Shortages of new therapeutics to treat coronavirus disease (COVID-19) have forced clinicians, public health officials, and health systems to grapple with difficult questions about how to fairly allocate potentially life-saving treatments when there are not enough for all patients in need (1). Shortages have occurred with remdesivir, tocilizumab, monoclonal antibodies, and the oral antiviral Paxlovid (2) -/- Ensuring equitable allocation is especially important in light of the disproportionate burden experienced during the COVID-19 pandemic by disadvantaged groups, including Black, Hispanic/Latino and (...) Indigenous communities, individuals with certain disabilities, and low-income persons. However, many health systems have resorted to first-come, first-served approaches to allocation, which tend to disadvantage individuals with barriers in access to care (3). There is mounting evidence of racial, ethnic, and socioeconomic disparities in access to medications for COVID-19 (4, 5). -/- One potential method to promote equitable allocation is to use a weighted lottery, which is an allocation strategy that gives all eligible patients a chance to receive the scarce treatment while also allowing the assignment of higher or lower chances according to other ethical considerations (6). We sought to assess the feasibility of implementing a weighted lottery to allocate scarce COVID-19 medications in a large U.S. health system and to determine whether the weighted lottery promotes equitable allocation. (shrink)

BackgroundIn the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies.MethodsBetween 2013 and 2019, 8252 participants (...) (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported.ResultsSevere structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy.ConclusionThe management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/nct02220582. (shrink)

We report the results of a randomized trial to assess the impact of an innovative ethics curriculum on the knowledge and confidence of 85 medical house officers in a university hospital programme, as well as their responses to a simulated clinical case. Twenty-five per cent of the house officers received a lecture series, 25 per cent received lectures and case conferences, with an ethicist in attendance, and 50 per cent served as controls. A post-intervention questionnaire was administered. Knowledge scores did (...) not differ among the groups. Confidence regarding ethical issues was significantly greater in the aggregate intervention group compared to the control group. Confidence regarding procedural issues related to ethics was significantly higher for the EI group than for the controls. Responses to a simulated case showed that significantly fewer house officers in the EI group would intubate a patient for whom such therapy would be futile. We conclude that ethics education can have an impact on house officers' confidence and their responses to a simulated case, and that the EI was more effective than the LI. Such results have implications regarding the implementation of ethics education during residency. (shrink)

"By combining recent advances in the physical sciences with some of the novel ideas, techniques, and data of modern biology, this book attempts to achieve a new and different kind of evolutionary synthesis. I found it to be challenging, fascinating, infuriating, and provocative, but certainly not dull."--James H, Brown, University of New Mexico "This book is unquestionably mandatory reading not only for every living biologist but for generations of biologists to come."--Jack P. Hailman, Animal Behaviour , review of the first (...) edition "An important contribution to modern evolutionary thinking. It fortifies the place of Evolutionary Theory among the other well-established natural laws."--R.Gessink, TAXON. (shrink)

Rita Bottino,1 Santosh Nagaraju,2 Vikas Satyananda,2 Hidetaka Hara,2 Martin Wijkstrom,2 Massimo Trucco,1 David KC Cooper2 1Institute of Cellular Therapeutics, Allegheny Health Network, 2Thomas E Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA: Diabetes mellitus is increasing worldwide. Type 1 diabetes can be treated successfully by islet allotransplantation, the results of which are steadily improving. However, the number of islets that can be obtained from deceased human donors will never be sufficient to cure more than a very (...) small percentage of patients who might benefit from transplantation. Although there are some differences in glucose metabolism between pigs and humans, the use of pigs could provide an unlimited supply of islets, and the insulin produced would undoubtedly control glucose levels. Transplantation of islets into the portal vein results in islets residing in the liver; however, an early inflammatory response and rejection remain problematic, even when the recipient is receiving immunosuppressive therapy. In the long term, immunosuppressive drugs may exhibit toxicities to patients and specifically harm the islet cells. In contrast, encapsulation techniques provide islets with a physical barrier that prevents antibodies binding to the islet graft while still allowing insulin to be released into the recipient's circulation; in theory, patients receiving encapsulated grafts might not require exogenous immunosuppressive therapy. Nonhuman primates with encapsulated pig islet transplants have remained insulin-independent for several weeks, but long-term efficacy remains uncertain. Furthermore, techniques are now available to knock out genes from the pig and/or insert human genes, thus rendering the antigenic structure of pigs closer to that of humans, and providing protection from the human immune response. Islet transplantation from genetically engineered pigs has been followed by insulin independence in a small number of nonhuman primates for greater than 1 year. Neonatal islets have some advantages over adult islets in that they are easier to isolate and culture, and have the ability to proliferate during the first few months after transplantation. In 2009, the International Xenotransplantation Association set up a group to encourage and advise on clinical trials of pig islet xenotransplantation; this group's guidelines are discussed. Clinical trials of encapsulated pig islets are already under way. Keywords: diabetes, islets, pancreatic, pig, xenotransplantation. (shrink)

Perforation or gap formation in a vegetation is a major process in landscape transformation. The occurrence of gaps profoundly alters the microclimatical conditions in a vegetation. A method is proposed to quantify perforation by using the three main 2-D characteristics of the gaps: area, number and boundary length. New measures are developed by normalizing the observed values to the reference status of minimum and maximum perforation. As minimum perforation status, the presence of one single gap with area equal to the (...) map resolution is assumed. The new measures are combined using a 3-D Euclidean distance to visualize the process and to detect changes. The method is exemplified using a field case of gaps in a tropical terra firme rainforest at Tiputini, Ecuador. (shrink)

A number of authors have drawn attention to the contributions to geology of Robert Hooke, and it has been pointed out that in several ways his ideas were more advanced than those of Steno, who is sometimes taken to be the founder of geology as a scientific discipline. Moreover, it has been argued that in a number of instances Hooke should receive the credit for ideas which are usually believed to have originated in the work of James Hutton. This recognition (...) of the significance of Hooke's work is regarded by the present writer as being well founded. But, by contrast, the relationship between Hooke's geological ideas and his views on the proper methods for conducting scientific enquiries has been largely overlooked, and his views on the methodology of science, as revealed in his Posthumous works, have received little discussion. Moreover, on one of the few occasions on which they were discussed, by William Whewell, they were belittled. Whewell regarded Hooke's methodological contribution as merely ‘an attempt to adapt the Novum organon to the age which succeeded its publication’, 5 and he implied that the ‘same imperfections’ were to be found in the writings of both Hooke and Bacon. The influence of Bacon is, to be sure, most obvious in Hooke's general philosophy. Nevertheless, it will be argued that Hooke had a much clearer idea than did Bacon of the importance of so-called ‘hypothetico-deductive’ methods in science, and that in many ways his methodological views represent a significant advance on those of Bacon. (shrink)

The Greeks attributed to Thales a great many discoveries and achievements. Few, if any, of these can be said to rest on thoroughly reliable testimony, most of them being the ascriptions of commentators and compilers who lived anything from 700 to 1,000 years after his death—a period of time equivalent to that between William the Conqueror and the present day. Inevitably there ilso accumulated round the name of Thales, as round that of Pythagoras , a number of anecdotes of varying (...) degrees of plausibility and of no historical worth whatsoever. These and the achievements credited to Thales have, of course, been painstakingly brought together by Hermann Diels in Der Fragmente der Vorsokratiker. Useful and necessary as this work undoubtedly is, it nevertheless has probably contributed as much as any other book to the exaggerated and false Aew of Thales which we meet in so many modern histories of science or philosophy, and which it is the purpose of this article to combat. (shrink)

The fifth poem in Horace's first book of Epistles takes the form of an invitation to Torquatus to attend a dinner which the poet is preparing for that evening, the eveof the Emperor's birthday. The fare will be simple but Horace will see to it that the furnishings, napkins, vessels and plates will be clean and bright and that the company and the seating-plan will be to Torquatus’ taste. Horace will get Butra and Septicius to be there, and Sabinus, too, (...) as long as he is not kept away by a prior dinner engagement or by a girl he'd rather spend the evening with. With Torquatus and Horace, that makes four or five diners, so that there is room for others before the triclinium is full, although there shouldn't be too many; or, as Horace puts it :locus est et pluribus umbris;sed nimis arta premunt olidae conuiuia caprae. (shrink)