Omissions are sometimes linked to responsibility. A harm can counterfactually depend on an omission to prevent it. If someone had the ability to prevent a harm but didn’t, this could suffice to ground their responsibility for the harm. Michael S. Moore’s claim is illustrated by the tragic case of Peter Parker, shortly after he became Spider-Man. Sick of being pushed around as a weakling kid, Peter became drunk on the power he acquired from the freak bite of a radioactive (...) spider. When a police officer called to Spider-Man to stop an escaping burglar, which he could have done easily, he failed to act. He was through taking orders. The omission was followed by a crime. That very same burglar later robbed Peter’s own house and when challenged he shot dead Peter’s Uncle Ben. Later, Spider-Man tracked down the killer and, when seeing his face close up, the possibility of prevention dawned on him. He could have stopped this crook and had he done so Uncle Ben would still be alive. Stan Lee’s tale of power finished with a Shakespearean twist. Young Peter realised the truth of the WGPCGR-thesis: With Great Power Comes Great Responsibility. We too will endorse the WGPCGR-thesis. There is a close connection between our notions of moral and legal responsibility and the powers we have as causal agents. This will be particularly important when it comes to the case of omissions: where we had the power to act but failed to do so. We hope to show the connections between the notions of power, cause, act, omission and responsibility but also some of the nuances. We will do so with particular reference to Moore’s account in Causation and Responsibility. (shrink)

DESENVOLVIMENTO EMBRIONÁRIO E DIFERENCIAÇÃO SEXUAL -/- E. I. C. da Silva Departamento de Agropecuária – IFPE Campus Belo Jardim Departamento de Zootecnia – UFRPE sede -/- 1.1 INTRODUÇÃO O sexo foi definido como a soma das diferenças morfológicas, fisiológicas e psicológicas que distinguem o macho da fêmea permitindo a reprodução sexual e assegurando a continuidade das espécies. Os processos de diferenciação sexual são realizados durante o desenvolvimento embrionário, onde ocorre a proliferação, diferenciação e maturação das células germinativas e primordiais, precursoras (...) de ovócitos e espermatozoides em fêmeas e machos, respectivamente. Assim, os embriões machos e fêmeas iniciam o seu desenvolvimento de forma semelhante, de modo que em ambos os sexos se estabelecem em estruturas idênticas a partir das quais se formarão os órgãos reprodutores correspondentes a cada sexo. O conhecimento da origem e do desenvolvimento do aparelho genital é indispensável para entender sua função e as alterações que produzem infertilidade ou esterilidade. 1.2 DETERMINAÇÃO DO SEXO CROMOSSÔMICO Nos mamíferos, o sexo cromossômico é determinado no momento da fertilização, quando um óvulo, que contém um cromossomo X, é fecundado por um espermatozoide portador de um cromossomo X ou um cromossomo Y. No primeiro caso, o complemento cromossômico seria XX, o que originaria uma fêmea (sexo homogamético), e no segundo daria como resultado um macho com a fórmula cromossômica XY (sexo heterogâmico). 1.3 A GÔNADA INDIFERENCIADA A primeira manifestação das gônadas se aprecia no embrião em forma de um par de eminências longitudinais chamadas cristas ou dobras gonodais, situadas em ambos os lados da linha média entre os mesonefros (rins em desenvolvimento) e do mesentério dorsal. Nos embriões dos mamíferos, as células germinativas primordiais (CGP) manifestam-se em estágios precoces do desenvolvimento, podendo ser detectadas pela primeira vez na metade da gastrulação. As CGP são células grandes, de citoplasma claro e núcleo grande e redondo, localizadas na parede do saco vitelino, perto do alantoide. Essas células possuem grande capacidade de proliferação e vão migrar desde o endoderma do intestino e o epitélio do saco vitelino, através do mesentério, até as cristas gonodais. Isso ocorre por volta do 26° dia da gestação no bovino. Sua migração realiza-se graças aos movimentos de translocação passiva e deslocamento ameboide ativo. Desconhece-se o mecanismo pelo qual estas células são dirigidas para as cristas gonodais, porém foram estudadas algumas moléculas que se expressam durante sua migração e que poderiam desempenhar um papel importante na diferenciação deste tipo celular. A fosfatase alcalina é uma enzima que tem sido usada como marcador de CGP para determinar a sua origem e migração. Num estudo recente, foi inserido um marcador fluorescente que se exprime unicamente nas células germinativas primordiais de embriões transgênicos, e utilizando este marcador e a fosfatase alcalina determinou-se a origem e o padrão de migração destas células. O primeiro sinal de diferenciação das células germinativas primordiais é a expressão de fosfatase alcalina, e esta apareceu pela primeira vez na parte mais posterior da linha primitiva. No sétimo dia de desenvolvimento no embrião do camundongo, o endoderma visceral (AF+) é substituído pelo endoderma definitivo (AF-) originado na parte anterior da linha primitiva. O fator de transcrição Oct-4 é expresso nas CGP de ambos os sexos, pelo que acredita-se estar envolvido na mantença a totipotêncialidade das células. O receptor tirosina quinase, cujo ligante é o fator de Steel, é outra das moléculas que expressam as CGP. Tem sido demonstrado que este receptor possui um papel muito importante na sobrevivência deste tipo celular. Existem outros fatores que promovem a sobrevivência e/ou proliferação de CGP in vitro. Em experiências realizadas com o fator de transformação beta I (TGFβ-I), observou-se que este tem um efeito negativo sobre a proliferação das CGP. Outra atividade que tem sido postulada a este fator é o de um agente quimioatraente que possivelmente possa direcionar a migração destas células para a gônada. a) Um formado pelas células germinativas primordiais (precursoras dos gametas masculinos ou femininos), rodeadas de células somáticas das quais posteriormente se derivarão as células de Sertoli no macho e as células da granulosa na fêmea. b) O tecido que formará o estroma da gônada: tecido conjuntivo, vasos sanguíneos e as células intersticiais com atividade esteroidogênica (células de Leydig no testículo e a teca interna do ovário). As células somáticas do primórdio gonodal originam-se do mesoderma. Inicialmente são de três tipos: mesenquimáticas, mesoteliais e endoteliais. As células mesenquimáticas e mesoteliais iniciam grande atividade proliferativa ao chegar as CGP. Observa-se então uma condensação de células de origem mesotelial e mesenquimatoso que forma um agregado compacto denominado "blastema gonodal". A partir deste primórdio embrionário, diferenciam-se dois tecidos gonodais: os cordões sexuais e o estroma. Os cordões sexuais são arranjos epiteliais que se encontram delimitados por uma folha basal, e dentro deles encontramos as CGP. Por sua vez, no estroma encontram-se células do tipo mesenquimático e vasos sanguíneos. Neste momento, as gônadas são indiferenciadas e bipotencialmente sexuais, sendo impossível diferenciar, morfologicamente, uma gônada masculina de uma feminina, mas no caso dos machos genéticos já existe uma diferenciação da gônada a nível molecular. Nesta fase já se encontram presentes as estruturas das quais se desenvolvem os dutos mesonéfricos ou de Wolff precursores do aparelho genital masculino e os dutos paramesonéfricos ou de Müller que darão origem ao aparelho reprodutor feminino. Há uma série de fatores envolvidos no desenvolvimento precoce da gônada, entre os quais o fator esteroidogênico I (SFI: Steroidogenic fator l), que é um membro da subfamília de receptores nucleares, receptores órfãos. Este fator de transcrição tem um local de ligação ao DNA composto por dois dedos-de-Zinc. O SFI foi identificado como um ativador de genes envolvidos na biossíntese de esteroides em diferentes células. O SFI está presente durante o desenvolvimento embrionário em regiões associadas com funções endócrinas como gônadas, adrenais, pituitárias e hipotálamos. Os animais homozigotos para o gene SFI defeituoso, necessitam de gônadas e adrenais e têm a função gonadotrófica alterada. Os ratos sem SFI carecem de gonadotrofos e têm um desenvolvimento anormal do núcleo ventro-medial do hipotálamo; em particular as gônadas deixam de se desenvolver entre os dias 11 a 15 e degeneram-se por apoptose. No entanto, a crista genital forma-se e é colonizada pelas células germinativas, o que indica que estas continuam a receber o sinal adequado para a sua migração. Portanto, o SFI não está envolvido no desenvolvimento precoce da gônada e do sistema urogenital, mas parece estar envolvido na manutenção do crescimento das células somáticas presentes na gônada indiferenciada. O gene associado ao tumor de Wilms (WTI: Wilm's tumor Associated) está envolvido no desenvolvimento da gônada e do rim. Durante o desenvolvimento embrionário, WTI se expressa em todo o mesoderma intermediário e posteriormente na gônada indiferenciada, bem como no rim em formação. WTI regula o sinal indutivo do mesênquima para o epitélio celômico dos mesonefros. Se este for o caso, então WTI é responsável pelo crescimento da crista genital ao dirigir a entrada do epitélio celômico. Dado que estas células darão origem às células de Sertoli, a carência de WTI pode causar o desenvolvimento de embriões XY como fêmeas simplesmente porque não se formam as células de Sertoli. Em geral, todos os genes importantes na diferenciação do mesoderma intermediário e do sistema urogenital intervêm no desenvolvimento da gônada precoce. 1.4 DIFERENCIAÇÃO GONODAL O desenvolvimento das gônadas e ductos genitais descritos até o momento, é o mesmo para ambos os sexos. Igualmente, os genes descritos, que estão envolvidos no desenvolvimento das gônadas, ductos genitais e migração das células germinativas, afetam igualmente os embriões com genótipo XX ou XY. A gônada primitiva consiste anatomicamente de uma medula (interna) e uma crosta (externa), e de acordo com o local onde ocorre a colonização das células germinativas, diferenciara em testículo ou um ovário, respectivamente. Nos mamíferos, a primeira manifestação estrutural de diferenciação sexual é detectada na gônada dos machos, onde as células germinativas estão localizadas na medula. A diferenciação do testículo inicia-se quando os cordões sexuais se separam do epitélio celômico como consequência dos arranjos produzidos por uma invasão do mesênquima e vasos sanguíneos que provoca a compactação dos cordões, agora denominados cordões testiculares. As células que rodeiam os cordões se achatam e formam as células mioides, que são responsáveis pela formação das membranas basais. As células do epitélio interno, ou seja, as células de Sertoli, têm duas funções principais: o suporte das CGP e a síntese da hormona antimulleriana, responsável pela regressão dos ductos de Müller e secretada durante o período de diferenciação sexual. As células do estroma que rodeiam os cordões testiculares diferenciam-se para formar vários tipos de células: células mioides, fibroblastos, endotélio e células de Leydig, que são as mais importantes pela sua atividade endócrina. Posteriormente, os cordões testiculares dão origem aos túbulos seminíferos, que contêm o epitélio que produzirá os espermatozoides ao chegar à puberdade. Na fêmea, durante os estágios iniciais de diferenciação gonodal, não se observam mudanças em relação à gônada indiferenciada, só pode-se observar um certo crescimento devido à proliferação de células somáticas e germinativas. As células germinativas iniciam um período de proliferação, que termina com o início da meiose. Iniciada a meiose, dá-se o processo de foliculogênese; neste momento os cordões epiteliais se fragmentam, de tal maneira que cada ovócito fica rodeado de células epiteliais cobertas por uma folha basal fina (figura 1). Para que a gônada primitiva se desenvolva em testículo é indispensável a presença do cromossoma Y, independentemente do número de cromossomas X que contenha o genoma de um indivíduo. O gene determinante do testículo encontra-se localizado no cromossoma Y, denominado sry em ratos e SRY em humanos. O gene sry se expressa durante o desenvolvimento embrionário na crista genital de embriões de camundongos. A expressão é detectável no dia 10,5, pouco depois do aparecimento das cristas genitais, atinge o seu máximo durante o dia 11,5 e mantém-se até pouco depois de ocorrerem os primeiros sinais morfológicos de diferenciação testicular no dia 12,5. Este padrão de expressão é compatível com a teoria de que sry atua induzindo a ativação dos genes (figura 2) que conduzem ao desenvolvimento testicular, sem que exista a necessidade da expressão contínua de sry para manter a diferenciação do testículo após o dia 12,5. Como mencionado anteriormente, a gônada primitiva é composta por vários tipos de células. No entanto, as células germinativas primordiais não são o local de expressão do sry, já que os embriões que necessitam de células germinativas mantêm a expressão de sry e desenvolvem o sexo gonodal normalmente. As células somáticas na gônada em desenvolvimento incluem também as células de suporte. Sabe-se que é nestas células que o sry é expresso para que se diferenciem em células de Sertoli, e a expressão transitória de sry indica que deve ativar a outros genes para a manutenção das células de Sertoli. Uma vez diferenciadas as células de Sertoli, elas se encarregarão da diferenciação do resto das células na gônada. -/- Figura 1: Representação da diferenciação dos órgãos genitais internos. Adaptado de BRONSON, 1989. Figura 2: Cascada de genes envolvidos na diferenciação sexual, adaptado de KOOPMAN, 1999. O fator sry é necessário para a diferenciação do testículo. Embora não se conheçam os genes que provavelmente regulam esse gene, estudos realizados em camundongos demonstram que este gene parece coordenar-se com certos genes autossômicos. Entre estes genes autossômicos, o sox9, que é produzido pelas células de Sertoli uma vez que são estimuladas por sry, de modo que sox9 é um dos genes relacionados estruturalmente com sry. O Sox9 funciona como um fator de transcrição, mas não se sabe se a proteína tem qualquer outra função estrutural; este gene exprime-se abundantemente nos condrócitos e está relacionado com defeitos do aparelho ósseo chamados displasia campomélica. Curiosamente, os pacientes XY com esta condição sofrem frequentemente de reversão do sexo. O Sox9 é um dos poucos genes, além do SRY, do qual as mutações demonstraram interferir com a determinação sexual masculina. No entanto, apenas 75% dos pacientes com anomalias esqueléticas de tipo displasia campomélica têm reversão sexual e não foram encontrados casos de reversão sexual devido a um defeito de Sox9 que não seja acompanhado de defeitos esqueléticos. Isso indica que o Sox9 é apenas um membro da rede de genes que são ativados para determinar a diferenciação sexual, enquanto a rota que rege a condrogênese é mais sensível a perturbações deste. O momento em que se detecta a expressão do gene Sox9 (11dpc em ratos) coincide com a máxima expressão de sry, o que poderia indicar a possibilidade de que sry regule positivamente a Sox9. De fato, na região do promotor de Sox9 há um local de união ao que potencialmente se pode unir o sry. A expressão de Sox9 durante a diferenciação sexual sugere um papel abaixo de sry na diferenciação das células de Sertoli. O cromossoma X também é importante na diferenciação gonodal. O gene DAX-I foi isolado do lócus DSS (Dosage sensitive sex reversal) do cromossoma X. DAX-I é parte da cascata de determinação sexual, mas não é necessário para a formação do testículo. DAX-I é um membro dos receptores nucleares conhecidos como receptores órfãos. Este gene demonstrou ser um poderoso repressor da transcrição de SFI e de vários genes. Os padrões de expressão de DAX-I são complementares daqueles de SFI, ambos expressos nas cristas genitais. Em resumo, dada a evidência exposta, desenvolveu-se a hipótese de que DAX-I é um antagonista de sry; esse antagonismo é dependente dos níveis relativos de DAX-I e sry e de um limiar que varia de espécie para espécie. A DAX-I foi classificada como o gene antitestículo. Na fêmea (cariótipo XX) é importante que ocorra a inativação de um dos cromossomas sexuais X para que se mantenha o equilíbrio genético ao igualar o conteúdo de DNA dos cromossomas. Esse cromossoma inativado constitui o chamado corpúsculo de Barr. No entanto, para que a meiose se realize, é necessário dos dois cromossomas X ativos nos ovócitos para assegurar a diferenciação ovárica e a fertilidade. 1.5 DIFERENCIAÇÃO DOS DUCTOS SEXUAIS O embrião possui, além das gônadas indiferenciadas, dois sistemas de ductos: os de potencialidade masculina denominam-se ductos de Wolff ou mesonéfricos, e os de potencialidade feminina se chamam ductos de Müller ou paramesonéfricos (figura 1). Se a diferenciação gonodal levou à formação de um testículo, a partir do ducto mesonéfrico ou de Wolff se desenvolverão os ductos eferentes, o epidídimo, os ductos deferentes e as vesículas seminais. As hormonas importantes no desenvolvimento do aparelho genital masculino são a testosterona, produzida pelas células de Leydig, e sua forma 5α reduzida, a 5α di-hidrotestosterona. Acredita-se que a testosterona é responsável pela virilização dos ductos de Wolff, e a di-hidrotestosterona dos órgãos genitais externos. No macho, os canais de Müller atrofiam-se devido à ação de uma hormona fetal de origem testicular denominada hormona inibidora das estruturas de Müller (HIM) ou hormona antimulleriana. Este processo começa assim que os cordões espermáticos se formam e se diferenciam as células de Sertoli. A existência de HIM foi proposta baseada em estudos realizados em bezerras freemartin, devido à existência de uma hormona responsável pela atresia dos ductos de Müller que na fêmea dá origem ao útero e aos ovidutos. Essa hormona provoca a involução do aparelho genital do bovino nas gestações gemelares nas quais os produtos de diferente sexo têm comunicação sanguínea por ter ocorrido a anastomose dos vasos de ambas as placentas (figura 3). A HIM é uma glicoproteína pertencente à subfamília de TGFβ, é expressa pelas células que darão origem às células de Sertoli e é um dos primeiros marcadores de diferenciação nestas células. A HIM é secretada na vida adulta pelas células de Sertoli no testículo e por células da granulosa no ovário. No rato a HIM é expressa-se no 12° dia em um teste padrão que segue muito de perto o aumento na expressão de sry. No macho, esta secreção de HIM continua durante a vida fetal e adulta, contudo os níveis de HIM declinam na puberdade devido a um aumento na secreção de testosterona. Vários fatores intervêm na regulação do gene de HIM, incluindo os acima descritos SFI e Sox9. O gene HIM contém segmentos de DNA que são conservados em várias espécies de vertebrados. Existe um nexo de ligação para SFI, que ativa a transcrição de HIM. A mutação no local de ligação de SFI resulta em reversão do sexo em indivíduos XY incluindo genitais femininos normais, presença de um útero formado enfatizando a importância de SFI na determinação sexual e na expressão de HIM. Embora SFI seja um bom candidato como regulador de HIM, é expresso em outras células, como as de Leydig e adrenais, que não expressam HIM. Em contrapartida, Sox9 é expresso unicamente nas células de Sertoli que são as produtoras de HIM. O gene HIM também tem um nexo de ligação para Sox9. Além disso, Sox9 pode atuar sinergicamente com SFI para promover a secreção de HIM. Ao contrário destes dois fatores de transcrição, DAX-I antagoniza a ação de Sox9 e provavelmente SFI sobre o promotor de HIM. Assim, para que as células de Sertoli secretem HIM, a transcrição de DAX-I deve diminuir. Figura 3: Representação da diferenciação dos órgãos genitais externos. Adaptado de BRONSON, 1989. Os ductos de Wolff tornam-se o sistema de ejaculação do macho. A porção mais próxima dos testículos dá origem ao epidídimo, a parte central ao ducto deferente e a porção mais distal às vesículas seminais. A próstata e a parte membranosa da uretra do macho desenvolvem-se a partir da porção pélvica do seio urogenital. A virilização e diferenciação dos ductos de Wolff dependem da produção de testosterona pelo testículo. Quanto aos órgãos genitais externos do macho, o tubérculo genital é ampliado e as dobras uretrais se fundem para formar a uretra peniana. A fusão das dobras uretrais aproxima os tubérculos genitais para formar o escroto (figura 4). Figura 4: Diferenciação do aparelho genital da fêmea e do macho. Adaptado de KOOPMAN, 1989. A diferenciação dos órgãos genitais da fêmea ocorre de forma passiva, já que a ausência de testículos e por isso da hormona inibidora dos ductos de Müller (HIM), assim como dos andrógenos virilizantes, favorece o desenvolvimento dos ductos de Müller, enquanto os de Wolff sofrem atrofia. A porção cefálica dos ductos de Müller dá origem aos ovidutos, que na sua terminação caudal se fundem com o útero. O contato dos ductos de Müller com o seio urogenital induz uma intensa proliferação celular que resulta na formação da área uterovaginal localizado entre o seio urogenital e os ductos de Müller. As células do prato uterovaginal proliferam e aumentam a distância entre as duas estruturas criando o espaço que formará a vagina quando o prato é canalizado e forma um lúmen. Em contraste com o que ocorre no macho, na fêmea a maior parte do seio urogenital se mantém exposta na superfície da abertura onde desembocam a vagina e a uretra. O tubérculo urogenital da fêmea tem um crescimento limitado e forma o clitóris. A sequência de passos da diferenciação sexual do aparelho genital é resumida na tabela 1. Tabela 1: Destino em desenvolvimento dos rudimentos sexuais dos fetos macho e fêmea dos mamíferos -/- Rudimento sexual Macho Fêmea Gônada Testículo Ovário Ductos de Müller (Paramesonéfricos) Vestígios Útero, parte da vagina, ovidutos Ductos de Wolff (Mesonéfricos) Ductos eferentes deferentes, epidídimo, vesículas seminais Vestígios Seio urogenital Uretra, próstata, glândulas bulbouretrais Parte da vagina, uretra, vestíbulo, glândulas vestibulares Tubérculo genital Pênis Clitóris Pregas vestibulares Escroto Lábios vulvares Fonte: HAFEZ, 2004. 1.6 DIFERENCIAÇÃO SEXUAL DO HIPOTÁLAMO Os processos de diferenciação sexual não se limitam apenas às células somáticas do organismo do feto, mas incluem também os centros nervosos superiores do cérebro. Assim, da mesma maneira que a gônada e os ductos sexuais se desenvolvem para o tipo feminino ou masculino, propôs-se que o cérebro pode ser "masculinizado" ou permanecer "Feminizado". A diferenciação do hipotálamo vai depender do ambiente esteroidal do neonato e ocorre na fase perinatal. Estes eventos serão de grande transcendência na vida reprodutiva do indivíduo. Tanto a fêmea como o macho nascem com a capacidade de secreção de gonadotropinas de acordo com um padrão cíclico; contudo, no macho, a exposição do hipotálamo à ação dos andrógenos testiculares durante os primeiros dias da vida extrauterina provoca a masculinização, com o qual o hipotálamo do macho é programado para que a secreção de gonadotropinas se realize a um ritmo relativamente constante por parte da hipófise (secreção tônica). Na fêmea, tanto a secreção tônica como a cíclica se conservam. No entanto, observou-se que a injeção de testosterona ou o transplante de testículo na rata fêmea durante os primeiros dias de vida, suprime a sua futura atividade estral (secreção cíclica). Por outro lado, se os ovários forem transplantados para o rato macho normal castrado na idade adulta, o animal não desenvolve qualquer atividade cíclica, mas se os machos transplantados forem castrados ao nascer, o ovário é capaz de efetuar mudanças cíclicas e ovulações. Isto foi demonstrado em roedores, mas não em animais domésticos ou na espécie humana. Portanto, o padrão de secreção de gonadotropinas, seja cíclico ou tônico, não depende da hipófise, mas do hipotálamo e sua correta diferenciação. 1.7 CONCLUSÕES A maioria dos conhecimentos no campo da biologia do desenvolvimento e, muito especificamente, dos processos de diferenciação sexual têm sido originados de estudos relacionados com desordens congênitas, que na sua maioria devem-se a defeitos de genes específicos. A análise detalhada destas desordens permitiu entender alguns mecanismos endócrinos, moleculares e genéticos envolvidos na diferenciação sexual. A identificação do gene sry como determinante do testículo foi uma contribuição crucial e abriu as portas à compreensão dos mecanismos moleculares e celulares relacionados com o desenvolvimento do testículo. Se este gene não estiver presente, é criado um programa genético alternativo para levar a cabo a diferenciação gonodal para o ovário. Finalmente, devemos ter presente que é necessária uma correlação entre mudanças morfológicas e expressão de genes durante o desenvolvimento para entender os mecanismos relacionados com a diferenciação. -/- Apoio -/- Realização -/- REFERÊNCIAS BIBLIOGRÁFICAS ANDERSON, Robert et al. The onset of germ cell migration in the mouse embryo. Mechanisms of development, v. 91, n. 1-2, p. 61-68, 2000. AUSTIN, Colin Russell; SHORT, R. V. Reproduction in Mammals: Volume 1, Germ Cells and Fertilization. Londres: Cambridge University Press, 1972. BRONSON, Franklin H. Mammalian reproductive biology. Chicago: University of Chicago Press, 1989. BUEHR, Mia. The primordial germ cells of mammals: some current perspectives. Experimental cell research, v. 232, n. 2, p. 194-207, 1997. BYSKOV, Anne G. Differentiation of mammalian embryonic gonad. Physiological reviews, v. 66, n. 1, p. 71-117, 1986. CAPEL, Blanche et al. Migration of mesonephric cells into the mammalian gonad depends on Sry. Mechanisms of development, v. 84, n. 1-2, p. 127-131, 1999. CAPEL, Blanche. The battle of the sexes. Mechanisms of development, v. 92, n. 1, p. 89-103, 2000. DERIVAUX, Jules; BARNABÉ, Renato Campanarut. Reprodução dos animais domésticos. Zaragoza: Acribia, 1980. DOMENICE, Sorahia et al. Aspectos moleculares da determinação e diferenciação sexual. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 46, n. 4, p. 433-443, 2002. DONAHOE, Patricia K. et al. Mullerian inhibiting substance activity in bovine fetal, newborn and prepubertal testes. Biology of reproduction, v. 16, n. 2, p. 238-243, 1977. HAFEZ, Elsayed Saad Eldin; HAFEZ, B. Reprodução animal. São Paulo: Manole, 2004. HANLEY, Neil A. et al. Steroidogenic factor 1 (SF-1) is essential for ovarian development and function. Molecular and cellular endocrinology, v. 163, n. 1-2, p. 27-32, 2000. HIORT, Olaf; PAUL-MARTIN, H. The molecular basis of male sexual differentiation. European journal of endocrinology, v. 142, n. 2, p. 101-110, 2000. HOLY, Lubos; MARTÍNEZ JÚSTIZ, G. Colab. Biología de la reproducción bovina. Havana: Revolucionária, 1975. JOSSO, Nathalie et al. The role of anti-Müllerian hormone in gonadal development. Molecular and cellular endocrinology, v. 145, n. 1-2, p. 3-7, 1998. JOST, Alfred et al. Studies on sex differentiation in mammals. In: Proceedings of the 1972 Laurentian Hormone Conference. Londres: Academic Press, 1973. p. 1-41. KNOBIL, Ernst. Knobil and Neill's physiology of reproduction. EUA: Gulf Professional Publishing, 2006. KOFMAN ALFARO, S.; MERCHANT LARIOS, H.; PEREZ PALACIOS, G. Diferenciacion sexual. I. Bases biologicas del dimorfismo sexual. Rev. invest. clín, p. 349-59, 1982. KOOPMAN, Peter. Sry and Sox9: mammalian testis-determining genes. Cellular and Molecular Life Sciences CMLS, v. 55, n. 6-7, p. 839-856, 1999. MCDONALD, L. E. Veterinary endocrinology. Lea & Febiger, Philadelphia, Pa, 1969. MEIZEL, S.; JOHNSON, M. H. Development in mammals. MH Johnson, Ed, v. 3, p. 1-64, 1978. MELLO, Maricilda Palandi de; ASSUMPÇÃO, Juliana de G.; HACKEL, Christine. Genes envolvidos na determinação e diferenciação do sexo. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 49, n. 1, p. 14-25, 2005. -/- REFERÊNCIAS BIBLIOGRÁFICAS MERCHANT-LARIOS, H. Ovarian differentiation. The Vertebrate Ovary, p. 47-81, 1978. MIES FILHO, Antonio. Reprodução dos animais. Porto Alegre: Sulina, 1987. NEF, Serge; PARADA, Luis F. Hormones in male sexual development. Genes & Development, v. 14, n. 24, p. 3075-3086, 2000. PARKER, Keith L.; SCHEDL, Andreas; SCHIMMER, Bernard P. Gene interactions in gonadal development. Annual review of physiology, v. 61, n. 1, p. 417-433, 1999. SWAIN, Amanda; LOVELL-BADGE, Robin. Mammalian sex determination: a molecular drama. Genes & development, v. 13, n. 7, p. 755-767, 1999. WILHELM, Dagmar; PALMER, Stephen; KOOPMAN, Peter. Sex determination and gonadal development in mammals. Physiological reviews, v. 87, n. 1, p. 1-28, 2007. WILSON, Jean D.; GRIFFIN, James E.; GEORGE, Fredrick W. Sexual differentiation: early hormone synthesis and action. Biology of reproduction, v. 22, n. 1, p. 9-17, 1980. -/- Emanuel Isaque Cordeiro da Silva Belo Jardim, 07 de Maio de 2020. (shrink)

Default positions, predetermined starting points that aid in complex decision-making, are common in clinical medicine. In this article, we identify and critically examine common default positions in clinical ethics practice. Whether default positions ought to be held is an important normative question, but here we are primarily interested in the descriptive, rather than normative, properties of default positions. We argue that default positions in clinical ethics function to protect and promote important values in medicine—respect for persons, utility, and justice. Further, (...) default positions in clinical ethics may also guard against harm. Where default positions exist, there are epistemic burdens to overturn them. The person wishing to reject the default position, rather than the person endorsing it, bears this burden. The person who bears the burden of meeting the epistemic requirements must provide evidence proportional to the degree of harm the default position protects against. Default positions that protect against significant harm impose significant epistemic requirements to overturn. This asymmetry not only makes medical decision-making more economical but also serves to promote and protect certain values. The identification and analysis of common and recognizable default positions can help to identify other default positions and the conditions under which their associated epistemic requirements are met. The article concludes with considerations of potential problems with the use of default positions in clinical ethics. (shrink)

The practice of medicine frequently involves the unconsented restriction of liberty. The reasons for unilateral liberty restrictions are typically that being confined, strapped down, or sedated are necessary to prevent the person from harming themselves or others. In this paper, we target the ethics of chemical restraints, which are medications that are used to intentionally restrict the mental states associated with the unwanted behaviors, and are typically not specifically indicated for the condition for which the patient is being treated. Specifically, (...) we aim to identify the conditions under which chemical restraints are ethically permissible. It is wrong to assume that what is morally true of physical restraints is also true of chemical restraints. Our aim is thus to identify the conditions under which chemical restraints are permissible while distinguishing these conditions from those of the application of physical restraints. (shrink)

Epistemic burdens – the nature and extent of our ignorance (that and how) with respect to various courses of action – serve to determine our incentive structures. Courses of action that seem to bear impossibly heavy epistemic burdens are typically not counted as options in an actor’s menu, while courses of action that seem to bear comparatively heavy epistemic burdens are systematically discounted in an actor’s menu relative to options that appear less epistemically burdensome. That ignorance serves to determine what (...) counts as an option means that epistemic considerations are logically prior to moral, prudential, and economic considerations: in order to have moral, prudential, or economic obligations, one must have options, and epistemic burdens serve to determine our options. One cannot have obligations without doing some epistemic work. We defend this claim on introspective grounds. We also consider how epistemic burdens distort surrogate decision-making. The unique epistemology of surrogate cases makes the priority of the epistemic readily apparent. We then argue that anyone who accepts a principle similar to ought implies can is committed to the logical priority of the epistemic. We also consider and reject several possible counterarguments. -/- . (shrink)

It is plausible that current generations owe something to future generations. One possibility is that we have a duty to not harm them. Another possibility is that we have a duty to protect them. In either case, however, to satisfy the duties to future generations from environmental or political degradation, we need to engage in widespread collective action. But, as we are, we have a limited ability to do so, in part because we lack the self-discipline necessary for successful collective (...) action. Given that having an obligation hinges on being able to satisfy it, the apparent duty to future generations is at odds with our apparent inability to satisfy it. Thus, we either need to rethink our duties to future generations or rethink the nature of our abilities. I argue in this chapter that we should rethink the nature of our abilities. Specifically, we should enhance our self-discipline, which is distinct from enhancements of motivation, judgment, or emotion. Even the most intelligent, motivated, and empathetic actor is likely to slip up, which encourages others to withdraw their cooperation. Without the necessary self-discipline to sustain our public cooperative behavior, collective action is likely to fail, leaving us with one alternative: to abandon our duties to future generations. (shrink)

Many people find the manipulation of the human germline—editing the DNA of sperm or egg cells such that these genetic changes are passed to the resulting offspring—to be morally impermissible. In this paper, I argue for the claim that editing the human germline is morally permissible. My argument starts with the claim that outcome uncertainty regarding the effects of germline editing shows that the duty to not harm cannot ground the prohibition of germline editing. Instead, if germline editing is wrong, (...) it is wrong because it violates a duty to protect. However, we also have an epistemic duty to gather evidence regarding the effects of editing the human germline which overrides any moral duty to protect future generations. Thus, we have a duty to gather evidence regarding the effects of editing the human germline, which is to say that we have a duty to edit the human germline. (shrink)

It has recently been argued that a person’s moral judgments (about both their own and others’ actions) are constrained by the nature and extent of their relevant ignorance and, thus, that such judgments are determined in the first instance by the person’s epistemic circumstances. It has been argued, in other words, that the epistemic is logically prior to other normative (e.g., ethical, prudential, pecuniary) considerations in human decision-making, that these other normative considerations figure in decision-making only after (logically and temporally) (...) relevant ignorance has constrained the decision-maker’s menu of options. If this is right, then a person’s moral judgments in some set of circumstances should vary with their knowledge and ignorance of these circumstances. In this study, we test the hypothesis of the logical priority of the epistemic. We describe two experiments in which subjects’ knowledge and ignorance of relevant consequences were manipulated. In the second experiment, we also compared the effect of ignorance on moral judgments with that of personal force, a factor previously shown to influence moral judgments. We found broad empirical support for the armchair arguments that epistemic considerations are logically prior to normative considerations. (shrink)

Some theorists argue that moral bioenhancement ought to be compulsory. I take this argument one step further, arguing that if moral bioenhancement ought to be compulsory, then its administration ought to be covert rather than overt. This is to say that it is morally preferable for compulsory moral bioenhancement to be administered without the recipients knowing that they are receiving the enhancement. My argument for this is that if moral bioenhancement ought to be compulsory, then its administration is a matter (...) of public health, and for this reason should be governed by public health ethics. I argue that the covert administration of a compulsory moral bioenhancement program better conforms to public health ethics than does an overt compulsory program. In particular, a covert compulsory program promotes values such as liberty, utility, equality, and autonomy better than an overt program does. Thus, a covert compulsory moral bioenhancement program is morally preferable to an overt moral bioenhancement program. (shrink)

Recent work has defended “Euclidean” theories of set size, in which Cantor’s Principle (two sets have equally many elements if and only if there is a one-to-one correspondence between them) is abandoned in favor of the Part-Whole Principle (if A is a proper subset of B then A is smaller than B). It has also been suggested that Gödel’s argument for the unique correctness of Cantor’s Principle is inadequate. Here we see from simple examples, not that Euclidean theories of set (...) size are wrong, but that they must be either very weak and narrow or largely arbitrary and misleading. (shrink)

There is recent empirical evidence that personal identity is constituted by one’s moral traits. If true, this poses a problem for those who advocate for moral enhancement, or the manipulation of a person’s moral traits through pharmaceutical or other biological means. Specifically, if moral enhancement manipulates a person’s moral traits, and those moral traits constitute personal identity, then it is possible that moral enhancement could alter a person’s identity. I go a step further and argue that under the right conditions, (...) moral enhancement can constitute murder. I then argue that these conditions are not remote. (shrink)

A probability distribution is regular if no possible event is assigned probability zero. While some hold that probabilities should always be regular, three counter-arguments have been posed based on examples where, if regularity holds, then perfectly similar events must have different probabilities. Howson (2017) and Benci et al. (2016) have raised technical objections to these symmetry arguments, but we see here that their objections fail. Howson says that Williamson’s (2007) “isomorphic” events are not in fact isomorphic, but Howson is speaking (...) of set-theoretic representations of events in a probability model. While those sets are not isomorphic, Williamson’s physical events are, in the relevant sense. Benci et al. claim that all three arguments rest on a conflation of different models, but they do not. They are founded on the premise that similar events should have the same probability in the same model, or in one case, on the assumption that a single rotation-invariant distribution is possible. Having failed to refute the symmetry arguments on such technical grounds, one could deny their implicit premises, which is a heavy cost, or adopt varying degrees of instrumentalism or pluralism about regularity, but that would not serve the project of accurately modelling chances. (shrink)

Newton published his deduction of universal gravity in Principia (first ed., 1687). To establish the universality (the particle-to-particle nature) of gravity, Newton must establish the additivity of mass. I call ‘additivity’ the property a body's quantity of matter has just in case, if gravitational force is proportional to that quantity, the force can be taken to be the sum of forces proportional to each particle's quantity of matter. Newton's argument for additivity is obscure. I analyze and assess manuscript versions of (...) Newton's initial argument within his initial deduction, dating from early 1685. Newton's strategy depends on distinguishing two quantities of matter, which I call ‘active’ and ‘passive’, by how they are measured. These measurement procedures frame conditions on the additivity of each quantity so measured. While Newton has direct evidence for the additivity of passive quantity of matter, he does not for that of the active quantity. Instead, he tries to infer the latter from the former via conceptual analyses of the third law of motion grounded largely on analogies to magnetic attractions. The conditions needed to establish passive additivity frustrate Newton's attempted inference to active additivity. (shrink)

There is no uniquely standard concept of an effectively decidable set of real numbers or real n-tuples. Here we consider three notions: decidability up to measure zero [M.W. Parker, Undecidability in Rn: Riddled basins, the KAM tori, and the stability of the solar system, Phil. Sci. 70(2) (2003) 359–382], which we abbreviate d.m.z.; recursive approximability [or r.a.; K.-I. Ko, Complexity Theory of Real Functions, Birkhäuser, Boston, 1991]; and decidability ignoring boundaries [d.i.b.; W.C. Myrvold, The decision problem for entanglement, in: (...) R.S. Cohen et al. (Eds.), Potentiality, Entanglement, and Passion-at-a-Distance: Quantum Mechanical Studies fo Abner Shimony, Vol. 2, Kluwer Academic Publishers, Great Britain, 1997, pp. 177–190]. Unlike some others in the literature, these notions apply not only to certain nice sets, but to general sets in Rn and other appropriate spaces. We consider some motivations for these concepts and the logical relations between them. It has been argued that d.m.z. is especially appropriate for physical applications, and on Rn with the standard measure, it is strictly stronger than r.a. [M.W. Parker, Undecidability in Rn: Riddled basins, the KAM tori, and the stability of the solar system, Phil. Sci. 70(2) (2003) 359–382]. Here we show that this is the only implication that holds among our three decidabilities in that setting. Under arbitrary measures, even this implication fails. Yet for intervals of non-zero length, and more generally, convex sets of non-zero measure, the three concepts are equivalent. (shrink)

As the federal government distributed remdesivir to some of the states COVID-19 hit hardest, policymakers scrambled to develop criteria to allocate the drug to their hospitals. Our state, Michigan, was among those states to receive an initial quantity of the drug from the U.S. government. The disparities in burden of disease in Michigan are striking. Detroit has a death rate more than three times the state average. Our recommendation to the state was that it should prioritize the communities that bear (...) a disproportionate burden of suffering in the allocation of the new potential treatment. This recommendation is justified not only for new drugs with uncertain effects, but also for drugs of certain benefit or vaccines. For states with significant health disparities, such as Michigan, this allocation priority may help to repair them. In fact, any other allocation strategy may make them worse. (shrink)

Moral bioenhancement is the potential practice of manipulating individuals’ moral behaviors by biological means in order to help resolve pressing moral issues such as climate change and terrorism. This practice has obvious ethical implications, and these implications have been and continue to be discussed in the bioethics literature. What have not been discussed are the epistemological implications of moral bioenhancement. This article details some of these implications of engaging in moral bioenhancement. The argument begins by making the distinction between moral (...) bioenhancement that manipulates the contents of mental states and that which manipulates other, non-representational states. Either way, I argue, the enhanced moral psychology will fail to conform to epistemic norms, and the only way to resolve this failure and allow the moral bioenhancement to be effective in addressing the targeted moral issues is to make the moral bioenhancement covert. (shrink)

Objective: Evidence suggests people experience an oral size illusion and commonly perceive oral size inaccurately; however, the nature of the illusion remains unclear. The objectives of the present study were to confirm the presence of an oral size illusion, determine the magnitude (amount) and direction (underestimation or overestimation) of the illusion, and determine whether immediately prior crossmodal perceptual experiences affected the magnitude and direction. Design: Participants (N = 27) orally assessed 9 sizes of stainless steel spheres (1/16 in to 1/2 (...) in) categorized as small, medium, or big, and matched them with digital and visual reference sets. Each participant completed 20 matching tasks in 3 assessments. For control assessments, 6 oral spheres were matched with reference sets of same-sized spheres. For primer-control assessments, similar to control, 6 matching tasks were preceded by cross-modal experiences of the same-sized sphere. For experimental assessments, 8 matching tasks were preceded by a cross-modal experience of a differently sized sphere. Results: For control assessments, small and medium spheres were consistently underestimated, and big spheres were consistently overestimated. For experimental assessments, magnitude and direction of the oral size illusion varied according to the size of the sphere used in the cross-modal experience. Conclusion: Results seemed to confirm an oral size illusion, but direction of the illusion depended on the size of the object. Immediately prior cross-modal experiences influenced magnitude and direction of the illusion, suggesting that aspects of oral perceptual experience are dependent upon factors outside of oral perceptual anatomy and the properties of the oral stimulus. (shrink)

Some have suggested that certain classical physical systems have undecidable long-term behavior, without specifying an appropriate notion of decidability over the reals. We introduce such a notion, decidability in (or d- ) for any measure , which is particularly appropriate for physics and in some ways more intuitive than Ko's (1991) recursive approximability (r.a.). For Lebesgue measure , d- implies r.a. Sets with positive -measure that are sufficiently "riddled" with holes are never d- but are often r.a. This explicates Sommerer (...) and Ott's (1996) claim of uncomputable behavior in a system with riddled basins of attraction. Furthermore, it clarifies speculations that the stability of the solar system (and similar systems) may be undecidable, for the invariant tori established by KAM theory form sets that are not d-. (shrink)

Despite the lack of evidence for their effectiveness, the use of physical restraints for patients is widespread. The best ethical justification for restraining patients is that it prevents them from harming themselves. We argue that even if the empirical evidence supported their effectiveness in achieving this aim, their use would nevertheless be unethical, so long as well known exceptions to informed consent fail to apply. Specifically, we argue that ethically justifiable restraint use demands certain necessary and sufficient conditions. These conditions (...) are that the physician obtain informed consent for their application, that their application be medically appropriate, and that restraints be the least liberty-restricting way of achieving the intended benefit. It is a further question whether their application is ever medically appropriate, given the dearth of evidence for their effectiveness. (shrink)

As the science and technology of the brain and mind develop, so do the ways in which brains and minds may be surveilled and manipulated. Some cognitive libertarians worry that these developments undermine cognitive liberty, or “freedom of thought.” I argue that protecting an individual’s cognitive liberty undermines others’ ability to use their own cognitive liberty. Given that the threatening devices and processes are not relevantly different from ordinary and frequent intrusions upon one’s brain and mind, strong protections of cognitive (...) liberty may proscribe neurotechnological intrusions, but also ordinary intrusions. Thus, the cognitive libertarian position “hog-ties” others’ use of their own liberties. This problem for the cognitive libertarian is the same problem that ordinary libertarianism faces in protecting individual rights to property and person. But the libertarian strategies for resolving the problem don’t work for the cognitive libertarian. I conclude that the right to mental privacy is weaker than what cognitive libertarians want it to be. (shrink)

Contemporary scholarship is divided over whether Anselm maintains a version of Eudaemonism. The debate centers on the question of whether the will for justice only moderates the will for happiness or, instead, provides a distinct end for which to act. Because of two key passages, various scholars hold that Anselm maintained elements of medieval Eudaemonism. In this article, I argue that Anselm separates morality from happiness, and I provide a sketch of his alternative view. First, I argue against some recent (...) perspectives that Anselm maintained Eudaemonism. To do so, I provide a non-Eudaemonist reading of the two key passages and show how Eudaemonist readings are lacking in different respects. Second, I examine what this argument means for Anselm’s understanding of happiness and moral obligation. While there are some Eudaemonist themes in Anselm’s thinking, he flatly denies and revises aspects of the system. (shrink)

With essay deadlines looming for many of our students, Matt Parker relives some of the angst involved in writing philosophy. You’re not alone.

Humans are morally deficient in a variety of ways. Some of these deficiencies threaten the continued existence of our species. For example, we appear to be incapable of responding to climate change in ways that are likely to prevent the consequent suffering. Some people are morally better than others, but we could all be better. The price of not becoming morally better is that when those events that threaten us occur, we will suffer from them. If we can prevent this (...) suffering from occurring, then we ought to do so. That we ought to make ourselves morally better in order to prevent very bad things from happening justifies, according to some, the development and administration of moral enhancement. I address in this paper the idea that moral enhancement could give rise to moral transhumans, or moral post-persons. Contrary to recent arguments that we shouldn’t engender moral post-persons, I argue that we should. Roughly, the reasons for this conclusion are that we can expect moral post-persons to resemble the morally best of us, our moral exemplars. Since moral exemplars promote their interests by promoting the interests of others (or they promote others’ interests at the expense of their own) we can expect moral post-persons to pursue our interests. Since we should also pursue our own interests, we should bring about moral post-persons. (shrink)

Augustine’s privation theory of evil maintains that something is evil in virtue of a privation, a lack of something which ought to be present in a particular nature. While it is not evil for a human to lack wings, it is indeed evil for a human to lack rationality according to the end of a rational nature. Much of the literature on the privation theory focuses on whether it can successfully defend against counterexamples of positive evils, such as pain. This (...) focus of the discussion is not surprising, given that the privation theory is a theory about the nature of evil. But it is also a theory that protects venerable theological concerns, namely, that God is the good creator of everything, and that everything is good. It is the purpose of this article to further this discussion on both fronts. I argue that the counterexample of pain still defeats the privation theory despite the most recent defense. What is more, I suggest, this is not theologically disastrous. The individual who rejects the privation theory is not obligated to reject the theological theses which motivate it. To show how a rejection of the privation theory is a live option, I offer an alternative view of evil that also maintains these theological theses and encompasses both privative and positive evils. (shrink)

We aim to establish the following claim: other factors held constant, the relative weights of the epistemic burdens of competing treatment options serve to determine the options that patient surrogates pursue. Simply put, surrogates confront an incentive, ceteris paribus, to pursue treatment options with respect to which their knowledge is most adequate to the requirements of the case. Regardless of what the patient would choose, options that require more knowledge than the surrogate possesses (or is likely to learn) will either (...) be neglected altogether or deeply discounted in the surrogate’s incentive structure. We establish this claim by arguing that the relation between epistemic burdens and incentives in decision-making is a general feature of surrogate decision-making. After establishing the claim, we draw out some of the implications for surrogate decision-making in medicine and offer philosophical and psychological explanations of the phenomenon. (shrink)

The puzzle of petitionary prayer: if we ask for the best thing, God was already going to do it, and if we ask for something that's not the best, God's not going to grant our request. In this paper, we give a new solution to the puzzle.

In biomedical ethics, there is widespread acceptance of moral realism, the view that moral claims express a proposition and that at least some of these propositions are true. Biomedical ethics is also in the business of attributing moral obligations, such as “S should do X.” The problem, as we argue, is that against the background of moral realism, most of these attributions are erroneous or inaccurate. The typical obligation attribution issued by a biomedical ethicist fails to truly capture the person's (...) actual obligations. We offer a novel argument for rife error in obligation attribution. The argument starts with the idea of an epistemic burden. Epistemic burdens are all of those epistemic obstacles one must surmount in order to achieve some aim. Epistemic burdens shape decision-making such that given two otherwise equal options, a person will choose the option that has the lesser of epistemic burdens. Epistemic burdens determine one's potential obligations and, conversely, their non-obligations. The problem for biomedical ethics is that ethicists have little to no access to others' epistemic burdens. Given this lack of access and the fact that epistemic burdens determine potential obligations, biomedical ethicists often can only attribute accurate obligations out of luck. This suggests that the practice of attributing obligations in biomedical ethics is rife with error. To resolve this widespread error, we argue that this practice should be abolished from the discourse of biomedical ethics. (shrink)

We thank all the thoughtful authors for their insightful comments. In this response, we try to address some of themes that emerged from the commentaries. We leave aside some of those comments that...

Various thinkers are concerned that the Orthodox view of Ancestral Sin does not avoid the age-old Augustinian concern of Pelagianism. After all, the doctrine of Ancestral Sin maintains that fallen human beings do not necessarily or inevitably commit actual sins. In contemporary literature, this claim could be articulated as a denial of the ‘inevitability thesis.’ A denial of the inevitability thesis, so contemporary thinkers maintain, seems to imply both that human beings can place themselves in right relation to God as (...) well as the Pelagian denial that all require Christ's work to attain this right relation to God. This article demonstrates that the Ancestral Sin, along with a denial of the inevitability thesis, is neither Pelagian nor Semi-Pelagian. I show that the doctrine of Ancestral Sin denies (Semi-) Pelagianism in various ways. I show that, for Ancestral Sin to entail (Semi-) Pelagianism, one must commit to several assumptions, each of which is plausibly deniable and none of which Orthodox thinkers affirm. (shrink)

Berger (forthcoming) states that moral intimacy is important in applying the best interests standard. But what he calls moral intimacy requires that someone has overcome epistemic burdens needed to represent the patient. We argue elsewhere that good surrogate decision-making is first and foremost a matter of overcoming epistemic burdens, or those obstacles that stand in the way of a surrogate decision-maker knowing what a patient wants and how to satisfy those preferences. Berger’s notion of moral intimacy depends on epistemic intimacy: (...) the fact that a surrogate's epistemic burdens with respect to the best interests of the incapacitated patient have been adequately surmounted, plus some other feature. Thus, where a particular patient-surrogate relationship fails to be morally intimate, what is lacking is either epistemic intimacy or this second feature. Furthermore, Berger uses the notion of moral intimacy as an explanans for the application of the best interests standard. We argue that the notions of epistemic intimacy and epistemic burdens not only help to explain the notion of moral intimacy, but also better explain the application of the best interests standard. Given the role of epistemic burdens and the epistemic intimacy that overcoming them enables, bioethicists and physicians should consider a surrogate’s epistemic standing relative to the patient’s best interests before pronouncing on the former’s ethical probity. (shrink)

We have now mapped the set of analogies Ai,j to conceptual and mechanical meanings. This allows us to recognize how the Group Algebraic System G decomposes into five smaller subsystems, each of which relate to well-known symbolic systems. Furthermore, by recognizing the algorithmic transformations between these subsystems, we can apply each representing a single component of the Group Algebraic System G, or model how algorithms are used in mathematics, by mapping its meaning onto the corresponding transformation steps between the subsystems. (...) Thus, we have transformed a Group Algebraic System G into five simpler subsystems (namely, symbolic analogic, lateral algebraic, calculus of infinity tensors, perturbations in waves, and algorithmic formation of symbols), each of which may also be represented algorithmically. This mapping process serves as a the basis for studying the algebraic machinery used in mathematics and logic to manipulate symbols, such as the classical logical systems or algebraic systems, using algorithms. (shrink)

Most current dental ethics curricula use a deontological approach to biomedical and dental ethics that emphasizes adherence to duties and principles as properties that determine whether an act is ethical. But the actual ethical orientation of students is typically unknown. The purpose of the current study was to determine the ethical orientation of dental students in resolving clinical ethical dilemmas. First-year students from one school were invited to participate in an electronic survey that included eight vignettes featuring ethical conflicts common (...) to the health care setting. The Multidimensional Ethics Scale was used to evaluate the students’ ethical judgments of these conflicts. Students rated each vignette along 13 ethically relevant items using a 7-point scale. Nine of the thirteen items were analyzed because they represent the dominant ethical theories, including deontology. One hundred sixteen dental students successfully completed the survey. Of the analyzed items, those associated with deontology had comparatively weak associations with whether students judged the action to be ethical and whether students judged themselves likely to perform the action. Whether an action was judged to be caring had the strongest association with whether the action was judged to be ethical and whether students judged themselves likely to perform the action. These results suggest that adherence to duties or principles has weaker association with students’ ethical judgments and behavior compared to caring, which was found to be more influential in their ethical judgments and behavior. Current dental school curricula with a primary focus on deontology may no. (shrink)

Healthcare systems need to consider not only how to prevent error, but how to respond to errors when they occur. In the United Kingdom’s National Health Service, one strand of this latter response is the ‘No Blame Culture’, which draws attention from individuals and towards systems in the process of understanding an error. Defences of the No Blame Culture typically fail to distinguish between blaming someone and holding them responsible. This article argues for a ‘responsibility culture’, where healthcare professionals are (...) held responsible in cases of foreseeable and avoidable errors. We demonstrate how healthcare professionals can justifiably be held responsible for their errors even though they work in challenging circumstances. We then review the idea of ‘responsibility without blame’, applying this to cases of error in healthcare. Sensitive to the undesirable effects of blaming healthcare professionals and to the moral significance of holding individuals accountable, we argue that a responsibility culture has significant advantages over a No Blame Culture due to its capacity to enhance patient safety and support medical professionals in learning from their mistakes, while also recognising and validating the legitimate sense of responsibility that many medical professionals feel following avoidable error, and motivating medical professionals to report errors. (shrink)

In a recent issue of Bioethics, I argued that compulsory moral bioenhancement should be administered covertly. Alexander Zambrano has criticized this argument on two fronts. First, contrary to my claim, Zambrano claims that the prevention of ultimate harm by covert moral bioenhancement fails to meet conditions for permissible liberty‐restricting public health interventions. Second, contrary to my claim, Zambrano claims that covert moral bioenhancement undermines autonomy to a greater degree than does overt moral bioenhancement. In this paper, I rebut both of (...) these arguments, then finish by noting important avenues of research that Zambrano’s arguments motivate. (shrink)

In this paper, we explore the properties and optimization techniques related to polyhedral cones and energy numbers with a focus on the cone of positive semidefinite matrices and efficient computation strategies for kernels. In Part (a), we examine the polyhedral nature of the cone of positive semidefinite matrices, , establishing that it does not form a polyhedral cone for due to its infinite dimensional characteristics. In Part (b), we present an algorithm for efficiently computing the kernel function on-the-fly, leveraging a (...) polyhedral description of the convex hull generated by the feature mappings and . By restructuring the problem and using gradient-based optimization techniques, our approach minimizes memory usage and computational overhead, thus enabling scalable computation. Through examples and visualizations, we demonstrate the practical applications and efficiency of the proposed algorithm in optimizing these kernel computations. (shrink)

Body dissatisfaction has long been considered an integral component of and driving force behind anorexia nervosa. In this paper, I characterise body dissatisfaction in terms of problematic beliefs about body size and the value of thinness. I suggest two methods for understanding these beliefs. Regarding body size beliefs, I suggest focusing on certain forms of misleading phenomenal evidence that sufferers of anorexia nervosa are exposed to. Regarding beliefs about the value of thinness, I suggest focusing on the benefits of such (...) beliefs. (shrink)

The collapse of society is inevitable, even if it is in the distant future. When it collapses, it is likely to do so within the lifetimes of some people. These people will have matured in pre-collapse society, experience collapse, and then live the remainder of their lives in the post-collapse world. I argue that this group of people—the transitional generation—will be the worst off from societal collapse, far worse than subsequent generations. As the transitional generation, they will suffer disparately. This (...) intergenerational disparity in suffering is inequitable. Given that other disparities in suffering are worthy of remediation, this intergenerational disparity in suffering is worthy of remediation. However, the only way to do so is to target the mental states of the members of the transitional generation. (shrink)

It has recently been argued that a person’s moral judgments (about both their own and others’ actions) are constrained by the nature and extent of their relevant ignorance and, thus, that such judgments are determined in the first instance by the person’s epistemic circumstances. It has been argued, in other words, that the epistemic is logically prior to other normative (e.g., ethical, prudential, pecuniary) considerations in human decision-making, that these other normative considerations figure in decision-making only after (logically and temporally) (...) relevant ignorance has constrained the decision-maker’s menu of options. If this is right, then a person’s moral judgments in some set of circumstances should vary with their knowledge and ignorance of these circumstances. In this study, we test the hypothesis of the logical priority of the epistemic. We describe two experiments in which subjects’ knowledge and ignorance of relevant consequences were manipulated. In the second experiment, we also compared the effect of ignorance on moral judgments with that of personal force, a factor previously shown to influence moral judgments. We found broad empirical support for the armchair arguments that epistemic considerations are logically prior to normative considerations. (shrink)

We present a novel approach to defining the mathematical constant π through the infinite den- sification of a sweeping net, which approximates a circle as the net becomes infinitely dense. By developing and enhancing notation related to sweeping nets and saddle maps, we establish a rigor- ous framework for expressing π in terms of the densification process using reverse integration. This method, inspired by the concept that numbers ”come from infinity,” leverages a reverse integral approach to model the transition from (...) infinite densification to the finite circle. Our work not only offers a new perspective on the geometric interpretation of π but also provides insights into reverse integration techniques and their applications in mathematical analysis. (shrink)

If you have enjoyed any of the 7 (seven) other books I have published over 20 years, including literally thousands of pages of mathematical and topological concepts, Python programs and conceptually expanding papers, please consider buying this book for $20.00 on google play books. -/- Introduction: -/- Though the following pages provide extensive exposition and dedicated descriptions of the phenomenological velocity formulas, theory and mystery, I thought it appropriate to write this introduction as a partial explanation for what phenomenal velocity (...) is, and describe, briefly its theory and applications. Phenomenological Velocity is a method for solving for something that ought cancel out with itself, but there are specific implicit forms for this thing that, “ought cancel out with itself,” namely the Lorentz coefficient ought cancel out with itself when applied to the height of a cone derived from the difference between the circumferences of two circles applied to the Pythagorean Theorem, or, more generally, the height implied by application of the Pythagorean theorem to the difference between two arc lengths’ equaling a third arc length. These difference equations are essential to conceptualizing differentiation, and in these further chapters, I demonstrate that the phenomenological velocity is, indeed the conditional derivative in the chapter, “Conditional Integral of Phenomenological Velocity.” The phenomenological velocity algebraic solution to the velocity within the Lorentz coefficient when applied to the height function in such a way that it ought cancel out with itself is both constructive mathematics and it employs the concept of, “bracketing,” - first introduced by Edmund Husserl in his writings on the phenomenological reduction. Phenomenological Velocity’s algebraic solution from the difference between two arc lengths applied to the Pythagorean Theorem to solve for a theoretical height (which is a projected distance in space), employs bracketing, because we, “set aside,” the existence of an undefined solution, namely due to the presence of necessitated complex analytical forms by the architecture of the equation, or the “mathetecture,” of the algebraic form. -/- With respect to theology, the phenomenological velocity is somehow symbolic of the creation itself; symbolic of creation due to the fact that we find the canceling out of the Lorentz coefficient as, “impotent,” non-existent or non-effecting to the mathetecture of the height function. However, via the modus-ponens work around to phenomenological velocity, which in itself does not require the complex field, but embeds implied complex field solutions to the equation while maintaining logical consistency, we find existence from non-existence. This is directly linguistically applicable to the concept of the big-bang, the resurrection of Yeshua the Messiah, and opens analogies for us to draw relationships between the, “fall,” of Adam and Eve as the generation of error, or the introduction of paradox, as we see the phallus representing paradox topologically. -/- The phenomenological velocity is a gestalt concept, relevant to cosmology, because we find that it is the perfect language-form for discussing dark matter. It does, however, require the reader to re-conceive or re-frame rather, some of the fundamental aspects of assumed physical reality like time, experience, solidity of dark matter, etc. We find the hidden dimension of phenomenological velocity to have been an overlooked aspect of mathematical physics by the researchers of Bell’s theorem and undoubtedly a host of other theorems. Thus, raising awareness about the real existence and necessitated reality of phenomenological velocity is in no way an endeavor deserving further procrastination by the scientific community, for doing so would be intellectually dishonest and further the propagation of incomplete or misleading theories on reality. -/- This work details how the Lorentz coefficient, when applied to the height of a cone in such a way as to cancel out with itself, permits the velocity variable to have a solution to it anyway, even though it ought cancel out with itself. This mathe-tecture, so to speak has consequences for complex analysis, and pave the way for, "transcendental relativity," building an adaptive framework for consciousness and physical reality. (shrink)

Description In this paper, we propose an advanced mathematical framework centered around the Energy Number Field (E), which fundamentally avoids the conventional concept of zero by introducing a neutral ele- ment, νE. Through this approach, we redefine core mathematical constructs, including limits, continuity, differentiation, integration, and series summation, ensuring they operate seamlessly within a zero-less paradigm. We address and redefine matrix operations, topology, metric spaces, and complex analysis, aligning them with the principles of E. Additionally, we explore non-mappable properties of (...) energy numbers in the context of symmetry groups, non-standard fields, fractional calculus, and non-Euclidean geometries. By employing νE as the central element, our framework resolves conventional zero-related sin- gularities and computational anomalies, offering a novel perspective that bridges advanced mathematical theories with practical applications in physics, computational algorithms, and topological transforma- tions. This work paves the way for future research to experimentally validate these formulations and explore potential applications in advanced physics, quantum mechanics, and beyond. (shrink)

In standard probability theory, probability zero is not the same as impossibility. But many have suggested that only impossible events should have probability zero. This can be arranged if we allow infinitesimal probabilities, but infinitesimals do not solve all of the problems. We will see that regular probabilities are not invariant over rigid transformations, even for simple, bounded, countable, constructive, and disjoint sets. Hence, regular chances cannot be determined by space-time invariant physical laws, and regular credences cannot satisfy seemingly reasonable (...) symmetry principles. Moreover, the examples here are immune to the objections against Williamson’s infinite coin flips. (shrink)

Published with great thanksgiving for Yaohushua, the living One Yahowah, "Jesus Christ." -/- In previous work, Formalizing Mechanical Analysis Using Sweeping Net Methods I, sweeping net methods have been extended to complex analysis, relying on the argument of complex functions defined on the unit circle. In this paper, we reformulate these methods purely within a real-valued and geometric framework, avoiding the use of complex analysis. By redefining the sweeping net constructs and the associated theorems using real functions and geometric interpretations (...) on the unit circle, we demonstrate how singularities and their approximations can be effectively analyzed without the need for imaginary numbers. This approach provides intuitive geometric insights and broadens the applicability of sweeping net methods in mathematical analysis. (shrink)

In this paper I’ll examine whether we could be justified in attributing consciousness to artificial intelligent systems. First, I’ll give a brief history of the concept of artificial intelligence (AI) and get clear on the terms I’ll be using. Second, I’ll briefly review the kinds of AI programs on offer today, identifying which research program I think provides the best candidate for machine consciousness. Lastly, I’ll consider the three most plausible ways of knowing whether a machine is conscious: (1) an (...) AI demonstrates a sufficient level of organizational similarity to that of a human thinker, (2) an inference to the best explanation, and (3) what I call “punting to panpsychism”, i.e., the idea that if everything is conscious, then we get machine consciousness in AI for free. However, I argue that all three of these methods for attributing machine consciousness are inadequate since they each face serious philosophical problems which I will survey and specifically tailor to each method. (shrink)

Schopenhauer’s pessimistic philosophy is a depressing read. He writes many pages about how suffering is the norm, and any happiness we feel is merely a temporary alleviation of suffering. Even so, his account of suffering rings true to many readers. What are we to do with our lives if Schopenhauer is right, and we are doomed to suffer? In this paper, I use William James’ pragmatic method to find practical implications of Schopenhauer’s pessimism. I provide a model for how we (...) are to live our lives in a suffering world, a model that provides means to reduce suffering. (shrink)

Stephen Davies taught philosophy at the University of Auckland, Auckland, New Zealand. His research specialty is the philosophy of art. He is a former President of the American Society for Aesthetics. His books include Definitions of Art (Cornell UP, 1991), Musical Meaning and Expression (Cornell UP, 1994), Musical Works and Performances (Clarendon, 2001), Themes in the Philosophy of Music (OUP, 2003), Philosophical Perspectives on Art (OUP, 2007), Musical Understandings and Other Essays on the Philosophy of Music (OUP, 2011), The (...) Artful Species: Aesthetics, Art, and Evolution (OUP, 2012), The Philosophy of Art (Wiley-Blackwell, 2016 second ed.), and Adornment: What Self-decorations Tells Us about Who We Are, (Bloomsbury Academic, 2020). (shrink)

[Stephen Yablo] The usual charge against Carnap's internal/external distinction is one of 'guilt by association with analytic/synthetic'. But it can be freed of this association, to become the distinction between statements made within make-believe games and those made outside them-or, rather, a special case of it with some claim to be called the metaphorical/literal distinction. Not even Quine considers figurative speech committal, so this turns the tables somewhat. To determine our ontological commitments, we have to ferret out all traces (...) of nonliterality in our assertions; if there is no sensible project of doing that, there is no sensible project of Quinean ontology. /// [Andre Gallois] I discuss Steve Yablo's defence of Carnap's distinction between internal and external questions. In the first section I set out what I take that distinction, as Carnap draws it, to be, and spell out a central motivation Carnap has for invoking it. In the second section I endorse, and augment, Yablo's response to Quine's arguments against Carnap. In the third section I say why Carnap's application of the distinction between internal and external questions runs into trouble. In the fourth section I spell out what I take to be Yablo's version of Carnap. In the last I say why that version is especially vulnerable to the objection raised in the second. (shrink)

We apply the analysis that we have developed over the course of several publications on the significance of ignorance for decision-making, especially in surrogate (and, thus, in political) contexts, to political decision-making, such as it has been, during the COVID-19 pandemic (see Scheall 2019; Crutchfield and Scheall 2019; Scheall and Crutchfield 2020; Scheall 2020). Policy responses to the coronavirus constitute a case study of the problem of policymaker ignorance. We argue that political responses to the virus cannot be explained by (...) assuming that the interests of policymakers were at loggerheads with those of their constituents at the beginning of the crisis. In order to explain the responses of policymakers, it is necessary to recognize the effects of relevant ignorance on their incentives to pursue different policy objectives. We discuss the knowledge that policymakers required at the start of the pandemic in order to deliberately realize the goal of limiting overall human suffering and the spontaneous forces that could have facilitated the realization of this goal. The problem of policymaker ignorance implies that policymakers have not earnestly pursued the goal of limiting overall suffering due to the novel coronavirus, but have repeatedly resorted to the pursuit of relatively less epistemically burdensome goals. The problem of policymaker ignorance explains why policymakers have focused primarily on limiting one kind of suffering – physical suffering due to the virus – and have mostly ignored related kinds of suffering, i.e., the economic, sociological, psychological, and physical suffering caused by policies to limit physical suffering from the virus. The problem of policymaker ignorance also helps to explain why policymakers relied on the relatively blunt instrument of economic lockdown rather than more focused protection policies, and why they continue to resort to lockdowns, despite the emerging scientific evidence of their ineffectiveness at mitigating physical suffering due to the virus. (shrink)

Brummett and Salter propose a useful and timely taxonomy of clinical ethics expertise (2019). As the field becomes further “professionalized” this taxonomy is important, and the core of it is right. It needs some refinement around the edges, however. In their conclusion, Brummett and Salter rightly point out that there is a significant difference between the ethicist whose recommendations are procedure- and process-heavy, consensus-driven, and dialogical and the authoritarian ethicist whose recommendations flow from “private moral views” (Brummett and Salter, 2019). (...) This admission doesn’t go far enough. Brummett and Salter’s taxonomy fails to capture the notion that offering recommendations whose normative force is moral is different in kind from recommendations whose normative force is non-moral, such as those recommendations that are free of moral content or justified by convention. The difference is in kind, not scale. I argue further that clinical ethics expertise, if possible, consists at least in offering recommendations whose normative force is moral. These two claims imply that the taxonomy fails to cut clinical ethics expertise at the joints: the ethicist who offers justified non-moral normative recommendations is a different kind of ethicist from the one who offers justified moral normative recommendations, yet both are categorized as clinical ethics experts. I finish by offering a refinement of the taxonomy that more precisely categorizes clinical ethicists. (shrink)