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IntroductionEquipoise, generally defined as uncertainty about the relative effects of the treatments being compared in a trial, is frequently referenced as an ethical standard for the conduct of randomized clinical trials. However, it seems to be defined in several different ways and may be used differently by different individuals. We explored how clinical researchers, chairs of research ethics boards, and philosophers of science define and reason with this term.MethodsWe completed semi-structured interviews about clinical trial ethics with 15 clinical researchers, 15 research ethics board chairs, and 15 philosophers of science/bioethicists. Each participant was asked a standardized set of 10 questions, 4 of which were specifically about equipoise. All interviews were conducted telephonically and transcribed. Responses were grouped and analysed via a modified grounded theory method.ResultsForty-three respondents defined equipoise in 7 logically distinct ways, and 2 respondents could not explicitly define it. The most common definition, offered by 14 respondents (31%), defined "equipoise" as a disagreement at the level of a community of physicians. There was significant variability in definitions offered between and within groups. When asked how they would "operationalize" equipoise - i.e. check or test for its presence - respondents provided 7 alternatives, the most common being in relation to a literature review (15/45, 33%). The vast majority of respondents (35/45, 78%) felt the concept was helpful, though many acknowledged that the lack of a clear definition or operationalization was problematic.ConclusionThere is significant variation in definitions of equipoise offered by respondents, suggesting that parties within groups and between groups may be referring to different concepts when they reference "equipoise". This non-uniformity may impact fairness and transparency and opens the door to potential ethical problems in the evaluation of clinical trials - for in

Despite their broad distribution across the North Pacific Ocean, the only known spawning grounds for Pacific Bluefin Tuna (Thunnus orientalis) are around coastal Japan and the East China Sea. However, an increase in the prevalence of large bluefin tuna up to 10 years old in the California Current System during exceptionally warm ocean conditions has led to speculation that they may be spawning in this region. To investigate this possibility, we collected samples from 36 females (estimated 3-8 years old) between 2015 and 2019. Histological analyses revealed no signs of imminent, active, or recent spawning. Further examination of historical ichthyoplankton collections showed no records of larval bluefin tuna, but confirmed the presence of the larvae of other tuna species in waters > 24°C. Fishery-dependent records showed that bluefin tuna are rarely recorded in purse seine catches where surface temperatures exceed 23°C. Our study, therefore, provided no evidence of bluefin tuna reproduction in the CCS. However, more comprehensive sampling, in particular off southern Baja California, may be required to confirm the absence of spawning.

Over the last two decades, antidepressant prescribing in the UK has increased considerably. The rate of antidepressant prescribing increased from 15.8% to 16.6% between 2015 and 2018, with 7.3 million people prescribed antidepressants in 2017/18, at an annual cost of approximately £266 million. Evidence suggests that the increase in the number of antidepressant prescriptions is due to patients staying on treatment for longer. While between a third to a half of patients may no longer be clinically indicated to continue antidepressant treatment, some are prepared to do so due to a fear of relapse or withdrawal symptoms during the discontinuation process. This PhD aimed to explore beliefs, attitudes, and behavioural intentions towards long-term antidepressant use in the management of people with depression in primary care. A critical interpretive synthesis found that beliefs and attitudes towards depression and antidepressant use influenced patients’ decisions to stop or continue long-term antidepressant treatment. The findings from the synthesis were considered along with existing theoretical models of health behaviour to develop a questionnaire to measure patients’ beliefs, attitudes, and behavioural intentions towards long-term antidepressant use. A sample of 10 participants took part in cognitive interviews to test the understanding and acceptability of the questionnaire before its use in a mixed methods study. Two hundred and seventy-seven participants took part in The Attitudes and Preferences of People regarding Long-term Antidepressant Use for Depression (APPLAUD) Study, and 16 participants took part in the nested qualitative interview study. The findings from the questionnaire and interviews were interpreted together using a complementarity approach. The findings showed that patients’ beliefs and attitudes towards depression and long-term antidepressant use predicted intentions to start to come off antidepressants; however, most participants had li

Horizontal gene transfer via plasmids could favour cooperation in bacteria, because transfer of a cooperative gene turns non-cooperative cheats into cooperators. This hypothesis has received support from theoretical, genomic and experimental analyses. By contrast, we show here, with a comparative analysis across 51 diverse species, that genes for extracellular proteins, which are likely to act as cooperative 'public goods', were not more likely to be carried on either: (1) plasmids compared to chromosomes; or (2) plasmids that transfer at higher rates. Our results were supported by theoretical modelling which showed that, while horizontal gene transfer can help cooperative genes initially invade a population, it has less influence on the longer-term maintenance of cooperation. Instead, we found that genes for extracellular proteins were more likely to be on plasmids when they coded for pathogenic virulence traits, in pathogenic bacteria with a broad host-range.

Drug-resistant epilepsy (DRE) is characterized by fluctuating periods of remission and relapse during which it is easy for the voice of the patient to be overshadowed by a bio-medical focus. Since little is known about perceptions of illness severity in DRE, the purpose of this qualitative dissertation was to explore how a sample of participants perceived their epilepsy and how subjective perceptions of severity shaped the treatment journey. The rationale for the study was influenced by the assumption that the course of disease is impacted by what patients know and believe about the condition. A purposive sample was comprised of 35 participants with DRE of which 16 were undergoing in-patient evaluation for epilepsy surgery and 19 had signed a surgical consent. Constructivist grounded theory was used for data collection and analysis from which four analytic categories were developed: 1) “Epilepsy is an uphill thing”, 2) “It’s just not knowing”, 3) “Waving the white flag” and 4) “Battling with myself”. Our findings revealed that considerations of overall illness severity were arrived at after much inner debate centered around uncertainty, shared suffering and disease burden. Tensions and contradictions were expressed in relation to the impact of unpredictable seizures, yet illness severity was frequently downplayed, and participants found severity was difficult to rate. Pride was taken in coping well, yet acceptance of the epilepsy may also have contributed to a degree of treatment inertia. While epilepsy care felt directionless and life itself was on hold, other medical conditions were thought to be worse than epilepsy. We suggest that severity is a concept that is foundational to shared decision-making in epilepsy, and necessary to the timely execution of therapeutic options. Therefore, study recommendations include the importance of open conversations about illness severity. Nurses specialized in epilepsy care are well positioned to assess and influence patient and

IntroductionRandomised controlled trials (RCTs) are widely viewed to generate the most reliable medical knowledge. However, RCTs are not always scientifically necessary and therefore not always ethical. Unfortunately, it is not clear when an RCT is not necessary or how this should be established. This study seeks to systematically catalogue justifications offered throughout the medical and ethics literature for performing randomisation within clinical trials.Methods and analysisWe will systematically search electronic databases of the medical literature including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trials Register, Web of Science Proceedings, ClinicalTrials.gov; databases of philosophical literature including Philosopher's Index, Phil Papers, JSTOR, Periodicals Archive Online, Project MUSE, National Reference Centre for Bioethics; the library catalogue at the University of Ottawa; bibliographies of retrieved papers; and the grey literature. We will also pursue suggestions from experts in the fields of medical ethics, philosophy and clinical trial methodology. Article screening, selection and data extraction will be performed by two independent reviewers based on prespecified inclusion/exclusion criteria. A third reviewer will be consulted to resolve any discrepancies. We will then extract the reasons given to justify randomisation using methodology established to extract data in a defensible, systematic manner. We will track the reasons given, their frequency of use and changes over time. Finally, using grounded theory, we will combine the reasons into broader themes. These themes will form the foundation of our subsequent analysis from qualitative and quantitative perspectives. This review will map existing arguments that clinicians, ethicists and philosophers use to ethically justify randomisation in clinical trials.Ethics and disseminationNo research ethics board approval is necessary because we are not examining patient-le

There are well-known problems associated with the idea of (local) gravitational energy in general relativity. We offer a new perspective on those problems by comparison with Newtonian gravitation, and particularly geometrized Newtonian gravitation (i.e., Newton–Cartan theory). We show that there is a natural candidate for the energy density of a Newtonian gravitational field. But we observe that this quantity is gauge dependent, and that it cannot be defined in the geometrized (gauge-free) theory without introducing further structure. We then address a potential response by showing that there is an analogue to the Weyl tensor in geometrized Newtonian gravitation.

This booklet contains frequently asked questions--and their answers--about "quality circles," a factory program first introduced in Japan in which workers participate voluntarily in quality control and management decisions through various means of communication. Following an introductory chapter, the remainder of the booklet answers questions concerning: (1) objectives, (2) history, (3) quality circle operation, (4) themes, (5) management presentations, (6) consulting, (7) union views of quality circles, (8) potential problems, and (9) the role of the International Association of Quality Circles. (HTH)

This training manual provides information on the operation and function of "quality circles," a factory program introduced in Japan in which workers participate voluntarily in quality control and management decisions through various means of communication. Following an introduction, the manual presents a series of frequently asked questions about quality circles and then answers them. The next eight sections provide training modules dealing with the following topics: (1) problem prevention techniques, (2) brainstorming, (3) data collecting techniques, (4) data collection formats, (5) decision analysis using the Pareto chart (named for a nineteenth century European scholar), (6) basic cause and effect problem analysis, (7) process cause and effect problem analysis, and (8) ways to present ideas to management. Each chapter is followed by a worksheet and quiz. (HTH)

ObjectiveDespite its potential to offer seizure freedom, resective epilepsy surgery (RES) is seldom performed in patients 60 years of age or older. Demonstrating successful outcomes including an improved quality of life may raise awareness about the advantages of referring this underrepresented population for specialized evaluation. Accordingly, the authors investigated outcomes and life fulfillment in patients with an age ≥ 60 years who had undergone RES.MethodsAll patients who, at the age of 60 years or older, had undergone RES for medically refractory focal onset seizures at the authors' center were evaluated. A modified Liverpool Life Fulfillment (LLF) tool was administered postoperatively (maximum score 32). Seizure outcomes were classified according to the Engel classification system.ResultsTwelve patients underwent RES. The majority of patients (9 [75%] of 12) had at least 1 medical comorbidity in addition to seizures. The mean follow-up was 3.1 ± 2.1 years. At the time of the final follow-up, 11 (91.7%) of 12 patients were documented as having a good postsurgical outcome (Engel Class I-II). Half (6 of 12 patients) were completely seizure free (Engel Class IA). Liverpool Life Fulfillment (LLF) data were available for 11 patients. Following surgery, the mean LLF score was 26.7 ± 6. Eight patients (72.7%) noted excellent satisfaction with their RES, with 5 (45.5%) noting postoperative improvements in overall health.ConclusionsResective epilepsy surgery is safe and effective in patients with an age ≥ 60 years. Over 90% had a good surgical outcome, with 50% becoming completely seizure free despite 1 or more medical comorbidities in the majority. The study data indicated that an advancing age should not negatively influence consideration for RES.

The overall purpose of this review is to provide an independent look at the current work supported through the Foundation's Models for Change Initiative in Pennsylvania. In this summary of the report I will summarize the main findings.

George A. B. Dewar, editor of The Young England Library, plans to send the first two volumes. He hopes that President Roosevelt can review the books and give his approval. Dewar praises Roosevelt for his comments in an essay concerning what American boys should be, and adds that those comments apply to English boys, as well. Dewar closes by stating that Roosevelt's words on this topic "carry me away." After his signature, a note in parentheses says "author of Wildlife in Hampshire Highland, In Pursuit of the Trout, etc."