Rethinking the issue of reparations for Black Americans.

The differential impact of the COVID-19 pandemic on communities of color in the United States along with the civil unrest taking place in 2020 in response to the killing of unarmed Black men and women by the police have increased awareness of the structural racism pervading US society. These developments have reraised the issue of reparations for Black Americans, usually proposed in the context of providing financial compensation for the injustices of slavery to the descendants of those who were enslaved. This paper will discuss the systematic racial inequality and structural racism in US society that have significantly disadvantaged racial and ethnic minorities while giving advantages to white Americans, which most recently have resulted in significantly higher mortality and morbidity among Black, Hispanic, and Native Americans during the pandemic. The paper will conceptualize reparations within the context of theories of reparative justice. It will also consider whether reparations are owed, and if so, by whom, to whom, and in what form. The final section will offer a proposal for collective reparations to the Black community and other people of color.

Do Pluripotent Stem Cells Offer a New Path to Reproduction?

The ability of pluripotent stem to develop into any of the cell types in the human body has meant that it was only a matter of time before scientists would try to transform them into human gametes. Up to now though it has not been possible to do so. Nevertheless a 2016 book written by Henry Greely speculated that in twenty to forty years most people in developed countries will cease reproduction through sex, using sex exclusively for pleasure, and instead will rely on reproduction through pluripotent stem cell-derived gametes. This paper will offer a different perspective. After describing the process through which human pluripotent stem cells might eventually be coaxed into gametes, it will show why the use of pluripotent stem cell-derived gametes for reproductive purposes would present significant safety, ethical, and regulatory challenges.

The nuclear bile acid receptor FXR is a PKA- and FOXA2-sensitive activator of fasting hepatic gluconeogenesis.

BACKGROUND & AIMS: Embedded into a complex signaling network that coordinates glucose uptake, usage and production, the nuclear bile acid receptor FXR is expressed in several glucose-processing organs including the liver. Hepatic gluconeogenesis is controlled through allosteric regulation of gluconeogenic enzymes and by glucagon/cAMP-dependent transcriptional regulatory pathways. We aimed to elucidate the role of FXR in the regulation of fasting hepatic gluconeogenesis. METHODS: The role of FXR in hepatic gluconeogenesis was assessed in vivo and in mouse primary hepatocytes. Gene expression patterns in response to glucagon and FXR agonists were characterized by quantitative reverse transcription PCR and microarray analysis. FXR phosphorylation by protein kinase A was determined by mass spectrometry. The interaction of FOXA2 with FXR was identified by cistromic approaches and in vitro protein-protein interaction assays. The functional impact of the crosstalk between FXR, the PKA and FOXA2 signaling pathways was assessed by site-directed mutagenesis, transactivation assays and restoration of FXR expression in FXR-deficient hepatocytes in which gene expression and glucose production were assessed. RESULTS: FXR positively regulates hepatic glucose production through two regulatory arms, the first one involving protein kinase A-mediated phosphorylation of FXR, which allowed for the synergistic activation of gluconeogenic genes by glucagon, agonist-activated FXR and CREB. The second arm involves the inhibition of FXR's ability to induce the anti-gluconeogenic nuclear receptor SHP by the glucagon-activated FOXA2 transcription factor, which physically interacts with FXR. Additionally, knockdown of Foxa2 did not alter glucagon-induced and FXR agonist enhanced expression of gluconeogenic genes, suggesting that the PKA and FOXA2 pathways regulate distinct subsets of FXR responsive genes. CONCLUSIONS: Thus, hepatic glucose production is regulated during physiological fasting by FXR, which integrates the glucagon/cAMP signal and the FOXA2 signal, by being post-translationally modified, and by engaging in protein-protein interactions, respectively. LAY SUMMARY: Activation of the nuclear bile acid receptor FXR regulates gene expression networks, controlling lipid, cholesterol and glucose metabolism, which are mostly effective after eating. Whether FXR exerts critical functions during fasting is unknown. The results of this study show that FXR transcriptional activity is regulated by the glucagon/protein kinase A and the FOXA2 signaling pathways, which act on FXR through phosphorylation and protein-protein interactions, respectively, to increase hepatic glucose synthesis.

Ethical Guidelines for Genetic Research on Alcohol Addiction and Its Applications.

Research on the genomic correlates to addiction raises ethical issues in a number of different domains. In this paper, we evaluate the status of genetic research on alcohol dependence as background to addressing the ethical issues raised in conducting research on addiction and the application of that research to the formulation of public policies. We conclude that genetic testing is not yet ready for use in the prediction of alcohol dependence liability. Pharmacogenetic testing for responses to treatments may have more clinical utility, although additional research is required to demonstrate utility and cost-effectiveness. Genetic research on addiction raises potential risks for participants that must be clearly communicated to participants, including limitations on the ability of researchers to protect their privacy. Responsible communication of research findings is essential to prevent common misunderstandings about the role of genetics in addiction liability, to prevent its premature or inappropriate use, and to reduce discrimination and stigmatization experienced by addicted individuals. More research is needed to determine the impact of genetic explanations on addicted individuals, treatment-seeking behavior, and on public attitudes towards addicted persons. Importantly, genetic research on addiction must not be at the expense of investments in social, behavioral, and psychological research on addiction.

Ethical and practical challenges in providing noninvasive prenatal testing for chromosome abnormalities: an update.

PURPOSE OF REVIEW: Noninvasive prenatal testing (NIPT) through the analysis of cell-free DNA in maternal plasma has rapidly changed screening for fetal chromosome abnormalities. We review practical and ethical challenges associated with the transition, progress in their resolution, and identify new emerging difficulties. RECENT FINDINGS: NIPT is an advanced screening test for trisomies 21, 18, and 13 that was initially limited to women at high risk for an affected pregnancy. It is now recognized as suitable for all women. The testing has been expanded to include sex chromosome abnormalities and some microdeletion syndromes. Some ethicists are concerned about inclusion of disorders that have less severe phenotypes. SUMMARY: Clinical providers have experienced difficulty in maintaining an up-to-date knowledge about the scope of NIPT, differences between tests, who should be offered the testing, performance of tests, reasons for false-positive results, and optimal patient management following positive results. Some of the practical difficulties associated with the introduction can be attributed to this knowledge gap. There remain some important ethical issues associated with NIPT. We believe that the same ethical and legal principles that were considered in the justification of conventional prenatal screening can be used to assess the appropriateness of additional NIPT applications.

Assessing the universal health coverage target in the Sustainable Development Goals from a human rights perspective.

BACKGROUND: The UN's Sustainable Development Goals (SDGs), adopted in September 2015, include a comprehensive health goal, "to ensure healthy lives and promote well-being at all ages." The health goal (SDG 3) has nine substantive targets and four additional targets which are identified as a means of implementation. One of these commitments, to achieve universal health coverage (UHC), has been acknowledged as central to the achievement of all of the other health targets. As defined in the SDGs, UHC includes financial risk protection, access to quality essential health-care services, and access to safe, effective, quality and affordable essential medicines and vaccines for all. DISCUSSION: This article evaluates the extent to which the UHC target in the SDGs conforms with the requirements of the right to health enumerated in the International Covenant on Economic, Social and Cultural Rights, the Convention on the Rights of the Child, and other international human rights instruments and interpreted by international human rights bodies. It does so as a means to identify strengths and weaknesses in the framing of the UHC target that are likely to affect its implementation. While UHC as defined in the SDGs overlaps with human rights standards, there are important human rights omissions that will likely weaken the implementation and reduce the potential benefits of the UHC target. The most important of these is the failure to confer priority to providing access to health services to poor and disadvantaged communities in the process of expanding health coverage and in determining which health services to provide. Unless the furthest behind are given priority and strategies adopted to secure their participation in the development of national health plans, the SDGs, like the MDGs, are likely to leave the most disadvantaged and vulnerable communities behind.

From conceptual pluralism to practical agreement on policy: global responsibility for global health.

BACKGROUND: As the human cost of the global economic crisis becomes apparent the ongoing discussions surrounding the post-2015 global development framework continue at a frenzied pace. Given the scale and scope of increased globalization moving forward in a post-Millennium Development Goals era, to protect and realize health equity for all people, has never been more challenging or more important. The unprecedented nature of global interdependence underscores the importance of proposing policy solutions that advance realizing global responsibility for global health. DISCUSSION: This article argues for advancing global responsibility for global health through the creation of a Global Fund for Health. It suggests harnessing the power of the exceptional response to the combined epidemics of AIDS, TB and Malaria, embodied in the Global Fund to Fight AIDS, Tuberculosis and Malaria, to realize an expanded, reconceptualized Global Fund for Health. However this proposal creates both an analytical quandary embedded in conceptual pluralism and a practical dilemma for the scope and raison d'etre of a new Global Fund for Health. To address these issues we offer a logical framework for moving from conceptual pluralism in the theories supporting global responsibility for health to practical agreement on policy to realize this end. We examine how the innovations flowing from this exceptional response can be coupled with recent ideas and concepts, for example a global social protection floor, a Global Health Constitution or a Framework Convention for Global Health, that share the global responsibility logic that underpins a Global Fund for Health. CONCLUSIONS: The 2014 Lancet Commission on Global Governance for Health Report asks whether a single global health protection fund would be better for global health than the current patchwork of global and national social transfers. We concur with this suggestion and argue that there is much room for practical agreement on a Global Fund for Health that moves from the conceptual level into policies and practice that advance global health. The issues of shared responsibility and mutual accountability feature widely in the post-2015 discussions and need to be addressed in a coherent manner. Our article argues why and how a Global Fund for Health effectuates this, thus advancing global responsibility for global health.

Obstetricians and gynecologists' practice and opinions of expanded carrier testing and noninvasive prenatal testing.

OBJECTIVE: The objective of this study is to assess the opinions of Fellows of the American College of Obstetricians and Gynecologists on expanded carrier testing (molecular detection of >100 genetic diseases of variable severity) and noninvasive prenatal testing (NIPT). METHODS: A survey conducted between March and August 2012, assessed current use of testing, provision of genetic counseling, types of disorders that should be identified, preferences for future use, ethical aspects, and views on regulatory oversight. RESULTS: Expanded carrier testing was offered to all patients by 15% of the responders and 52.1% upon patient request. Most (67.3%) favored testing only for mutations of known significance. In this study, 79.1% supported the use of NIPT as a screen for Down syndrome for all women with 47.9% viewing NIPT as a complete substitution for invasive testing. Most supported expansion to other aneuploidies (97.5%) and severe early-onset Mendelian disorders (90.4%) but not for adult-onset disorders (29.8%) or nonmedical sex identification (15.7%). A majority (73.2%) believed that NIPT would increase pregnancy terminations for mild disease states. Respondents favored a role for professional societies in providing regulatory oversight. CONCLUSION: Rapid incorporation of new genetic technologies may be limited by the availability of genetic counseling, concerns regarding inclusion of clinically mild disorders, results of unknown significance, and costs.

Noninvasive prenatal testing for early sex identification: a few benefits and many concerns.

A new technology, noninvasive prenatal testing (NIPT), can identify fetal sex early in pregnancy, five weeks after conception, with a high degree of accuracy through analysis of maternal blood plasma. This article considers the possibility that NIPT will encourage greater sex selection in developed countries and discusses the implications. Sex selection raises serious social and ethical issues unless it is done for medical reasons. The article also assesses options to discourage sex-selective abortions, including the effectiveness of potential legal measures.

What could a strengthened right to health bring to the post-2015 health development agenda?: interrogating the role of the minimum core concept in advancing essential global health needs.

BACKGROUND: Global health institutions increasingly recognize that the right to health should guide the formulation of replacement goals for the Millennium Development Goals, which expire in 2015. However, the right to health's contribution is undercut by the principle of progressive realization, which links provision of health services to available resources, permitting states to deny even basic levels of health coverage domestically and allowing international assistance for health to remain entirely discretionary. DISCUSSION: To prevent progressive realization from undermining both domestic and international responsibilities towards health, international human rights law institutions developed the idea of non-derogable "minimum core" obligations to provide essential health services. While minimum core obligations have enjoyed some uptake in human rights practice and scholarship, their definition in international law fails to specify which health services should fall within their scope, or to specify wealthy country obligations to assist poorer countries. These definitional gaps undercut the capacity of minimum core obligations to protect essential health needs against inaction, austerity and illegitimate trade-offs in both domestic and global action. If the right to health is to effectively advance essential global health needs in these contexts, weaknesses within the minimum core concept must be resolved through innovative research on social, political and legal conceptualizations of essential health needs. SUMMARY: We believe that if the minimum core concept is strengthened in these ways, it will produce a more feasible and grounded conception of legally prioritized health needs that could assist in advancing health equity, including by providing a framework rooted in legal obligations to guide the formulation of new health development goals, providing a baseline of essential health services to be protected as a matter of right against governmental claims of scarcity and inadequate international assistance, and empowering civil society to claim fulfillment of their essential health needs from domestic and global decision-makers.

Promoting children's rights to health and well-being in the United States.

The United States has a highly sophisticated pediatric healthcare system and spends more than any other country per capita on children's healthcare. However, not all children have access to needed and affordable health care and the life expectancy and health outcomes of children in the country are worse than in any other industrialized nation. These nations typically offer universal healthcare for children as part of a robust recognition of a children's rights framework. In 1989 the United Nations adopted the Convention on the Rights of the Child that recognizes the right of the child to the highest attainable standard of health and to facilities for the treatment of illness and rehabilitation of health. Currently the United States is the only United Nations member country that has not ratified the Convention on the Rights of the Child. This paper outlines the potential benefits of adopting a child rights approach based on the principles and provisions of the Convention on the Rights of the Child. The fact that countries who invest much less in healthcare compared to the United States can achieve better health outcomes provides the certainty that a solution is possible and within reach.

Genetic aspects of adrenocortical tumours and hyperplasias.

Adrenocortical tumours (ACT), which include adenomas, carcinomas and adrenal hyperplasia, may be associated with genetic syndromes, such as Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, multiple endocrine neoplasia type 1, familial adenomatous polyposis and Carney complex. Genetic defects have been found to be responsible for the disease in most of these syndromes, allowing genetic counselling to affected patients and family members. Here, we summarize the clinical criteria of these hereditary syndromes and briefly describe the genetic alterations related to them. In addition, we discuss the involvement of various genetic defects in the development of sporadic adrenocortical tumours.

Evaluating the first-in-human clinical trial of a human embryonic stem cell-based therapy.

Phase I clinical trials generally raise greater ethical and human protection challenges than later stage clinical trials, suggesting a need to proceed cautiously. This is particularly the case for Phase I trials with a novel therapy being tested in humans for the first time, usually termed first-in-human (FIH) trials. In January 2009, the Food and Drug Administration approved the Investigational New Drug application of Geron Corporation, a small California-based biopharmaceutical company, to initiate a clinical trial to assess GRNOPC1, a human embryonic stem cell-derived candidate therapy for severe spinal cord injuries. This article evaluates the ethical and human subject protection issues raised by the Geron FIH trial. It identifies problems with the approval process and with the conduct of the trial, and then recommends ways to improve review of future proposed trials with novel and high-risk therapies.

Distortions of sex ratios at birth in the United States; evidence for prenatal gender selection.

OBJECTIVE: The normal male to female livebirth sex ratio ranges from 1.03 to 1.07. Higher ratios in China, India and Korea reflect prenatal sex selection. We reviewed sex ratios for US births to investigate potential prenatal sex selection. METHODS: We reviewed all US livebirths from 1975 to 2002 using National Center for Health Statistics birth certificates in 4-year intervals. We compared the sex ratios of Blacks, Chinese, Filipinos, Asian Indians and Koreans relative to Whites. We also compared the sex ratios by birth order for first, second and third and more births (third+) from 1991 to 2002. RESULTS: The male to female sex ratio from 1975 to 2002 was 1.053 for Whites, 1.030 (p < 0.01) for Blacks, 1.074 (p < 0.01) for Chinese and 1.073 (p < 0.01) for Filipinos. From 1991 to 2002, the sex ratio increased from 1.071 to 1.086 for Chinese, 1.060 to 1.074 for Filipinos, 1.043 to 1.087 for Asian Indians and 1.069 to 1.088 for Koreans. The highest sex ratios were seen for third+ births to Asian Indians (1.126), Chinese (1.111) and Koreans (1.109). CONCLUSION: The male to female livebirth sex ratio in the United States exceeded expected biological variation for third+ births to Chinese, Asian Indians and Koreans strongly suggesting prenatal sex selection.

Climate Justice, Humans Rights, and the Case for Reparations.

The global community is facing an existential crisis that threatens the web of life on this planet. Climate change, in addition to being a fundamental justice and ethical issue, constitutes a human rights challenge. It is a human rights challenge because it undermines the ability to promote human flourishing and welfare through the implementation of human rights, particularly the right to life and the right to health. It is also a human rights challenge because climate change disproportionately impacts poor and the vulnerable people in both low-income and high-income countries. Those living in many low-income countries are subject to the worst impacts of climate change even though they have contributed negligibly to the problem. Further, low-income countries have the fewest resources and capabilities at present to adapt or cope with the severe, long-lasting impacts of climate change. Building on human rights principles of accountability and redress for human rights violations, this paper responds to this injustice by seeking to make long-neglected societal amends through the implementation of the concept of climate reparations. After discussing the scientific evidence for climate change, its environmental and socioeconomic impacts, and the ethical and human rights justifications for climate reparations, the paper proposes the creation of a new global institutional mechanism, the Global Climate Reparations Fund, which would be linked with the United Nations Human Rights Council, to fund and take action on climate reparations. This paper also identifies which parties are most responsible for the current global climate crisis, both historically and currently, and should therefore fund the largest proportion of climate-related reparations.