics for the logic VW. I critically evaluate the advantages and disadvantages of key conditions on the ordering of worlds on the extended domain and show that there is a sense in which all of Lewis’ analysis of mere counterfactuals can be preserved, whilst offering an analysis of counterpossibles that meets our intuitions. The first part of chapter 1 consists of an outline of the usefulness of impossible worlds across philosophical analyses and logic. That outline in conjunction with a critical evaluation of Lewis’ logical arguments in favour of vacuism in chapter 2, and his marvellous mountain argument against impossible worlds in chapter 3, serves to motivate and justify the impossible world semantics for counterpossibles proposed in chapter 5. The second part of chapter 1 discusses the limitations that various conditional logics face when tasked to give an adequate treatment of the influence of context. That introductory discussion in conjunction with an overview of conditional logics and their various semantics in chapter 2 – which includes an in-depth exposition of Stalnaker-Lewis similarity semantics for counterfactuals – serves as the motivation and conceptual basis for the contextualized account of counterfactuals proposed in chapter 4. (shrink)

Resident microbiota do not just shape host immunity, they can also contribute to host protection against pathogens and infectious diseases. Previous reviews of the protective roles of the microbiota have focused exclusively on colonization resistance localized within a microenvironment. This review shows that the protection against pathogens also involves the mitigation of pathogenic impact without eliminating the pathogens (i.e., “disease tolerance”) and the containment of microorganisms to prevent pathogenic spread. Protective microorganisms can have an impact beyond their niche, interfering with (...) the entry, establishment, growth, and spread of pathogenic microorganisms. More fundamentally, we propose a series of conceptual clarifications in support of the idea of a “co-immunity,” where an organism is protected by both its own immune system and components of its microbiota. -/- . (shrink)

Centred on 'Foams', the third volume of his Spheres trilogy, this article questions the privilege granted by Peter Sloterdijk to motifs of inclusion and exclusion, contending that whilst his prioritization of dwelling as a central aspect of human existence provides a promising counterpoint to the dislocative and isolative effects of post-industrial capitalism, it is compromised by its dependence upon an anti-cosmopolitan outlook that views cultural distantiation as a natural and preferable state of human affairs, and valorizes a purported ontological security (...) attained through defensive postures with respect to perceived foreigners or externalities. Sloterdijk’s conceptualization of culture as a kind of immune system, it is argued, although posited as a rebuke to models of essentialism and ethno-nationalism, provides ontological support to the xenophobic critiques of immigration that are today finding increasing currency. (shrink)

Male genital problems and injuries may occur quite simply because of the scrotum and penis are not protected like other organs. Genital problems and injuries normally happen through: recreational activities (like Football, Hooky, biking, basketball), work- related tasks (like contact to irritating chemicals), downhill drop, and sexual activity. A genital injury frequently causes harsh pain that typically disappear fast without causing enduring harm. Home handling is generally all that is required for trivial problems or injuries. Pain, inflammation, staining, or (...) rashes that are coexist with other symptoms might be a source for concern. Genital problems in men is one of the most common problems which requires fast intervention. In this paper we present an expert system that help men diagnose their genital problems and give them the proper treatment. SL5 Object expert system language was used to design and implement this expert system. (shrink)

Precision medicine and molecular systems medicine (MSM) are highly utilized and successful approaches to improve understanding, diagnosis, and treatment of many diseases from bench-to-bedside. Especially in the COVID-19 pandemic, molecular techniques and biotechnological innovation have proven to be of utmost importance for rapid developments in disease diagnostics and treatment, including DNA and RNA sequencing technology, treatment with drugs and natural products and vaccine development. The COVID-19 crisis, however, has also demonstrated the need for systemic thinking and transdisciplinarity and the (...) limits of MSM: the neglect of the bio-psycho-social systemic nature of humans and their context as the object of individual therapeutic and population-oriented interventions. COVID-19 illustrates how a medical problem requires a transdisciplinary approach in epidemiology, pathology, internal medicine, public health, environmental medicine, and socio-economic modeling. Regarding the need for conceptual integration of these different kinds of knowledge we suggest the application of general system theory (GST). This approach endorses an organism-centered view on health and disease, which according to Ludwig von Bertalanffy who was the founder of GST, we call Organismal Systems Medicine (OSM). We argue that systems science offers wider applications in the field of pathology and can contribute to an integrative systems medicine by (i) integration of evidence across functional and structural differentially scaled subsystems, (ii) conceptualization of complex multilevel systems, and (iii) suggesting mechanisms and non-linear relationships underlying the observed phenomena. We underline these points with a proposal on multi-level systems pathology including neurophysiology, endocrinology, immune system, genetics, and general metabolism. An integration of these areas is necessary to understand excess mortality rates and polypharmacological treatments. In the pandemic era this multi-level systems pathology is most important to assess potential vaccines, their effectiveness, short-, and long-time adverse effects. We further argue that these conceptual frameworks are not only valid in the COVID-19 era but also important to be integrated in a medicinal curriculum. (shrink)

Background: Arthritis is very common but is not well understood. Actually, “arthritis” is not a single disease; it is an informal way of referring to joint pain or joint disease. There are more than 100 different types of arthritis and related conditions. People of all ages, sexes and races can and do have arthritis, and it is the leading cause of disability in America. More than 50 million adults and 300,000 children have some type of arthritis. It is most common (...) among women and occurs more frequently as people get older. Common arthritis joint symptoms include swelling, pain, stiffness and decreased range of motion. Symptoms may come and go. They can be mild, moderate or severe. They may stay about the same for years, but may progress or get worse over time. Severe arthritis can result in chronic pain, inability to do daily activities and make it difficult to walk or climb stairs. Arthritis can cause permanent joint changes. These changes may be visible, such as knobby finger joints, but often the damage can only be seen on X-ray. Some types of arthritis also affect the heart, eyes, lungs, kidneys and skin as well as the joints. Objectives: The main goal of this expert system is to get the appropriate diagnosis of disease and the correct treatment and give the appropriate method of treatment through several tips that concern the disease and how to treat it and we will see it through the application on the expert system. Methods: in this paper the design of the proposed Expert System which was produced to help Orthopedist in diagnosing Arthritis disease through its symptoms such as: pain on pressure in a joint , Inflammation indicated by joint swelling, Stiffness especially in the morning , Loss of flexibility of joint, Limited, joint movement, Deformity of the joints , Weight loss and fatigue , Non-specific fever and Crepitus. The proposed expert system presents an overview about Arthritis disease is given, the cause of diseases is outlined and the treatment of disease whenever possible is given out. SL5 Object Expert System language was used for designing and implementing the proposed expert system. Results: The proposed Arthritis disease diagnosis expert system was evaluated by Orthopedics students and they were satisfied with its performance. Conclusions: The Proposed expert system is very useful for Orthopedist, patients with arthritis and newly graduated Orthopedics students. (shrink)

Systemic juvenile idiopathic arthritis is classified as an autoimmune entity and a subtype of juvenile idiopathic arthritis, although it has many features of autoinflammatory-type of diseases. This review article will elaborate on the disease’s pathogenesis and its proposed relation to autoinflammatory diseases including defective innate immunity and phagocytosis response leading excessive cytokine release. It also explains the disease’s epidemiology, clinical phenotype, diagnostic challenges, complications and current advancements in the treatment of systemic juvenile idiopathic arthritis, such as IL-1 and (...) IL-6 antagonists and their impact on the disease trajectory. Care of patients with systemic juvenile idiopathic arthritis requires a comprehensive multidisciplinary team to optimize the care and avoid complications of the disease itself such as growth impairment, macrophage activation syndrome or the complications of immunosuppressant and immunomodulatory treatments. (shrink)

Male genital problems and injuries may occur quite simply because of the scrotum and penis are not protected like other organs. Genital problems and injuries normally happen through: recreational activities (like Football, Hooky, biking, basketball), workrelated tasks (like contact to irritating chemicals), downhill drop, and sexual activity. A genital injury frequently causes harsh pain that typically disappear fast without causing enduring harm. Home handling is generally all that is required for trivial problems or injuries. Pain, inflammation, staining, or rashes (...) that are coexist with other symptoms might be a source for concern. Genital problems in men is one of the most common problems which requires fast intervention. In this paper we present an expert system that help men diagnose their genital problems and give them the proper treatment. SL5 Object expert system language was used to design and implement this expert system. (shrink)

Warts and verrucas are common skin conditions caused by the human papillomavirus (HPV) infection. They present as raised, rough, or bumpy growths on the hands, feet, or other areas subjected to friction or pressure. Plantar warts exhibit a rough surface with small black dots, while genital warts have a cauliflower-like appearance. Pain or itchiness may accompany these lesions. Factors such as close contact with infected individuals and immune compromise can impact the severity and spread of warts. Diagnosis is primarily (...) based on clinical examination, and referral to a dermatologist may be necessary for uncertain cases. Treatment options range from over-the-counter remedies to professional interventions. Persistent or symptomatic lesions should be evaluated by a healthcare professional. Improved understanding and effective management of warts and verrucas are essential for optimal patient outcomes. (shrink)

How seriously should we take the idea that the mind employs mental files? Goodman and Gray (2022) argue that mental filing – a thinker rationally treating her cognitive states as being about the same thing – can be explained without files. Instead, they argue that the standard commitments of mental file theory, as represented by Recanati’s indexical model, are better seen in terms of a relational representational feature of object representations, which in turn is based on the epistemic links a (...) thinker bears to objects. This paper argues that this revision is misguided. Neither the representational property nor any basic role for epistemic links are needed for an adequate explanatory theory that makes use of the image of a mental filing system. A better alternative to the indexical model does posit files, albeit as causal-functional entities. This makes additional representational features redundant, and shows that epistemic links play a secondary role. (shrink)

The aim of this paper is to explore and understand the Albanian Party System. The analysis will cover the period from the collapse of the communist regime in 1991 until 2014. It will try to investigate what forces drive the battle of the parties, what cleavages 'divide' society and consequently the party system as well as which are the parties that count the most. in order to assess this, the paper will focus on the parliamentary parties and will relay on (...) various theoretical concepts of the contemporary literature on political parties. First it will draw on Sartori's concept of 'relevance' in order to understand whether all the parliamentary parties over the course of twenty four years of pluralism are important or not and what weight do they have. Then it will use the Laakso - Taagepera index of the Effective Number of Parties to understand how power is distributed within the parliament. (shrink)

It has been widely acknowledged that indexical thought poses a problem for traditional theories of mental content. However, recent work in philosophy has defied this received view and challenged its defenders not to rely on intuitions but rather to clearly articulate what the problem is supposed to be. For example, in “The Inessential Indexical”, Cappelen and Dever claim that there are no philosophically interesting or important roles played by essential indexical representations. This paper assesses the role of essential indexicality in (...) understanding the content of perception and argues that, if the perceptual experiences of different subjects can have the same phenomenology, and thus share a representational content (phenomenal content)—assumptions shared by a well-established research project, including a wide variety of theories—, then phenomenal content exhibit a particular kind of essential indexicality (perspectival). I also discuss how the argument is immune to Cappelen and Dever’s objections to the idea that the content of perceptual experiences is essentially indexical. (shrink)

In today’s neoliberal audit cultures university rankings, quantitative evaluation of publications by JIF or researchers by h-index are believed to be indispensable instruments for “quality assurance” in the sciences. Yet there is increasing resistance against “impactitis” and “evaluitis”. Usually overseen: Trivial errors in Thomson Reuters’ citation indexes produce severe non-trivial effects: Their victims are authors, institutions, journals with names beyond the ASCII-code and scholars of humanities and social sciences. Analysing the “Joshua Lederberg Papers” I want to illuminate eventually successful (...) ‘invention’ of science citation indexing is a product of contingent factors. To overcome severe resistance Eugene Garfield, the “father” of citation indexing, had to foster overoptimistic attitudes and to downplay the severe problems connected to global and multidisciplinary citation indexing. The difficulties to handle different formats of references and footnotes, non-Anglo-American names, and of publications in non-English languages were known to the pioneers of citation indexing. Nowadays the huge for-profit North-American media corporation Thomson Reuters is the owner of the citation databases founded by Garfield. Thomson Reuters’ influence on funding decisions, individual careers, departments, universities, disciplines and countries is immense and ambivalent. Huge technological systems show a heavy inertness. This insight of technology studies is applicable to the large citation indexes by Thomson Reuters, too. (shrink)

Information Theory, Evolution and The Origin ofLife: The Origin and Evolution of Life as a Digital Message: How Life Resembles a Computer, Second Edition. Hu- bert P. Yockey, 2005, Cambridge University Press, Cambridge: 400 pages, index; hardcover, US $60.00; ISBN: 0-521-80293-8. The reason that there are principles of biology that cannot be derived from the laws of physics and chemistry lies simply in the fact that the genetic information content of the genome for constructing even the simplest organisms is (...) much larger than the information content of these laws. Yockey in his previous book (1992, 335) In this new book, Information Theory, Evolution and The Origin ofLife, Hubert Yockey points out that the digital, segregated, and linear character of the genetic information system has a fundamental significance. If inheritance would blend and not segregate, Darwinian evolution would not occur. If inheritance would be analog, instead of digital, evolution would be also impossible, because it would be impossible to remove the effect of noise. In this way, life is guided by information, and so information is a central concept in molecular biology. The author presents a picture of how the main concepts of the genetic code were developed. He was able to show that despite Francis Crick's belief that the Central Dogma is only a hypothesis, the Central Dogma of Francis Crick is a mathematical consequence of the redundant nature of the genetic code. The redundancy arises from the fact that the DNA and mRNA alphabet is formed by triplets of 4 nucleotides, and so the number of letters (triplets) is 64, whereas the proteome alphabet has only 20 letters (20 amino acids), and so the translation from the larger alphabet to the smaller one is necessarily redundant. Except for Tryptohan and Methionine, all amino acids are coded by more than one triplet, therefore, it is undecidable which source code letter was actually sent from mRNA. This proof has a corollary telling that there are no such mathematical constraints for protein-protein communication. With this clarification, Yockey contributes to diminishing the widespread confusion related to such a central concept like the Central Dogma. Thus the Central Dogma prohibits the origin of life "proteins first." Proteins can not be generated by "self-organization." Understanding this property of the Central Dogma will have a serious impact on research on the origin of life. (shrink)

Holobionts are symbiotic assemblages composed by a macrobe host plus its symbiotic microbiota. In recent years, the ontological status of holobionts has created a great amount of controversy among philosophers and biologists: are holobionts biological individuals or are they rather ecological communities of independent individuals that interact together? Chiu and Eberl have recently developed an eco-immunity account of the holobiont wherein holobionts are neither biological individuals nor ecological communities, but hybrids between a host and its microbiota. According to their account, (...) the microbiota is not a proper part of the holobiont. Yet, it should be regarded as a set of scaffolds that support the individuality of the host. In this paper, we approach Chiu and Eberl’s account from a metaphysical perspective and argue that, contrary to what the authors claim, the eco-immunity account entails that the microorganisms that compose the host’s microbiota are proper parts of the holobiont. Second, we argue that by claiming that holobionts are hybrids, and therefore, not biological individuals, the authors seem to be assuming a controversial position about the ontology of hybrids, which are conventionally characterized as a type of biological individual. In doing so, our paper aligns with the contemporary tendency to incorporate metaphysical resources to shed light on current biological debates and builds on that to provide additional support to the consideration of holobionts as biological individuals from an eco-immunity perspective. (shrink)

This perspective paper analyzes the rising threat of retracted scientific works and the challenges of preventing the continued spreading and use of the retracted science; further, a framework is proposed for research and actions to effectively manage retractions in the information ecosystem. The precipitous increase in retractions of scientific publications is real and the complexity of retracting publications challenges current IR systems and people's information behaviors. Retracting published, especially peer-reviewed, papers in prestigious venues is a complex phenomenon involving various entities (...) through often time-consuming processes. These publications may be accessible from the original venues, digital archives, or free-access databases, but these systems differ in retrievability and output. Many systems do not identify the retractions or reasons for retractions; most systems do not treat the retracted paper and its related notices (retraction or correction) as an integrated entity. Studies found that many retracted publications continue to be cited post-retraction as valid science. A new threat is the widely spread of retracted publications on social media. Retracting invalid scientific publications has serious implications in the real world. Based on current findings, we propose (1) a framework for further research; (2) a DOI resolution to integrate the documents related to retraction/correction; (3) a structured facet taxonomy for representing and indexing the retracted, corrected, or republished publications in databases; (4) a retraction registry or database with personalized AI helper for researchers to tract retracted publications; (5) an approach for understanding how retracted publications are circulated on social media. (shrink)

Some, if not all statements containing the word 'I' seem to be 'immune to error through misidentification relative to the first-person pronoun' (Shoemaker). This immunity, however, is due to the fact that the pronoun 'I' plays no identifying role in the first place. Since no identification takes place here, the alleged immunity to misidentification should come as no surprise. But there is a second immunity thesis, which captures the peculiarity of 'I' better: The first-person pronoun is immune to (...) reference-failure. Some philosophers claim that this kind of immunity applies to the indexicals 'here' and 'now' as well. Which epistemic significance does such guaranteed reference have? Does it constitute infallible knowledge? No, the alleged immunity calls for a deflationary interpretation. It has grammatical reasons, in the Wittgensteinian sense. Therefore, the epistemic notions 'infallible knowledge' and 'immunity to error' are misleading here. (shrink)

The indexical sentence “I am here now” can be used any time and anywhere by anyone to say something true. Rather than yielding a special kind of infallible knowledge, this fact indicates that every speaker or thinker has a zero of an egocentric coordinate system at his disposal. Many idealist philosophers assume that this egocentric zero can be further reduced. The ability to make a de se-reference with the first person pronoun, they claim, need not involve spatiotemporal self-localization. The paper (...) challenges this idealistic view. Starting from the observation that even Descartes’ cogito argument, which expresses a tensed truth, involves a dated mental episode, it is argued that nothing can exist in time without being in space. The paper concludes that the egocentric zero of orientation with its three mutually dependent elements (I, here, now) cannot be further minimized. Thinkers of I-thoughts must have a spatiotemporal position. They must be Strawsonian persons rather than Cartesian egos. (shrink)

This paper will present two contributions to teaching introductory logic. The first contribution is an alternative tree proof method that differs from the traditional one-sided tree method. The second contribution combines this tree system with an index system to produce a user-friendly tree method for sentential modal logic.

The aim of this paper is to provide a theoretical framework to understand how multicellular systems realize functionally integrated physiological entities by organizing their intercellular space. From a perspective centered on physiology and integration, biological systems are often characterized as organized in such a way that they realize metabolic self-production and self-maintenance. The existence and activity of their components rely on the network they realize and on the continuous management of the exchange of matter and energy with their environment. One (...) of the virtues of the organismic approach focused on organization is that it can provide an understanding of how biological systems are functionally integrated into coherent wholes. Organismic frameworks have been primarily developed by focusing on unicellular life. Multicellularity, however, presents additional challenges to our understanding of biological systems, related to how cells are capable to live together in higher-order entities, in such a way that some of their features and behaviors are constrained and controlled by the system they realize. Whereas most accounts of multicellularity focus on cell differentiation and increase in size as the main elements to understand biological systems at this level of organization, we argue that these factors are insufficient to provide an understanding of how cells are physically and functionally integrated in a coherent system. In this paper, we provide a new theoretical framework to understand multicellularity, capable to overcome these issues. Our thesis is that one of the fundamental theoretical principles to understand multicellularity, which is missing or underdeveloped in current accounts, is the functional organization of the intercellular space. In our view, the capability to be organized in space plays a central role in this context, as it enables (and allows to exploit all the implications of) cell differentiation and increase in size, and even specialized functions such as immunity. We argue that the extracellular matrix plays a crucial active role in this respect, as an evolutionary ancient and specific (non-cellular) control subsystem that contributes as a key actor to the functional specification of the multicellular space and to modulate cell fate and behavior. We also analyze how multicellular systems exert control upon internal movement and communication. Finally, we show how the organization of space is involved in some of the failures of multicellular organization, such as aging and cancer. (shrink)

Background: Health care practitioners are recognized to have a large influence in shaping uptake of vaccine in new borns, children, adolescents, as well as adults. Parents remain more secure in their decisions when health care practitioners communicate successfully with them about vaccine dangers and benefits, the value as well as necessity for vaccinations, as well as vaccine safety. Thus, immunization remain the foundation of the primary health care system, an indisputable human right as well as a global health and development (...) success story, saving millions of lives yearly. Recently, we have vaccines to prevent more than 20 life threatening diseases, helping people of all ages live longer, healthier lives. Yet despite tremendous progress, far too many people around the world, including nearly 20 million infants yearly have insufficient access to vaccines. In some countries, progress has stalled or even reversed, and there is a real risk that complacency will undermine past achievements. Purpose: The current study aimed to explores vaccine hesitancy, its barriers and impact studies regarding COVID-19 decision impacts. Also, to provides policy and decision makers and operational staff with evidence to inform decisions to promote vaccine uptake across Bayelsa State. Methods: A literature review tried to do a deep dive by using a variety of search engines such as Scopus, Research Gate, Mendeley, Summon, PubMed, Google Scholar, Hinari, Dimension, Academia, CAB Abstract, OARE Abstract, SSRN search strategy to retrieve research publications, “grey literature” and expert working group reports, including author’s field experience. Findings: Absence of uniform methods of organization in the various health care facilities upon which we were obliged to rely. Thus affecting the overall immunization programme and health system. Hence policy must urgently address these challenges with emphasis on policy clarity while continuously improving infrastructure. Conclusions: Bayelsa State is categorized as low/poor performing as the findings suggest that the involvement of community-based leaders can improve community participation and acceptance while enhancing and strengthening integrated disease surveillance and Adverse Events Following Immunization (AEFI) monitoring and reporting systems; and conducting integrated advocacy and communications activities to promote demand for vaccination as part of increasing overall demand and acceptability of all essential Primary Health Centers (PHC) services, thus, breaking barriers of vaccine hesitancy. (shrink)

Free Will & The Tragic Predicament : Making Sense of Williams -/- The discussion in this paper aims to make better sense of free will and moral responsibility by way of making sense of Bernard Williams’ significant and substantial contribution to this subject. Williams’ fundamental objective is to vindicate moral responsibility by way of freeing it from the distortions and misrepresentations imposed on it by “the morality system”. What Williams rejects, in particular, are the efforts of “morality” to further “deepen” (...) or “refine” the notion of the voluntary, with a view to securing “ultimate justice”. It is these aims and aspirations, he argues, that take us to the precipice of scepticism. In Shame and Necessity (1993) Williams advances a vindicatory genealogy that unmasks the “illusions” and “fantasies” of our current ethical ideas as they relate to agency and responsibility. What we are then left with is the task of “recasting our ethical conceptions” . It is here that Williams is especially insistent on the importance and value of historical consciousness and reflection. The role of our reflections about the Greeks and tragedy is precisely to show that in order to move forward, into the future, we need to first look back at where we have come from. The value of these “untimely” observations is that they provide us with alternatives and options that we might otherwise lack. What we discover, when we consider the Greeks, is their commitment to a “pessimism of strength” that rests on rejecting scepticism. It is this two-sided perspective on our ethical predicament that delivers a more truthful account of our human situation, one that will help us discard those illusions and fantasies of "morality" that we are “better off” without. An account of this kind refuses to accept an optimism that insists that any form of responsible ethical life must be one that is immune to the influence of luck and fate. This is the fundamental lesson that we can learn from the ancient Greeks and that Williams seeks to “recover” for us. (shrink)

In bioethics vaccine refusal is often discussed as an instance of free riding on the herd immunity of an infectious disease. However, the social science of vaccine refusal suggests that the reasoning behind refusal to vaccinate more often stems from previous negative experiences in healthcare practice as well as deeply felt distrust of healthcare institutions. Moreover, vaccine refusal often acts like an exit mechanism. Whilst free riding is often met with sanctions, exit, according to Albert Hirschman’s theory of exit and (...) voice is most efficiently met by addressing concerns and increasing the quality and number of feedback channels. If the legitimate grievances responsible for vaccine refusal are not heard or addressed by healthcare policy, further polarization of attitudes to vaccines is likely to ensue. Thus, there is a need in the bioethics of vaccine refusal to understand the diverse ethical questions of this inflammable issue in addition to those of individual responsibility to vaccinate. (shrink)

This study presents a description of an open database on scientific output of Vietnamese researchers in social sciences and humanities, one that corrects for the shortcomings in current research publication databases such as data duplication, slow update, and a substantial cost of doing science. Here, using scientists’ self-reports, open online sources and cross-checking with Scopus database, we introduce a manual system and its semi-automated version of the database on the profiles of 657 Vietnamese researchers in social sciences and humanities who (...) have published in Scopus-indexed journals from 2008 to 2018. The final system also records 973 foreign co-authors, 1,289 papers, and 789 affiliations. The data collection method, highly applicable for other sources, could be replicated in other developing countries while its content be used in cross-section, multivariate, and network data analyses. The open database is expected to help Vietnam revamp its research capacity and meet the public demand for greater transparency in science management. (shrink)

The article aims to define the management mechanism of complex, open dynamic systems with human participation. The following parts of the system life-cycle were identified and unified in the theoretical scope: general and specific compositional elements of repeating changes, marginal index boundaries, the dynamics of the compositional elements of the lifecycle, the key points of the change in the character of the index dynamics. In the practical scope, two common trends of socio-economical system life-cycle management are considered. The (...) first trend is the regulation of the comprising element ratio, which provides the increase in the duration of the maximally effective performance of a functioning system. The second trend is the regulation of the reproduction time of a new system. The systems life cycle aspects are investigated in almost all sciences and studied within many disciplines in the field of higher education. Therefore, deepening the mastery of scientific and methodological foundations of the life cycle of a complex open dynamic system is useful for any subject in everyday and practical activities. A human being – in the formation of own human capital. Families – when it is formed, the birth of children, the distribution of income and expenses. Companies – for efficient business activities. As well as local communities, local self-government bodies, public authorities and global entities within their profile activities. The results of the research provide the possibility of the development of applicable mechanisms for effectiveness and stability enhancement of managerial and entrepreneurial operation in business projects. (shrink)

The stronger the level of economic integration between countries, the greater the need to study the formation patterns of the stock market reaction to the financial information signals. This concerns the Ukrainian stock market, which is now in its infancy, and which reaction to financial information signals is sometimes ambiguous. The research aims to identify the formation patterns of return and volatility indicators of the Ukrainian stock market reaction to the US financial information signals. To assess the direct nature of (...) US financial information signals effect on the PFTS stock index, the GARCH econometric modeling toolkit was applied. The research information base is the PFTS stock index and the Federal Reserve System financial information signals at the discount rate for 2000–2019. The fetch is divided into intervals corresponded to the ascent and decline phases of the financial cycle. It was found that an unforeseen increase in the discount rate at the financial cycle decline phase by 25 basis points decreases the PFTS stock index return, on average by 2.9%. Besides, the hypothesis about the general change stabilizing effect in the discount rate on the Ukrainian stock market volatility at the financial cycle growth phase was confirmed. Nevertheless, for investors, the most essential is the regulator’s monetary signals in the discount rate at the financial cycle decline phases rather than at the ascent phases because there is a more significant increase in the volatility level. (shrink)

While in many countries the use of unmanned systems is still in its infancy, other countries, most notably the US and Israel, are much ahead. Most of the systems in operation today are unarmed and are mainly used for reconnaissance and clearing improvised explosive devices. But over the last years the deployment of armed military robots is also on the increase, especially in the air. This might make unethical behavior less likely to happen, seeing that unmanned systems are immune (...) to what are considered to be main causes of misconduct on the battlefield: frustration, boredom, and anger. The use of robots raises some ethical questions, though, and this paper attempts to give an overview of issues at stake, such as the role of emotions, civilian casualties, just war theory, and responsibility. (shrink)

In this paper, I argue that what counts as the proper function of a trait is a matter of the de facto perspective that the biological system, itself, possesses on what counts as proper functioning for that trait. Unlike non-perspectival accounts, internal perspectivalism does not succumb to generality problems. But unlike external perspectivalism, internal perspectivalism can provide a fully naturalistic, mind-independent grounding of proper function and natural norms. The attribution of perspectives to biological systems is intended to be neither metaphorical (...) nor anthropomorphic: I do not mean to imply that such systems thereby must possess agency, cognition, intentions, concepts, or mental or psychological states. Instead, such systems provide the grounding for norms of performance when they internally enforce their own standard of (i.e., their own perspective on) what constitutes proper functioning or malfunctioning. By operating with a fixed, determinate level of generality, such systems provide the basis for an account of proper function that is immune to generality problems. (shrink)

We aim to do two things in this article. On the positive end, our goal is to explain how some seemingly incompatible aspects of belief live together, by presenting distinct mechanistic explanations of each of them: in particular we want to show how belief can be discerning, credulous, rational, and irrational. After clarifying our positive view, we take aim at some competitor views in the second half of the paper, particularly offering critiques of epistemic vigilance and social marketplace accounts of (...) belief. We conclude by inviting proponents to provide an architecture for belief that can be tested against existing models. (shrink)

De se attitudes seem to play a special role in action and cognition. This raises a challenge to the traditional way in which mental attitudes have been understood. In this chapter, we review the case for thinking that de se attitudes require special theoretical treatment and discuss various ways in which the traditional theory can be modified to accommodate de se attitudes.

Somatic diversification of antigen receptor genes depends on the activity of enzymes whose homologs participate in a mutagenic DNA repair in unicellular species. Indeed, by engaging error-prone polymerases, gap filling molecules and altered mismatch repair pathways, lymphocytes utilize conserved components of genomic stress response systems, which can already be found in bacteria and archaea. These ancient systems of mutagenesis and repair act to increase phenotypic diversity of microbial cell populations and operate to enhance their ability to produce fit variants during (...) stress. Coopted by lymphocytes, the ancient mutagenic processing systems retained their diversification functions instilling the adaptive immune cells with enhanced evolvability and defensive capacity to resist infection and damage. As reviewed here, the ubiquity and conserved character of specialized variation-generating mechanisms from bacteria to lymphocytes highlight the importance of these mechanisms for evolution of life in general. (shrink)

Background: Adequate immunity to COVID-19 apparently cannot be attained in Germany by voluntary vaccination alone, and therefore the introduction of mandatory COVID-19 vaccination is still under consideration. We present findings on the potential acceptance of such a requirement by the German population, and we report on the reasons given for accepting or rejecting it and how these reasons vary according to population subgroup. -/- Methods: We used representative data from the Socio-Economic Panel for the period January to December 2021. We (...) linked the respondents’ answers concerning mandatory COVID-19 vaccination to information about their sociodemographic characteristics, state of health, political attitudes, and degree of confidence in the judicial and political systems. We analyzed these data using univariate, bivariate, and multivariate statistical methods. -/- Results: Just over half of the respondents (50.44% [49.08%; 51.79%]) favored mandatory COVID-19 vaccination. Among the supporters, the reason most frequently given (95.22% [94.45; 96.00]) was that, without such a requirement, not enough people would be vaccinated. Among the opponents of mandatory COVID-19 vaccination (49.56% [48.21%; 50.92%]), by far the most common reason given for opposing it was a desire to uphold individual freedom (91.36% [90.31%; 92.40%]). Persons supporting mandatory COVID-19 vaccination, on average, older than those who opposed it; they less commonly had an education beyond secondary school, were less healthy, tended to have no children, had centrist political views, and expressed more confidence in the political system. The largest difference between the two groups was that about 90% of supporters of mandatory COVID-19 vaccination were themselves vaccinated, compared to only about 62% of opponents. -/- Conclusion: The lack of consensus on this issue among politicians and physicians in Germany is reflected in a similar lack of consensus in the German population as a whole. A discussion of the appropriate understanding of individual freedom would be the most promising way to widen the acceptance of mandatory COVID-19 vaccination. A commonly expressed conception of freedom that permits the deliberate endangerment of other people’s health seems morally questionable. -/- DOI: 10.3238/arztebl.m2022.0174. (shrink)

Artificial intelligence (AI) is increasingly expected to disrupt the ordinary functioning of society. From how we fight wars or govern society, to how we work and play, and from how we create to how we teach and learn, there is almost no field of human activity which is believed to be entirely immune from the impact of this emerging technology. This poses a multifaceted problem when it comes to designing and understanding regulatory responses to AI. This article aims to: (...) (i) defend the need for a novel conceptual model for understanding the systemic legal disruption caused by new technologies such as AI; (ii) to situate this model in relation to preceding debates about the interaction of regulation with new technologies (particularly the ‘cyberlaw’ and ‘robolaw’ debates); and (iii) to set out a detailed model for understanding the legal disruption precipitated by AI, examining both pathways stemming from new affordances that can give rise to a regulatory ‘disruptive moment’, as well as the Legal Development, Displacement or Destruction that can ensue. The article proposes that this model of legal disruption can be broadly generalisable to understanding the legal effects and challenges of other emerging technologies. (shrink)

K. R. Popper distinguished between two main uses of logic, the demonstrational one, in mathematical proofs, and the derivational one, in the empirical sciences. These two uses are governed by the following methodological constraints: in mathematical proofs one ought to use minimal logical means (logical minimalism), while in the empirical sciences one ought to use the strongest available logic (logical maximalism). In this paper I discuss whether Popper’s critical rationalism is compatible with a revision of logic in the empirical sciences, (...) given the condition of logical maximalism. Apparently, if one ought to use the strongest logic in the empirical sciences, logic would remain immune to criticism and, thus, non-revisable. I will show that critical rationalism is theoretically compatible with a revision of logic in the empirical sciences. However, a question that remains to be clarified by the critical rationalists is what kind of evidence would lead them to revise the system of logic that underlies a physical theory, such as quantum mechanics? Popper’s falsificationist methodology will be compared with the recently advocated extension of the abductive methodology from the empirical sciences to logic by T. Williamson, since both of them arrive at the same conclusion concerning the status of classical logic. (shrink)

Bernard Williams articulated his later political philosophy notably in response to Ronald Dworkin, who, striving for coherence or integrity among our political concepts, sought to immunize the concepts of liberty and equality against conflict. Williams, doubtful that we either could or should eliminate the conflict, resisted the pursuit of conceptual integrity. Here, I reconstruct this Dworkin–Williams debate with an eye to drawing out ideas of ongoing philosophical and political importance. The debate not only exemplifies Williams's political realism and its connection (...) to his critique of the morality system. It also illustrates the virtues and hazards of contemporary efforts to ameliorate or engineer our concepts; it indicates what political philosophy might look to in appraising political concepts; it adverts to the different needs these concepts have to meet if they are to sustain a politics of pluralism, deal with polarization, and secure the consent of those who end up on the losing side of political decisions; and it presents us with two starkly contrasting conceptions of politics itself, of the place of political values within it, and of our prospects of reducing the uncomfortably conflictual character of those values through philosophy. (shrink)

List of Illustrations Introduction 1 The Didactic and the Elegant: Some Thoughts on Scientific and Technological Illustrations in the Middle Ages and Renaissance 3 2 Temples of the Body and Temples of the Cosmos: Vision and Visualization in the Vesalian and Copernican Revolutions 40 3 Descartes’s Scientific Illustrations and ’la grande mecanique de la nature’ 86 4 Illustrating Chemistry 135 5 Representations of the Natural System in the Nineteenth Century 164 6 Visual Representation in Archaeology: Depicting the Missing-Link in Human (...) Origins 184 7 Towards an Epistemology of Scientific Illustration 215 8 Illustration and Inference 250 9 Visual Models and Scientific Judgment 269 10 Are Pictures Really Necessary? The Case of Sewall Wright’s ’Adaptive Landscapes’ 303 Bibliography 339 Notes on Contributors 373 Index 377. (shrink)