The Bernstein Memorial Lecture: The First Six Years

CICLOPs, the Center for International & Comparative Law Occasional Papers, could not be launched with a better issue than one dedicated to Duke Law\u27s named lecture series in the field, the Annual Herbert L. Bernstein Memorial Lecture in Comparative Law. Herbert Bernstein was Duke\u27s much-beloved professor of comparative law. The lecture series, established in Prof. Bernstein’s honor after his sudden death in 2001, has drawn leading scholars from all around the world to speak at Duke Law School on comparative law. This first issue of CICLOPs contains the text of the first six lectures, some of them previously published in hard-to-access venues and some not at all. As such, it serves as a tribute not only to Herbert Bernstein, but also to Duke Law\u27s vibrant and active comparative law community, which encompasses both numerous faculty members and also students pursuing Duke\u27s JD/LLM degree in international and comparative law as well as other student groups. The issue contains all lectures in the order in which they were delivered

Towards population coding principles in the primate premotor and parietal grasping network

As humans, the only way for us to interact with the world around us is by utilizing our highly trained motor system. Therefore, understanding how the brain generates movement is essential to understanding all aspects of human behavior. Despite the importance the motor system, the manner in which the brain prepares and executes movements, especially grasping movements, is still unclear. In this thesis I undertake a number of electrophysiological and computational experiments on macaque monkeys, primates showing similar grasping behavior to humans, to shed light on how grasping movements are planned and executed across distributed brain regions in both parietal and premotor cortices. Through these experiments, I reveal how the use of large-scale electrophysiological recording of hundreds of neurons simultaneously in primates allows the investigation of network computational principles essential for grasping, and I develop a series of analytical techniques for dissecting the large data sets collected from these experiments. In chapter 2.1 I show how large-scale parallel recordings can be leveraged to make behavioral predictions on single trials. The methods used to extract single-trial predictions varied in their performance, but population-based methods provided the most consistent and meaningful interpretation of the data. In addition, the success of these behavioral predictions could be used to make inferences about how areas differ in their contribution to preparation of grasping movements. It was found that while reaction time could be predicted from the population activity of either area, performance was significantly higher using the data from premotor cortex, suggesting that population activity in premotor cortex may have a more direct effect on behavior. In chapter 2.2 I show how preparation and movement intermingle and interact with one another on the continuum between immediate and withheld movement. Our population-based and dimensionality reduction techniques enable interpretation of the data, even when single neuron tuning properties are highly temporally and functionally complex. Activity in parietal cortex stabilizes during the memory period, while it continues to evolve in premotor cortex, revealing a decodable signature of time. Furthermore, activity during movement initiation clusters into two groups, movements initiated as fast as possible and movements from memory, showing how a state shift likely occurs on the border between these two types of actions. In chapter 2.3 I show that the question of how motor cortex controls movement is an ongoing issue in the field. I address crucial details about recent methodology used to extract rotational dynamics in motor cortex. I show how a simple neural network simulation and novel statistical test reveal properties of motor cortex not examined before, showing how models of movement generation can be essential tools in adding perspective to empirical results. Finally, in chapter 2.4 I show how the specificity of hand use can be used as a tool to dissociate levels of abstraction in the visual to motor transformation in parietal and premotor cortex. While preparatory activity is mostly hand-invariant in parietal cortex, activity in premotor cortex dissociates the intended hand use well before movement. Importantly, we show how appropriate dimensionality reduction techniques can disentangle the effects of multiple task parameters and find latent dimensions consistent between areas and animals. Together, the results of my experiments reinforce the importance of seeing the motor system not as a collection of individually tuned neurons, but as a dynamic network of neurons continuously acting together to produce the complex and flexible behavior we observe in all primates

Amplification of simian retroviral sequences from human recipients of baboon liver transplants

Investigations into the use of baboons as organ donors for human transplant recipients, a procedure called xenotransplantation, have raised the specter of transmitting baboon viruses to humans and possibly establishing new human infectious diseases. Retrospective analysis of tissues from two human transplant recipients with end-stage hepatic disease who died 70 and 27 days after the transplantation of baboon livers revealed the presence of two simian retroviruses of baboon origin, simian foamy virus (SFV) and baboon endogenous virus (BaEV), in multiple tissue compartments. The presence of baboon mitochondrial DNA was also detected in these same tissues, suggesting that xenogeneic 'passenger leukocytes' harboring latent or active viral infections had migrated from the xenografts to distant sites within the human recipients. The persistence of SFV and BaEV in human recipients throughout the posttransplant period underscores the potential infectious risks associated with xenotransplantation

Safety and efficacy of BAY 94–9027, an extended-half-life factor VIII, during minor surgical procedures in patients with severe haemophilia A

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Analysis of clinical benefit, harms, and cost-effectiveness of screening women for abdominal aortic aneurysm.

BACKGROUND: A third of deaths in the UK from ruptured abdominal aortic aneurysm (AAA) are in women. In men, national screening programmes reduce deaths from AAA and are cost-effective. The benefits, harms, and cost-effectiveness in offering a similar programme to women have not been formally assessed, and this was the aim of this study. METHODS: We developed a decision model to assess predefined outcomes of death caused by AAA, life years, quality-adjusted life years, costs, and the incremental cost-effectiveness ratio for a population of women invited to AAA screening versus a population who were not invited to screening. A discrete event simulation model was set up for AAA screening, surveillance, and intervention. Relevant women-specific parameters were obtained from sources including systematic literature reviews, national registry or administrative databases, major AAA surgery trials, and UK National Health Service reference costs. FINDINGS: AAA screening for women, as currently offered to UK men (at age 65 years, with an AAA diagnosis at an aortic diameter of ≥3·0 cm, and elective repair considered at ≥5·5cm) gave, over 30 years, an estimated incremental cost-effectiveness ratio of £30 000 (95% CI 12 000-87 000) per quality-adjusted life year gained, with 3900 invitations to screening required to prevent one AAA-related death and an overdiagnosis rate of 33%. A modified option for women (screening at age 70 years, diagnosis at 2·5 cm and repair at 5·0 cm) was estimated to have an incremental cost-effectiveness ratio of £23 000 (9500-71 000) per quality-adjusted life year and 1800 invitations to screening required to prevent one AAA-death, but an overdiagnosis rate of 55%. There was considerable uncertainty in the cost-effectiveness ratio, largely driven by uncertainty about AAA prevalence, the distribution of aortic sizes for women at different ages, and the effect of screening on quality of life. INTERPRETATION: By UK standards, an AAA screening programme for women, designed to be similar to that used to screen men, is unlikely to be cost-effective. Further research on the aortic diameter distribution in women and potential quality of life decrements associated with screening are needed to assess the full benefits and harms of modified options. FUNDING: UK National Institute for Health Research Health Technology Assessment programme

Participant experiences in a feasibility trial of supervised exercise training in adults with venous leg ulcers: a qualitative study.

Exercise training can improve lower‐limb cutaneous microvascular reactivity in adults with venous leg ulceration; however, there is a lack of research on patients' views about the acceptability and feasibility of exercise interventions. The aim of this study was to explore participants' experiences of the trial “Exploring the Feasibility of Implementing a Supervised Exercise Training and Compression Hosiery Intervention in Patients with Venous Ulceration” (FISCU). Semi‐structured face‐to‐face and telephone interviews were used to investigate participants' experiences (n = 16) of taking part in the FISCU trial. Data were analysed using thematic analysis. Three overarching themes were identified, along with 11 sub‐themes: (a) sedentary cautious living (because of pain and reduced mobility, treatment and perceived control, and advice to rest and be careful), (b) key components of the exercise trial (including motivation, an individualised intervention supervised by a specialist exercise professional, and satisfaction with the intervention), and (c) benefits of exercise (physical benefits and healing, psychological well‐being, positive impact on comorbidities, and an improved self‐management strategy). This study found that an exercise intervention was viewed by participants as positive, acceptable, and feasible while living with a venous leg ulcer. An individualised and supervised exercise programme was key to build confidence to exercise

Patient and provider experiences with virtual care during the COVID-19 pandemic: A mixed methods study

The COVID-19 pandemic prompted the rapid uptake of Virtual Care (VC). Positive patient outcomes with VC are previously reported but little is known about the experiences of patients and providers using VC during the pandemic. We aimed to describe patient and primary care provider experiences, satisfaction, perceptions, and attitudes to VC during the COVID-19 pandemic that might explain adoption of VC across the continuum of care and inform sustained uptake. We conducted a sequential explanatory mixed methods study using online surveys and virtual interviews with a convenience sample of primary care providers and patients in a Canadian province (July – December 2020). Eligible participants included patients and primary care providers using VC during the COVID-19 pandemic. Survey responses and interviews were analyzed using descriptive statistics and thematic analysis, respectively. Overall satisfaction was compared using the Mann-Whitney U test. Eighty-five patients and 94 primary care providers responded to the surveys. Patients reported higher overall satisfaction with VC than primary care providers (median [interquartile range]: 4.4 [4.0-4.7] and 3.7 [3.4-3.9] p \u3c 0.001). Ten patients and 11 primary care providers were interviewed. Both groups strongly appreciated VC’s increased access and convenience, identified the lack of compensation as a pre-pandemic barrier to providing VC, and reported willingness to continue VC post-COVID-19 pandemic. The COVID-19 pandemic provided an opportunity for patients and primary care providers to rapidly adopt VC with high satisfaction. Patients and primary care providers viewed VC positively due to its convenience and accessibility; both intend to continue using VC post-pandemic. Experience Framework This article is associated with the Staff & Provider Engagement lens of The Beryl Institute Experience Framework (https://www.theberylinstitute.org/ExperienceFramework). Access other PXJ articles related to this lens. Access other resources related to this lens

Outcomes of aortic aneurysm surgery in England : a nationwide cohort study using hospital admissions data from 2002 to 2015

Background The United Kingdom aortic aneurysms (AA) services have undergone reconfiguration to improve outcomes. The National Health Service collects data on all hospital admissions in England. The complex administrative datasets generated have the potential to be used to monitor activity and outcomes, however, there are challenges in using these data as they are primarily collected for administrative purposes. The aim of this study was to develop standardised algorithms with the support of a clinical consensus group to identify all AA activity, classify the AA management into clinically meaningful case mix groups and define outcome measures that could be used to compare outcomes among AA service providers. \ud Methods In-patient data about aortic aneurysm (AA) admissions from the 2002/03 to 2014/15 were acquired. A stepwise approach, with input from a clinical consensus group, was used to identify relevant cases. The data is primarily coded into episodes, these were amalgamated to identify admissions; admissions were linked to understand patient pathways and index admissions. Cases were then divided into case-mix groups based upon examination of individually sampled and aggregate data. Consistent measures of outcome were developed, including length of stay, complications within the index admission, post-operative mortality and re-admission. Results Several issues were identified in the dataset including potential conflict in identifying emergency and elective cases and potential confusion if an inappropriate admission definition is used. Ninety six thousand seven hundred thirty-five patients were identified using the algorithms developed in this study to extract AA cases from Hospital episode statistics. From 2002 to 2015, 83,968 patients (87% of all cases identified) underwent repair for AA and 12,767 patients (13% of all cases identified) died in hospital without any AA repair. Six thousand three hundred twenty-nine patients (7.5%) had repair for complex AA and 77,639 (92.5%) had repair for infra-renal AA. Conclusion The proposed methods define homogeneous clinical groups and outcomes by combining administrative codes in the data. These methodologically robust methods can help examine outcomes associated with previous and current service provisions and aid future reconfiguration of aortic aneurysm surgery services