Chronic voluntary alcohol consumption causes persistent cognitive deficits and cortical cell loss in a rodent model

Chronic alcohol use is associated with cognitive decline that impedes behavioral change during rehabilitation. Despite this, addiction therapy does not address cognitive deficits, and there is poor understanding regarding the mechanisms that underlie this decline. We established a rodent model of chronic voluntary alcohol use to measure ensuing cognitive effects and underlying pathology. Rats had intermittent access to alcohol or an isocaloric solution in their home cage under voluntary 2-bottle choice conditions. In Experiments 1 and 2 cognition was assessed using operant touchscreen chambers. We examined performance in a visual discrimination and reversal task (Experiment 1), and a 5-choice serial reaction time task (Experiment 2). For Experiment 3, rats were perfused immediately after cessation of alcohol access period, and volume, cell density and microglial populations were assessed in the prefrontal cortex and striatum. Volume was assessed using the Cavalieri probe, while cell and microglial counts were estimated using unbiased stereology with an optical fractionator. Alcohol-exposed and control rats showed comparable acquisition of pairwise discrimination; however, performance was impaired when contingencies were reversed indicating reduced behavioral flexibility. When tested in a 5-choice serial reaction time task alcohol-exposed rats showed increased compulsivity and increased attentional bias towards a reward associated cue. Consistent with these changes, we observed decreased cell density in the prefrontal cortex. These findings confirm a detrimental effect of chronic alcohol and establish a model of alcohol-induced cognitive decline following long-term voluntary intake that may be used for future intervention studies

Probabilistic design of optical transmission systems

Traditionally, optical fiber nonlinearity is considered a limiting factor for transmission systems. Nevertheless, from a system design perspective this nonlinearity can be exploited to minimize the impact of uncertainty on the system performance. A consequence of this is that it becomes beneficial to consider the uncertainty at the design stage, resulting in a probabilistic design, rather than conventional design approaches whereby uncertainty is added by way of system margins to a deterministic design. In this paper, we conduct extensive experimental measurements to quantify the impact of uncertainty for a multispan wavelength division multiplexed system transmitting 100 GbE or 200 GbE as dual polarization quadrature phase-shift keying (QPSK) or 16 quadrature amplitude modulation (16QAM), respectively. The impact of uncertainty in the power launched into a span is assessed for a 10 × 80 km link. For dual polarization (DP)-QPSK, the intralink power deviation with the probabilistic design with 100% reliability is ±1.3 dB falling to 99% reliability with ±1.6 dB. In contrast, for DP-16QAM maximum deviation for 100% reliability is ±0.5 dB falling to 99% for ±0.6 dB. Following this, we consider the interplay between polarization dependent loss (PDL) and fiber nonlinearity over an 8 × 80 km system again for both DP-QPSK and DP-16QAM. A system Q variation of less than 0.15 dB due to the interaction between PDL and fiber nonlinearity is observed for 99.9% of examined PDL values for DP-QPSK and DP-16QAM, thereby allowing the two effects to be considered separately.This research was supported by a Ciena University collaborative research grant. The work of H.-M. Chin was supported in part by a Ph.D. studentship from Ciena and in part by EU ICONE Project under Grant #608099. The work of S. J. Savory was supported by a Senior Research Fellowship from the RAEng/The Leverhulme Trust

Histopathology of melanocytic lesions in a family with an inherited BAP1 mutation

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Human-animal interactions and machine-animal interactions in animals under human care: a summary of stakeholder and researcher perceptions and future directions

Animals under human care are exposed to a potentially large range of both familiar and unfamiliar humans. Human-animal interactions vary across settings, and individuals, with the nature of the interaction being affected by a suite of different intrinsic and extrinsic factors. These interactions can be described as positive, negative or neutral. Across some industries, there has been a move towards the development of technologies to support or replace human interaction with animals. Whilst this has many benefits, there can also be challenges associated with increased technology use. A day-long Animal Welfare Research Network workshop was hosted at Harper Adams University, UK, with the aim of bringing together stakeholders and researchers (n = 38) from the companion, farm and zoo animal fields, to discuss benefits, challenges and limitations of human-animal interactions and machine-animal interactions for animals under human care and create a list of future research priorities. The workshop consisted of four talks from experts within these areas, followed by break-out room discussions. This work is the outcome of that workshop. The key recommendations are that approaches to advancing the scientific discipline of machine-animal interactions in animals under human care should focus on: (1) interdisciplinary collaboration; (2) development of validated methods; (3) incorporation of an animal-centred perspective; (4) a focus on promotion of positive animal welfare states (not just avoidance of negative states); and (5) an exploration of ways that machines can support a reduction in the exposure of animals to negative human-animal interactions to reduce negative, and increase positive, experiences for animals

The bashful and the boastful : prestigious leaders and social change in Mesolithic Societies

The creation and maintenance of influential leaders and authorities is one of the key themes of archaeological and historical enquiry. However the social dynamics of authorities and leaders in the Mesolithic remains a largely unexplored area of study. The role and influence of authorities can be remarkably different in different situations yet they exist in all societies and in almost all social contexts from playgrounds to parliaments. Here we explore the literature on the dynamics of authority creation, maintenance and contestation in egalitarian societies, and discuss the implications for our interpretation and understanding of the formation of authorities and leaders and changing social relationships within the Mesolithic

Evidence-based medicine in primary care: qualitative study of family physicians

BACKGROUND: The objectives of this study were: a) to examine physician attitudes to and experience of the practice of evidence-based medicine (EBM) in primary care; b) to investigate the influence of patient preferences on clinical decision-making; and c) to explore the role of intuition in family practice. METHOD: Qualitative analysis of semi-structured interviews of 15 family physicians purposively selected from respondents to a national survey on EBM mailed to a random sample of Canadian family physicians. RESULTS: Participants mainly welcomed the promotion of EBM in the primary care setting. A significant number of barriers and limitations to the implementation of EBM were identified. EBM is perceived by some physicians as a devaluation of the 'art of medicine' and a threat to their professional/clinical autonomy. Issues regarding the trustworthiness and credibility of evidence were of great concern, especially with respect to the influence of the pharmaceutical industry. Attempts to become more evidence-based often result in the experience of conflicts. Patient factors exert a powerful influence on clinical decision-making and can serve as trumps to research evidence. A widespread belief that intuition plays a vital role in primary care reinforced views that research evidence must be considered alongside other factors such as patient preferences and the clinical judgement and experience of the physician. DISCUSSION: Primary care physicians are increasingly keen to consider research evidence in clinical decision-making, but there are significant concerns about the current model of EBM. Our findings support the proposed revisions to EBM wherein greater emphasis is placed on clinical expertise and patient preferences, both of which remain powerful influences on physician behaviour

Patterns of care and survival for adolescents and young adults with acute leukaemia – a population-based study

We report a population-based study of patterns of care and survival for people with acute leukaemia diagnosed at age 15–29 years during 1984–94 in regions of England and Wales covered by specialist leukaemia registries. There were 879 patients: 417 with acute lymphoblastic leukaemia (ALL) and 462 with acute myeloid leukaemia (AML). For ALL, actuarial survival rates were 43% at 5 years after diagnosis and 37% at 10 years. Survival improved significantly between 1984–88 and 1989–94 for those aged 15–19 at diagnosis. Patients entered in national clinical trials and those not entered had similar survival rates. Survival rates were similar at teaching and non-teaching hospitals and at hospitals treating different numbers of study patients per year. For AML, survival rates were 42% at 5 years after diagnosis and 39% at 10 years. Survival improved significantly between 1984–88 and 1989–94. Patients entered in the Medical Research Council AML10 trial had a higher survival rate than those who were in the earlier AML9 trial. Survival did not vary with category of hospital. We conclude that survival has improved for adolescents and young adults with acute leukaemia but that there is at present no evidence that centralized treatment results in a survival benefit for patients in this age group. © 1999 Cancer Research Campaig

The feasibility of population screening for paroxysmal atrial fibrillation using hand-held electrocardiogram devices

Background and Aims There are few data on the feasibility of population screening for paroxysmal AF using hand-held ECG devices outside a specialist setting or in people over the age of 75. We investigated the feasibility of screening when conducted without face-to-face contact (‘remote’) or via in-person appointments in primary care, and explored impact of age on screening outcomes. Methods People aged ≥65 years from 13 general practices in England participated in screening during 2019-20. This involved attending a practice nurse appointment (10 practices) or receiving an ECG device by post (3 practices). Participants were asked to use a handheld ECG for 1-4 weeks. Screening outcomes included: uptake, quality of ECGs, AF detection rates, and uptake of anticoagulation if AF was detected. Results Screening was carried out by 2,141 (87.5%) of people invited to practice nurse-led screening and by 288 (90.0%) invited to remote screening. At least 56 interpretable ECGs were provided by 98.0% of participants who participated for 3 weeks, with no significant differences by setting or age, except people aged 85 or over (91.1%). Overall, 2.6% (64/2,429) screened participants had AF, with detection rising with age (9.2% in people aged 85 or over). 53/64 (82.8%) people with AF commenced anticoagulation. Uptake of anticoagulation did not vary by age. Conclusion Population screening for paroxysmal AF is feasible in general practice and without face-to-face contact, and in all ages over 64 years, including in people aged 85 and over