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The article discusses the author's argument about welfare versus autonomy in human subject research in the U.S. It notes that autonomy should be compromised even further for the sake of the welfare of research subjects. The article also provides discussions on the values of autonomy and welfare, drug laws relative to the volunteering of people to be subjects of clinical trials, and informed consent.

In this article, I consider how the interpretation of today's Constitution should be affected by the antebellum Constitution's accommodation of slavery and by the limitation of the franchise, at the time of the antebellum Constitution, to a small minority of the adult population. I refer to these defects in the antebellum Constitution and the political system that produced it as "original exclusions." In view of these original exclusions, the mere ratification of provisions of the antebellum Constitution cannot imbue them with sufficient moral legitimacy to override contemporary statutes. Thus, a justification for originalism based on notions of popular sovereignty must fail. The original exclusions also straightforwardly defeat the argument that originalism achieves desirable results because the Constitution was produced under supermajoritarian voting rules. In fact, as the Constitution is so hard to amend, and as there has been moral progress since the time of the antebellum Constitution, it makes sense to assume that the original meaning of some remaining antebellum provisions is morally retrograde and undesirable. The progressive elimination of the original exclusions was accomplished, in part, through nonoriginalist means and has increased the moral legitimacy of the Constitution. As the moral legitimacy of the Constitution derives, in part, from past nonoriginalism, future nonoriginalism should require less justification. There are some cases in which the text or original meaning of a constitutional provision was plausibly affected by an original exclusion. There are also cases in which application of a constitutional provision specially affects a previously--excluded class. If one or both of these conditions apply, the originalist position becomes even weaker. Most fundamentally, originalism is objectionable because it seeks to fix the meaning of antebellum provisions in the legal and political culture that produced the original exclusions. [ABSTRACT FROM AUTHOR]

The article focuses on utilitarian perspective on humanitarian intervention. Humanitarian intervention is defined as use of force by a state, beyond its border, that has as a purpose or an effect the protection of human rights of noncitizens or the reduction of the suffering of noncitizens. Political organizations such as states care far more about the welfare of their own members than they care about the welfare of nonmembers. Another factor which limits humanitarian intervention is anti-intervention norms in international law and international politics.

Low serum levels of 25-hydroxyvitamin D [25(OH)D] and low sunlight exposure are known risk factors for the development of multiple sclerosis. Add-on vitamin D supplementation trials in established multiple sclerosis have been inconclusive. The effects of vitamin D supplementation to prevent multiple sclerosis is unknown. We aimed to test the hypothesis that oral vitamin D3 supplementation in high-risk clinically isolated syndrome (abnormal MRI, at least three T2 brain and/or spinal cord lesions), delays time to conversion to definite multiple sclerosis, that the therapeutic effect is dose-dependent, and that all doses are safe and well tolerated. We conducted a double-blind trial in Australia and New Zealand. Eligible participants were randomized 1:1:1:1 to placebo, 1000, 5000 or 10 000 international units (IU) of oral vitamin D3 daily within each study centre (n = 23) and followed for up to 48 weeks. Between 2013 and 2021, we enrolled 204 participants. Brain MRI scans were performed at baseline, 24 and 48 weeks. The main study outcome was conversion to clinically definite multiple sclerosis based on the 2010 McDonald criteria defined as either a clinical relapse or new brain MRI T2 lesion development. We included 199 cases in the intention-to-treat analysis based on assigned dose. Of these, 116 converted to multiple sclerosis by 48 weeks (58%). Compared to placebo, the hazard ratios (95% confidence interval) for conversion were 1000 IU 0.87 (0.50, 1.50); 5000 IU 1.37 (0.82, 2.29); and 10 000 IU 1.28 (0.76, 2.14). In an adjusted model including age, sex, latitude, study centre and baseline symptom number, clinically isolated syndrome onset site, presence of infratentorial lesions and use of steroids, the hazard ratios (versus placebo) were 1000 IU 0.80 (0.45, 1.44); 5000 IU 1.36 (0.78, 2.38); and 10 000 IU 1.07 (0.62, 1.85). Vitamin D3 supplementation was safe and well tolerated. We did not demonstrate reduction in multiple sclerosis disease activity by vitamin D3 supplementation after a high-risk clinically isolated syndrome., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objectives: The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, reduces human prostate cancer incidence, and similar GLP-1 receptor agonists reduce in vitro proliferation and in vivo growth of prostate cancer cell lines. Primary human prostate cancer expresses the GLP-1 receptor (GLP-1R) in vitro . Cancer evolves with stage, and whether advanced-stage human prostate cancer expresses GLP-1R is unknown. We hypothesised and aimed to prove that human metastatic castrate-resistant prostate cancer (mCRPC) expresses the GLP-1R in vivo . We hypothesised that mCRPC would thus be detectable by positron emission tomography/computed tomography (PET/CT) using a radiotracer bound to a GLP-1R ligand, as in exendin PET/CT., Materials and Methods: Men with mCRPC, with more than one prostate-specific membrane antigen (PSMA)-avid lesion on PET/CT scanning (pathognomic in that setting for prostate cancer lesions), were approached to undergo PET/CT with gallium 68 -Dota-exendin-4. We documented PET/CT PSMA-avid lesions, which were also PET/CT exendin avid, as evidence of in vivo GLP-1R expression., Results: Out of the 24 men referred, three did not meet the inclusion criteria. Seventeen declined, largely because the study offered them no therapeutic benefit. Among the four men imaged, three had no exendin-avid lesions, while one had six osseous PSMA-avid lesions, three of which were also exendin avid., Conclusions: We demonstrated in vivo GLP-1R expression by human mCPRC, detecting PET/CT lesions avid for both PSMA and exendin, in one of four participants. GLP-1R expression may thus occur even in advanced-stage prostate cancer. Our data contribute to growing evidence supporting the testing of GLP-1 receptor agonists for therapeutic benefit in prostate cancer., Competing Interests: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (© the author(s).)