BACKGROUND Patients with chronic pain face significant barriers in finding clinicians to manage long-term opioid therapy (LTOT). For patients on LTOT, it is increasingly common to have them sign opioid treatment agreements (OTAs). OTAs enumerate the risks of opioids, as informed consent documents would, but also the requirements that patients must meet to receive LTOT. While there has been an ongoing scholarly discussion about the practical and ethical implications of OTA use in the abstract, little is known about how clinicians (...) use them and if OTAs themselves modify clinician prescribing practices. OBJECTIVE To determine how clinicians use OTAs and the potential impacts of OTAs on opioid prescribing. DESIGN We conducted qualitative analysis of four focus groups of clinicians from a large Midwestern academic medical center. Groups were organized according to self-identified prescribing patterns: two groups for clinicians who identified as prescribers of LTOT, and two who did not. PARTICIPANTS 17 clinicians from General Internal Medicine, Family Medicine, and Palliative Care were recruited using purposive, convenience sampling. APPROACH Discussions were recorded, transcribed, and analyzed for themes using reflexive thematic analysis by a multidisciplinary team. KEY RESULTS Our analysis identified three main themes: (1) OTAs did not influence clinicians’ decisions whether to use LTOT generally but did shape clinical decision-making for individual patients; (2) clinicians feel OTAs intensify the power they have over patients, though this was not uniformly judged as harmful; (3) there is a potential misalignment between the intended purposes of OTAs and their implementation. CONCLUSION This study reveals a complicated relationship between OTAs and access to pain management. While OTAs seem not to impact the clinicians’ decisions about whether to use LTOT generally, they do sometimes influence prescribing decisions for individual patients. Clinicians shared complex views about OTAs’ purposes, which shows the need for more clarity about how OTAs could be used to promote shared decision-making, joint accountability, informed consent, and patient education. (shrink)

We argue that the universal recommendations against “off-label” pediatric use of approved COVID-19 issued by the FDA, CDC, and AAP are overbroad. Especially for higher-risk children, vaccination can be ethically justified even before FDA authorization or approval – and similar reasoning is relevant for even younger patients. Legal risks can also be managed, although the FDA, CDC, and Department of Health and Human Services (HHS) should move quickly to provide clarity.

Anydomainofscientificresearchhasitssustainingorthodoxy. Thatis, research on a problem, whether in astronomy, physics, or biology, is con- ducted against a backdrop of broadly shared assumptions. It is these as- sumptionsthatguideinquiryandprovidethecanonofwhatisreasonable-- of what "makes sense." And it is these shared assumptions that constitute a framework for the interpretation of research results. Research on the problem of how we see is likewise sustained by broadly shared assump- tions, where the current orthodoxy embraces the very general idea that the business of the visual system is to (...) create a detailed replica of the visual world, and that it accomplishes its business via hierarchical organization and by operatingessentiallyindependently of other sensorymodalitiesas well as independently of previous learning, goals, motor planning, and motor execution. (shrink)

Theorists in various scientific disciplines offer radically different accounts of the origin of violent behavior in humans, but it is not clear how the study of violence is to be scientifically grounded. This problem is made more complicated because both what sorts of acts constitute violence and what needs to be appealed to in explaining violence differs according to social scientists, biologists, anthropologists and neurophysiologists, and this generates serious problems with respect to even attempting to ascertain the differential bona fides (...) of these various explanatory programs. As a consequence, there is little theoretical reason to suspect that efforts to prevent violence will have any appreciable effect. In this paper we investigate the general issue of whether any of the general theoretical approaches to violent behavior can reasonably be taken to be the best approach to the explanation of seriously violent behavior. Our more specific aim is to examine the controversial explanation of violent behavior offered by Lonnie Athens in order to ascertain whether it can be seriously considered to be the best explanation of violent behavior. (shrink)

The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to (...) existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource providing details on the people, policies, and issues being addressed in association with OBI. (shrink)

Zu den Anliegen dieses Beitrags zählt zum einen die Diskussion einiger aktuellerer Argumente gegen die Vereinbarkeit eines Dualismus von Eigenschaften mit einem (Substanz-)Physikalismus und zum anderen in einer Präsentation und Verteidigung des von E. J. Lowe (1950-2014) vertretenen (Nicht-Cartesianischen) Substanzendualismus. -/- Erschienen in: Patricia Wallusch/ Heinrich Watzka (Hrsg.): Verkörpert existieren. Ein Beitrag zur Metaphysik menschlicher Personen, Münster: Aschendorff 2015, pp. 59-70. ISBN 978-3-402-11892-4 .

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)

VAN PRAAG (Paul), Introduction : le Père Henri Bosmans, histo­rien des mathématiques (pp. 7-16). SAUVAGE (Pierre), Notice biographique du Père Henri Bosmans (pp. 17-25). HERMANS (Michel), Henri Bosmans : sa formation et ses réseaux de rela­tions (pp. 27-72). DELANGHE (Richard), Quelques aspects de la vie et de l’œuvre de Paul Mansion (1844-1919) (pp. 73-82). BRIGAGLIA (Aldo), Saccheri vu par Corrado Segre en Italie et par Mansion et Bosmans en Belgique / traduit de l’italien par Bruna GAINO et Patricia RADELET-DE (...) GRAVE (pp. 83-104). MAWHIN (Jean), La tentative belge d’édition des œuvres complètes d’Euler vue par Henri Bos­mans (pp. 105-133). GOLVERS (Noël), Henri Bosmans, s.j., et la mission jésuite en Chine / traduit du néerlandais par Anne-Sophie MEURICE (pp. 135-152). ROMANO (Antonella), Henri Bosmans, jésuite et historien des mathéma­tiques dans la Belgique du premier XXe siècle (pp. 153-168). SAUVAGE (Pierre), Le Père Henri Bosmans et l’historiographie au tournant du XXe siècle (pp. 169-187). RADELET-DE GRAVE (Patricia), Le fonds Henri Bos­mans / avec un ajout de Michel HERMANS (pp. 189-215). MANSION (Paul), Correspondance de Paul Mansion adres­sée à Henri Bosmans / introduction, trans­cription et annotation par Michel HERMANS (pp. 217-251). HEEFFER (Albrecht) – HERMANS (Michel) – STOFFEL (Jean-François), Bibliographie d’Henri Bosmans (pp. 253-298). (shrink)

Cartesian arguments for global skepticism about the external world start from the premise that we cannot know that we are not in a Cartesian scenario such as an evil-demon scenario, and infer that because most of our empirical beliefs are false in such a scenario, these beliefs do not constitute knowledge. Veridicalist responses to global skepticism respond that arguments fail because in Cartesian scenarios, many or most of our empirical beliefs are true. Some veridicalist responses have been motivated using verificationism, (...) externalism, and coherentism. I argue that a more powerful veridicalist response to global skepticism can be motivated by structuralism, on which physical entities are understood as those that play a certain structural role. I develop the structuralist response and address objections. (shrink)

This special issue of HYPATIA: A Journal of Feminist Philosophy entitled "Women, Art, and Aesthetics" highlights the expanded range of topics at center stage in feminist philosophical inquiry to date (2003): recontextualizing women artists (essays by Patricia Locke, Eleanor Heartney, and Michelle Meagher), bodies and beauty (Ann J. Cahill, Sheila Lintott, Janell Hobson, Richard Shusterman, Joanna Frueh), art, ethics, politics, law (A. W. Eaton, Amy Mullin, L. Ryan Musgrave, Teresa Winterhalter), and review essays by Estella Lauter and Flo Leibowitz. (...) Annotated bibliography by Joshua Shaw. (shrink)

Philosophy of biology is often said to have emerged in the last third of the twentieth century. Prior to this time, it has been alleged that the only authors who engaged philosophically with the life sciences were either logical empiricists who sought to impose the explanatory ideals of the physical sciences onto biology, or vitalists who invoked mystical agencies in an attempt to ward off the threat of physicochemical reduction. These schools paid little attention to actual biological science, and as (...) a result philosophy of biology languished in a state of futility for much of the twentieth century. The situation, we are told, only began to change in the late 1960s and early 1970s, when a new generation of researchers began to focus on problems internal to biology, leading to the consolidation of the discipline. In this paper we challenge this widely accepted narrative of the history of philosophy of biology. We do so by arguing that the most important tradition within early twentieth-century philosophy of biology was neither logical empiricism nor vitalism, but the organicist movement that flourished between the First and Second World Wars. We show that the organicist corpus is thematically and methodologically continuous with the contemporary literature in order to discredit the view that early work in the philosophy of biology was unproductive, and we emphasize the desirability of integrating the historical and contemporary conversations into a single, unified discourse. (shrink)

The New Evil Demon problem has been hotly debated since the case was introduced in the early 1980’s (e.g. Lehrer and Cohen 1983; Cohen 1984), and there seems to be recent increased interest in the topic. In a forthcoming collection of papers on the New Evil Demon problem (Dutant and Dorsch, forthcoming), at least two of the papers, both by prominent epistemologists, attempt to resist the problem by appealing to the distinction between justification and excuses. My primary aim here is (...) to critically evaluate this new excuse maneuver as a response to the New Evil Demon problem. -/- Their response attempts to give us reason to reject the idea that victims of the New Evil Demon have justification for believing as they do. I shall argue that this approach is ultimately unsuccessful, however much of value can be learned from these attempts. In particular, progress in the debate can be made by following those who advance the excuse maneuver and make explicit the connection between epistemic justification and epistemic norms. By doing so, the questions being debated are clarified, as is the methodology being used to attempt to answer them. (shrink)

Online shaming is a subject of import for social philosophy in the Internet age, and not simply because shaming seems generally bad. I argue that social philosophers are well-placed to address the imaginal relationships we entertain when we engage in social media; activity in cyberspace results in more relationships than one previously had, entailing new and more responsibilities, and our relational behaviors admit of ethical assessment. I consider the stresses of social media, including the indefinite expansion of our relationships and (...) responsibilities, and the gap between the experiences of those shamed and the shamers’ appreciation of the magnitude of what they do when they shame; I connect these to the literature suggesting that some intuitions fail to guide our ethics. I conclude that we each have more power than we believe we do or than we think carefully about exerting in our online imaginal relations. Whether we are the shamers or the shamed, we are unable to control the extent to which intangible words in cyberspace take the form of imaginal relationships that burden or brighten our self-perceptions. (shrink)

Decisions are made under uncertainty when there are distinct outcomes of a given action, and one is uncertain to which the act will lead. Decisions are made under indeterminacy when there are distinct outcomes of a given action, and it is indeterminate to which the act will lead. This paper develops a theory of (synchronic and diachronic) decision-making under indeterminacy that portrays the rational response to such situations as inconstant. Rational agents have to capriciously and randomly choose how to resolve (...) the indeterminacy relevant to a given choice-situation, but such capricious choices once made constrain how they will choose in the future. The account is illustrated by the case of self-interested action in situations where it is indeterminate whether you yourself will survive to benefit or suffer the consequences. The conclusion emphasizes some distinctive anti-hedging predictions of the account. (shrink)

Memory technologies are cultural artifacts that scaffold, transform, and are interwoven with human biological memory systems. The goal of this article is to provide a systematic and integrative survey of their philosophical dimensions, including their metaphysical, epistemological and ethical dimensions, drawing together debates across the humanities, cognitive sciences, and social sciences. Metaphysical dimensions of memory technologies include their function, the nature of their informational properties, ways of classifying them, and their ontological status. Epistemological dimensions include the truth-conduciveness of external memory, (...) the conditions under which external memory counts as knowledge, and the metacognitive monitoring of external memory processes. And lastly, ethical and normative dimensions include the desirability of the effects memory technologies have on biological memory, their effects on self and culture, and their moral status. Whilst the focus in the article is largely philosophical and conceptual, empirical issues such as the way we interact with memory technologies in various contexts are also discussed. We thus take a naturalistic approach in which philosophical and empirical concepts and approaches are seen as continuous. (shrink)

This paper argues for a Husserlian account of phenomenal intentionality. Experience is intentional insofar as it presents a mind-independent, objective world. Its doing so is a matter of the way it hangs together, its having a certain structure. But in order for the intentionality in question to be properly understood as phenomenal intentionality, this structure must inhere in experience as a phenomenal feature. Husserl’s concept of horizon designates this intentionality-bestowing experiential structure, while his concept of motivation designates the unique phenomenal (...) character of this structure as it is experientially lived through. The way experience hangs together is itself a phenomenal feature of experience. (shrink)

Intellectual autonomy has long been identified as an epistemic virtue, one that has been championed influentially by Kant, Hume and Emerson. Manifesting intellectual autonomy, at least, in a virtuous way, does not require that we form our beliefs in cognitive isolation. Rather, as Roberts and Wood note, intellectually virtuous autonomy involves reliance and outsourcing to an appropriate extent, while at the same time maintaining intellectual self-direction. In this essay, I want to investigate the ramifications for intellectual autonomy of a particular (...) kind of epistemic dependence: cognitive enhancement. Cognitive enhancements involve the use of technology and medicine to improve cognitive capacities in healthy individuals, through mechanisms ranging from smart drugs to brain-computer interfaces. With reference to case studies in bioethics, as well as the philosophy of mind and cognitive science, it is shown that epistemic dependence, in this extreme form, poses a prima facie threat to the retention of intellectual autonomy, specifically, by threatening to undermine our intellectual self-direction. My aim will be to show why certain kinds of cognitive enhancements are subject to this objection from self-direction, while others are not. Once this is established, we’ll see that even some extreme kinds of cognitive enhancement might be not merely compatible with, but constitutive of, virtuous intellectual autonomy. (shrink)

Modus ponens is the argument from premises of the form If A, then B and A to the conclusion B. Nearly all participants agree that the modus ponens conclusion logically follows when the argument appears in this Basic form. However, adding a further premise can lower participants’ rate of agreement—an effect called suppression. We propose a theory of suppression that draws on contemporary ideas about conditional sentences in linguistics and philosophy. Semantically, the theory assumes that people interpret an indicative conditional (...) as a context-sensitive strict conditional: true if and only if its consequent is true in each of a contextually determined set of situations in which its antecedent is true. Pragmatically, the theory claims that context changes in response to new assertions, including new conditional premises. Thus, the conclusion of a modus ponens argument may no longer be accepted in the changed context. Psychologically, the theory describes people as capable of reasoning about broad classes of possible situations, ordered by typicality, without having to reason about individual possible worlds. The theory accounts for the main suppression phenomena, and it generates some novel predictions that new experiments confirm. (shrink)

What makes an intellectual virtue a virtue? A straightforward and influential answer to this question has been given by virtue-reliabilists: a trait is a virtue only insofar as it is truth-conducive. In this paper I shall contend that recent arguments advanced by Jack Kwong in defence of the reliabilist view are good as far as they go, in that they advance the debate by usefully clarifying ways in how best to understand the nature of open-mindedness. But I shall argue that (...) these considerations do not establish the desired conclusions that open-mindedness is truth-conducive. To establish these much stronger conclusions we would need an adequate reply to what I shall call Montmarquet’s objection. I argue that Linda Zagzebski’s reply to Montmarquet’s objection, to which Kwong defers, is inadequate. I conclude that it is contingent if open-mindedness is truth-conducive, and if a necessary tie to truth is what makes an intellectual virtue a virtue, then the status of open-mindedness as an intellectual virtue is jeopardised. We either need an adequate reliabilist response to Montmarquet’s objection, or else seek alternative accounts of what it is that makes a virtue a virtue. I conclude by briefly outlining some alternatives. (shrink)

Abstract— This study aimed to identify the degree of use of the capabilities of decision-support systems in Palestinian institutions higher education, Aqsa University in Gaza - a case study. The study used a analytical descriptive approach, and the researchers used the of questionnaire tool to collect the data, the researchers using stratified random sample distributed (150) questioners to the study population and (126) was obtained back with rate of 84%. The study showed that the most important results are: that senior (...) management supports the existence of decision support systems and that there is approval by the respondents on the paragraphs of the use of the capabilities of decision support systems in general. And that there are no significant differences between the averages of the answers of respondents differences about the degree of use of decision support systems capabilities attributed to personal data. The study also concluded a series of recommendations including: increasing the adoption of the senior management decision support in their decision-making systems. And increased regulatory attention to the potential available to decision support systems directly to the senior management in the Palestinian universities in the Gaza Strip. There is an increased interest in the physical and technical possibilities available for the use of decision support systems. There is an increased interest in human potential available for the use of decision support systems. Investment of information available to universities in building the capacities of integration techniques and other information technology capabilities. The empowerment of human resources in universities and participating in making decisions concerning the construction of the capabilities of information technology. (shrink)

While openmindedness is often cited as a paradigmatic example of an intellectual virtue, the connection between openmindedness and truth is tenuous. Several strategies for reconciling this tension are considered, and each is shown to fail; it is thus claimed that openmindedness, when intellectually virtuous, bears no interesting essential connection to truth. In the final section, the implication of this result is assessed in the wider context of debates about epistemic value.

Although they are continually compositionally reconstituted and reconfigured, organisms nonetheless persist as ontologically unified beings over time – but in virtue of what? A common answer is: in virtue of their continued possession of the capacity for morphological invariance which persists through, and in spite of, their mereological alteration. While we acknowledge that organisms‟ capacity for the “stability of form” – homeostasis - is an important aspect of their diachronic unity, we argue that this capacity is derived from, and grounded (...) in a more primitive one – namely, the homeodynamic capacity for the “specified variation of form”. In introducing a novel type of causal power – a „structural power‟ – we claim that it is the persistence of their dynamic potential to produce a specified series of structurally adaptive morphologies which grounds organisms‟ privileged status as metaphysically “one over many” over time. (shrink)

Although contemporary metaphysics has recently undergone a neo-Aristotelian revival wherein dispositions, or capacities are now commonplace in empirically grounded ontologies, being routinely utilised in theories of causality and modality, a central Aristotelian concept has yet to be given serious attention – the doctrine of hylomorphism. The reason for this is clear: while the Aristotelian ontological distinction between actuality and potentiality has proven to be a fruitful conceptual framework with which to model the operation of the natural world, the distinction between (...) form and matter has yet to similarly earn its keep. In this chapter, I offer a first step toward showing that the hylomorphic framework is up to that task. To do so, I return to the birthplace of that doctrine - the biological realm. Utilising recent advances in developmental biology, I argue that the hylomorphic framework is an empirically adequate and conceptually rich explanatory schema with which to model the nature of organisms. (shrink)

Our question is this: What makes an act one of entrapment? We make a standard distinction between legal entrapment, which is carried out by parties acting in their capacities as (or as deputies of) law- enforcement agents, and civil entrapment, which is not. We aim to provide a definition of entrapment that covers both and which, for reasons we explain, does not settle questions of permissibility and culpability. We explain, compare, and contrast two existing definitions of legal entrapment to commit (...) a crime that possess this neutrality. We point out some problems with the extensional correctness of these definitions and propose a new definition that resolves these problems. We then extend our definition to provide a more general definition of entrapment, encompassing both civil and legal cases. Our definition is, we believe, closer to being extensionally correct and will, we hope, provide a clearer basis for future discussions about the ethics of entrapment than do the definitions upon which it improves. (shrink)

You don’t know that p unless it’s on account of your cognitive abilities that you believe truly that p. Virtue epistemologists think there’s some such ability constraint on knowledge. This looks to be in considerable tension, though, with putative faith- based knowledge. For it can easily seem that when you believe something truly on the basis of faith this isn't because of anything you're competent to do. Rather faith-based beliefs are a product of divine agency. Appearances notwithstanding, I argue in (...) this paper that there’s no deep tension between faith-based knowledge and virtue epistemology. Not if we learn to conceive of faith as a kind of extended knowledge. (shrink)

What considerations place genuine constraints on an adequate semantics for normative and evaluative expressions? Linguists recognize facts about ordinary uses of such expressions and competent speakers’ judgments about which uses are appropriate. The contemporary literature reflects the widespread assumption that linguists don’t rely upon an additional source of data—competent speakers’ judgments about possible disagreement with hypothetical speech communities. We have several good reasons to think that such judgments are not probative for semantic theorizing. Therefore, we should accord these judgments no (...) probative value for the development of a semantics for our moral terms. Such judgments can no longer be presumed to put pressure on theories according to which our moral expressions share a semantics with ordinary, descriptive terms. Many rivals to pure, Descriptivist theories count among their advantages the ability to accommodate these judgments. If these judgments have no probative value, such theories lose an important source of support. (shrink)

This paper aims for a more robust epistemological disjunctivism (ED) by offering on its behalf a new and better response to the ‘new evil genius’ problem. The first section articulates the ‘new evil genius challenge’ (NEG challenge) to ED, specifying its two components: the ‘first-order’ and ‘diagnostic’ problems for ED. The first-order problem challenges proponents of ED to offer some explanation of the intuition behind the thought that your radically deceived duplicate is no less justified than you are for adopting (...) her perceptual beliefs. In the second section, I argue that 'blamelessness' explanations are inadequate to the task and offer better explanations in their place—that of ‘trait-level virtue’ and ‘reasonability’. The diagnostic problem challenges proponents of ED to explain why it is that classical internalists disagree with them about how to interpret 'new evil genius' considerations. The proponent of ED owes some error theory. I tackle this problem in the third section, arguing that classical internalists overlook disjunctivist interpretations of new evil genius intuitions owing to a mistaken commitment to a ‘vindicatory’ explanation of perceptual knowledge. (shrink)

Epistemological disjunctivism says that one can know that p on the rational basis of one’s seeing that p. The basis problem for disjunctivism says that that can’t be since seeing that p entails knowing that p on account of simply being the way in which one knows that p. In defense of their view disjunctivists have rejected the idea that seeing that p is just a way of knowing that p (the SwK thesis). That manoeuvre is familiar. In this paper (...) I explore the prospects for rejecting instead the thought that if the SwK thesis is true then seeing that p can’t be one’s rational basis for perceptual knowledge. I explore two strategies. The first situates disjunctivism within the context of a ‘knowledge-first’ approach that seeks to reverse the traditional understanding of the relationship between perceptual knowledge and justification (or rational support). But I argue that a more interesting strategy situates disjunctivism within a context that accepts a more nuanced understanding of perceptual beliefs. The proposal that I introduce reimagines disjunctivism in light of a bifurcated conception of perceptual knowledge that would see it cleaved along two dimensions. On the picture that results perceptual knowledge at the judgemental level is rationally supported by perceptual knowledge at the merely functional or ‘animal’ level. This supports a form of disjunctivism that I think is currently off the radar: one that’s consistent both with the SwK thesis and a commitment to a traditional reductive account of perceptual knowledge. (shrink)

Internalist approaches to epistemic justification are, though controversial, considered a live option in contemporary epistemology. Accordingly, if ‘active’ externalist approaches in the philosophy of mind—e.g. the extended cognition and extended mind theses—are _in principle_ incompatible with internalist approaches to justification in epistemology, then this will be an epistemological strike against, at least the _prima facie_ appeal of, active externalism. It is shown here however that, contrary to pretheoretical intuitions, neither the extended cognition _nor_ the extended mind theses are in principle (...) incompatible with two prominent versions of epistemic internalism—viz., accessibilism and mentalism. In fact, one possible diagnosis is that pretheoretical intuitions regarding the incompatibility of active externalism with epistemic internalism are symptomatic of a tacit yet incorrect identification of epistemic internalism with epistemic individualism. Thus, active externalism is not in principle incompatible with epistemic internalism per se and does not significantly restrict one’s options in epistemology. (shrink)

Jeff Paris proves a generalized Dutch Book theorem. If a belief state is not a generalized probability then one faces ‘sure loss’ books of bets. In Williams I showed that Joyce’s accuracy-domination theorem applies to the same set of generalized probabilities. What is the relationship between these two results? This note shows that both results are easy corollaries of the core result that Paris appeals to in proving his dutch book theorem. We see that every point of accuracy-domination defines a (...) dutch book, but we only have a partial converse. (shrink)

A new theory that naturalizes biological function is explained and compared with earlier etiological and causal role theories. Etiological theories explain functions from how they are caused over their evolutionary history. Causal role theories analyze how functional mechanisms serve the current capacities of their containing system. The new proposal unifies the key notions of both kinds of theories, but goes beyond them by explaining how functions in an organism can exist as factors with autonomous causal efficacy. The goal-directedness and normativity (...) of functions exist in this strict sense as well. The theory depends on an internal physiological or neural process that mimics an organism’s fitness, and modulates the organism’s variability accordingly. The structure of the internal process can be subdivided into subprocesses that monitor specific functions in an organism. The theory matches well with each intuition on a previously published list of intuited ideas about biological functions, including intuitions that have posed difficulties for other theories. (shrink)

The research aims to identify the status of the application of electronic document management system in governmental institutions – the study was applied on the Palestinian Pension Agency. The population of this study is composed of all employees in the Palestinian Pension Agency. In order to achieve the objectives of the study, the researchers used the descriptive and analytical approach, through which try to describe the phenomenon of the subject of the study, analyze the data and the relationship between the (...) components and the views put around it. Census method was used due to the small size of the study population and ease of access to the target group. (108) questionnaires were distributed to all members of the study population, were (65) employees in the Gaza Strip and (43) employees in the West Bank. All questionnaires were recovered. The study found the following results: There were no statistically significant differences in the members of the population in response to differences in the study about the reality of the application of electronic document management system in governmental institutions - case study on the Palestinian Pension Authority due to the age. There are no statistically significant differences in population members in response to the reality of the application of electronic document management system in governmental institutions - case Study on the Palestinian Pension Authority due to the variable nature of the job. As well as there are no statistically significant differences in the members of the population in response to the study about the reality of the application of electronic document management system in governmental institutions - case study on the Palestinian Pension Authority due to the variable of specialization. There are statistically significant differences in the study about the reality of the application of electronic document management system in governmental institutions - case study on the Palestinian Pension Authority due to Qualification variable for the benefit of members of the population study who are holding a Bachelor degree. There are statistically significant differences in the study about the reality of the application of electronic document management system in governmental institutions – case study on the Palestinian Pension Authority due to the variable number of years of experience for the benefit of members of the study population who have experience between 11-15 years. The study found a group of recommendations, including: the need to focus on the establishment of a general management of electronic documents in the organization structure that takes care of all the technical processes in it an contains scientifically qualified persons in the field of electronic document management. The need is for the attention in developing strategic plans, policies and mechanisms of action commensurate with the electronic document management system. (shrink)

The higher-order thought (HOT) theory of consciousness is a reductive representational theory of consciousness which says that what makes a mental state conscious is that there is a suitable HOT directed at that mental state. Although it seems that any neural realization of the theory must be somewhat widely distributed in the brain, it remains unclear just how widely distributed it needs to be. In section I, I provide some background and define some key terms. In section II, I argue (...) against the view that HOT theory should treat first-order (i.e. world-directed) conscious states as requiring prefrontal cortical activity though it is reasonable to suppose that conscious states are realized in the brain. In section III, I then explore some of the key background metaphysical issues involved in understanding the nature of consciousness, such as the debate between realism and idealism as well as the prospects for solving the so-called “hard problem” of consciousness. Some of the differences in question often mirror the traditional differences between Western and Eastern perspectives on the nature of consciousness. Overall, I argue that some form of realism and physicalism is more plausible than the opposing views. I also argue that materialists (and especially HOT theorists) can offer plausible replies to the hard problem. (shrink)

In the literature on supervaluationism, a central source of concern has been the acceptability, or otherwise, of its alleged logical revisionism. I attack the presupposition of this debate: arguing that when properly construed, there is no sense in which supervaluational consequence is revisionary. I provide new considerations supporting the claim that the supervaluational consequence should be characterized in a ‘global’ way. But pace Williamson (1994) and Keefe (2000), I argue that supervaluationism does not give rise to counterexamples to familiar inference-patterns (...) such as reductio and conditional proof. (shrink)

Interpersonal aggregation involves the combining and weighing of benefits and losses to multiple individuals in the course of determining what ought to be done. Most consequentialists embrace thoroughgoing interpersonal aggregation, the view that any large benefit to each of a few people can be morally outweighed by allocating any smaller benefit to each of many others, so long as this second group is sufficiently large. This would permit letting one person die in order to cure some number of mild headaches (...) instead. Most non-consequentialists reject thoroughgoing interpersonal aggregation despite also believing it is permissible to let one person die in order to prevent many cases of paraplegia instead. Non-consequentialists defend this asymmetry largely on the basis of intuition, and some rely on the notion of relevance to formalize the grounding intuitions. This article seeks to clarify and strengthen the non-consequentialist notion of relevance by engaging with three objections to it. (shrink)

In this paper we describe a few interrelated issues for validating theories that posit levels of consciousness. First, validating levels of consciousness requires consensus about the ordering of conscious states, which cannot be easily achieved. This problem is particularly severe if we believe conscious states can be irreducibly smeared over time. Second, the relationship between conscious states is probably sometimes intransitive, which means levels of consciousness will not be amenable to a single continuous measure. Finally, even if a multidimensional approach (...) to levels of consciousness is adopted, we argue that there are further problems for its validation. (shrink)

Abstract - The aim of the study is to identify the degree of administrative transparency in the Palestinian higher educational institutions in the Gaza Strip. In the study, the researchers adopted a descriptive and analytical method. The research population consisted of administrative staff, whether academic or administrative, except for those in senior management or the university council. The study population reached 392 employees. A random sample was selected (197). The number of questionnaires recovered was (160) with a recovery rate of (...) (81.2%). The researchers used a questionnaire for the data collection and were treated using SPSS to obtain the results. The results show that there is no significant difference between male responses and female responses due to gender variable. The results also confirm that there is no significant difference between respondents' responses due to the age variable. The results also showed a significant difference between respondents' responses attributed to the university variable. There is a fundamental difference between respondents' responses attributed to the scientifically qualified variable. The results also confirmed a significant difference between respondents' responses attributed to the management level variable. The results also confirmed a significant difference between respondents' responses due to variable years of service. The research reached a number of recommendations, the most important of which is: The necessity of Palestinian universities to adhere to the application of transparency standards in all university activities. The need to benefit from regional and international experience in the application of transparency systems within universities and to examine the possibility of applying these systems in our universities. As well as the need to engage in the program of teaching transparency in universities, as it is confirmed that only five universities participated in this experiment. The importance of raising awareness among the employees of Palestinian universities to clarify the foundations of building transparency and its dimensions to represent the active supporter through workshops and seminars. (shrink)

I advance a type of conceptualist argument for substance dualism – minimally, the view that we are spiritual substances that have bodies – based on the understandability of what it would be for something to be a spirit, e.g. what it would be for God to be a spirit. After presenting the argument formally, I clarify and defend its various premises with a special focus on what I take to be the most controversial one, namely, if thinking matter is metaphysically (...) possible, it is not the case that we have a distinct positive concept of God's being a divine spirit. (shrink)

Contemporary discussion concerning institutions focus on, and mostly accept, the Searlean view that institutional objects, i.e. money, borders and the like, exist in virtue of the fact that we collectively represent them as existing. A dissenting note has been sounded by Smit et al. (Econ Philos 27:1–22, 2011), who proposed the incentivized action view of institutional objects. On the incentivized action view, understanding a specific institution is a matter of understanding the specific actions that are associated with the institution and (...) how we are incentivized to perform these actions. In this paper we develop the incentivized action view by extending it to institutions like property, promises and complex financial organisations like companies. We also highlight exactly how the incentivized action view differs from the Searlean view, discuss the method appropriate to such study and discuss some of the virtues of the incentivized action view. (shrink)

Much of the philosophical literature on health inequalities seeks to establish the superiority of one or another conception of luck egalitarianism. In recent years, however, an increasing number of self-avowed egalitarian philosophers have proposed replacing luck egalitarianism with alternatives that stress the moral relevance of distinct relationships, rather than the moral relevance of good or bad luck. After briefly explaining why I am not attracted to luck egalitarianism, I seek in this chapter to distinguish and clarify three views that have (...) been characterized in the philosophical literature as forms of relational egalitarianism. I call these three relational views equality of treatment, equality of concern, and social egalitarianism. I will explain why each claims to be a form of egalitarianism and why these three views should not be seen as competitors. I will argue that each brand of relational egalitarianism describes a plausible plank of distributive justice that bears on the evaluation of health inequalities and on the political institutions that create, sustain, or exacerbate them. To illustrate this pluralistic relational egalitarian approach, I will draw on a case study by Horton and Barker (this volume) to discuss how each of the three planks might be brought to bear on the evaluation of oral health disparities among the children of migrant Latino farmworkers in California. (shrink)

Translated into Danish by Henrik Jøker Bjerre.

In this short paper I will introduce an idea which, I will argue, presents a fundamental additional challenge to the machine consciousness community. The idea takes the questions surrounding phenomenology, qualia and phenomenality one step further into the realm of intersubjectivity but with a twist, and the twist is this: that an agent’s intersubjective experience is deeply felt and necessarily co-affective; it is enkinaesthetic, and only through enkinaesthetic awareness can we establish the affective enfolding which enables first the perturbation, and (...) then the balance and counter-balance, the attunement and co-ordination of whole-body interaction through reciprocal adaptation. (shrink)

Our folk epistemology says that if someone knows that P and tells you that P, then, given the absence of defeaters, if you believe what they tell you, you will come to know that P as well. A speaker's knowledge that P is then, for the most part, enough for a hearer to come to know that P. But there are counterexamples to this principle: testimonial knowledge does not always transfer from the speaker to the hearer. Why should that be (...) so? Because testimonial knowledge arises through the flow of information--from conclusive grounds--from the speaker through the speaker's assertion to the hearer's state of comprehension as of the speaker's assertion. A speaker's belief can be based on conclusive grounds, but the speaker's assertion may fail to provide conclusive grounds to the hearer. Then the hearer won't acquire knowledge, even from a knowledgeable speaker. Knowledge from testimony then works more like knowledge through perception. But wait, you say, that can't be so because testimony involves free will but perception does not. The essay ends with a broadly Hume inspired reply to this objection. (shrink)

Linda Zagzebski’s book on epistemic authority is an impressive and stimulating treatment of an important topic. 1 I admire the way she manages to combine imagination, originality and argumentative control. Her work has the further considerable merit of bringing analytic thinking and abstract theory to bear upon areas of concrete human concern, such as the attitudes one should have towards moral and religious authority. The book is stimulating in a way good philosophy should be -- provoking both disagreement and emulation. (...) I agree with much of what she says, and have been instructed by it, but it will be of more interest and relevance here if I concentrate upon areas of disagreement. Perhaps they are better seen as areas, at least some of them, where her emphases suggest a position that seems to me untenable, but that she may not really intend. In that event, I will be happy to have provoked a clarification or the dispelling of my misunderstanding. My focus will be upon problems in her account of communal authority and autonomy, especially with respect to religious and political authority. Here my worry is that she places too much trust in trust and not enough in what I call selective mistrust. (shrink)

In this paper a parallel is drawn between the problem of epistemic access to abstract objects in mathematics and the problem of epistemic access to idealized systems in the physical sciences. On this basis it is argued that some recent and more traditional approaches to solving these problems are problematic.

In a series of well known publications, Christine Korsgaard argues for the claim that an agent acts morally just in case s/he acts autonomously. Two of Korsgaard's signature arguments for the connection between morality and autonomy are the "argument from spontaneity" and the "regress argument." In this paper, I argue that neither the argument from spontaneity nor the regress argument is able to show that an agent would be acting wrongly even if s/he acts in a paradigmatically heteronomous fashion.

This paper presents a corrected version of Pascal's wager that makes it consonant with modern decision theory. The corrected wager shows that not committing to God's existence is the rational choice.

It has been objected recently that naïve realism is inconsistent with an empirically well-supported hypothesis that unconscious perception is possible. Because epistemological disjunctivism is plausible only in conjunction with naïve realism (for a reason I provide), the objection reaches it too. In response, I show that the unconscious perception hypothesis can be changed from a problem into an advantage of epistemological disjunctivism. I do this by suggesting that: (i) naïve realism is consistent with the hypothesis; (ii) the contrast between epistemological (...) disjunctivism and epistemic externalism explains the difference in epistemic import between conscious and unconscious perception. (shrink)