Cholinergic suppression: A postsynaptic mechanism of long-term associative learning

Food avoidance learning in the mollusc Pleurobranchaea entails reduction in the responsiveness of key brain interneurons in the feeding neural circuitry, the paracerebral feeding command interneurons (PCNs), to the neurotransmitter acetylcholine (AcCho). Food stimuli applied to the oral veil of an untrained animal depolarize the PCNs and induce the feeding motor program (FMP). Atropine (a muscarinic cholinergic antagonist) reversibly blocks the food-induced depolarization of the PCNs, implicating AcCho as the neurotransmitter mediating food detection. AcCho applied directly to PCN somata depolarizes them, indicating that the PCN soma membrane contains AcCho receptors and induces the FMP in the isolated central nervous system preparation. The AcCho response of the PCNs is mediated by muscariniclike receptors, since comparable depolarization is induced by muscarinic agonists (acetyl-ß -methylcholine, oxotremorine, pilocarpine), but not nicotine, and blocked by muscarinic antagonists (atropine, trifluoperazine). The nicotinic antagonist hexamethonium, however, blocked the AcCho response in four of six cases. When specimens are trained to suppress feeding behavior using a conventional food-avoidance learning paradigm (conditionally paired food and shock), AcCho applied to PCNs in the same concentration as in untrained animals causes little or no depolarization and does not initiate the FMP. Increasing the concentration of AcCho 10-100 times, however, induces weak PCN depolarization in trained specimens, indicating that learning diminishes but does not fully abolish AcCho responsiveness of the PCNs. This study proposes a cellular mechanism of long-term associative learning -- namely, postsynaptic modulation of neurotransmitter responsiveness in central neurons that could apply also to mammalian species

An Outbreak of Salmonella typhimurium at a teaching hospital

An outbreak of Salmonella typhimurium infection in December 1996 affected 52 patients, relatives, and staff of a large teaching hospital in southeast Queensland. Assorted sandwiches were identified as the vehicle of transmission. This article describes the outbreak investigation and demonstrates the importance of food hygiene and timely public health interventions

Ecological Effects of Fear: How Spatiotemporal Heterogeneity in Predation Risk Influences Mule Deer Access to Forage in a Sky‐Island System

Forage availability and predation risk interact to affect habitat use of ungulates across many biomes. Within sky‐island habitats of the Mojave Desert, increased availability of diverse forage and cover may provide ungulates with unique opportunities to extend nutrient uptake and/or to mitigate predation risk. We addressed whether habitat use and foraging patterns of female mule deer (Odocoileus hemionus) responded to normalized difference vegetation index (NDVI), NDVI rate of change (green‐up), or the occurrence of cougars (Puma concolor). Female mule deer used available green‐up primarily in spring, although growing vegetation was available during other seasons. Mule deer and cougar shared similar habitat all year, and our models indicated cougars had a consistent, negative effect on mule deer access to growing vegetation, particularly in summer when cougar occurrence became concentrated at higher elevations. A seemingly late parturition date coincided with diminishing NDVI during the lactation period. Sky‐island populations, rarely studied, provide the opportunity to determine how mule deer respond to growing foliage along steep elevation and vegetation gradients when trapped with their predators and seasonally limited by aridity. Our findings indicate that fear of predation may restrict access to the forage resources found in sky islands

The practices of apartheid as a war crime: a critical analysis

The human suffering caused by the political ideology of apartheid in South Africa during the Apartheid era (1948-1994) prompted worldwide condemnation and a variety of diplomatic and legal responses. Amongst these responses was the attempt to have apartheid recognised both as a crime against humanity in the 1973 Apartheid Convention as well as a war crime in Article 85(4)(c) of Additional Protocol I. This article examines the origins, nature and current status of the practices of apartheid as a war crime and its possible application to the Israeli-Palestinian conflict

Know and grow: A qualitative evaluation of a parent skills training intervention

Objective: This qualitative study examined the experience of parents of children and adolescents with eating disorders after having participated in a skills-based training intervention. Method: Participants were interviewed and transcripts were analysed using inductive thematic analysis. Results: Parent responses were organised around key themes of (1) effectiveness and acceptability of the intervention; (2) interpersonal experience of the group process; and (3) feedback on intervention content. Overall, the program was seen by parents to be highly relevant with direct application to supporting their child in home and hospital environments. Discussion: This study reports on preliminary evidence that skillsbased training is acceptable to parents and improves parent functioning including parent self-efficacy, and reduces psychological distress, anxiety, and burden. The study also demonstrated that the intervention can be delivered in a tertiary paediatric treatment setting and it may become cost-effective method for supporting parents and other carers. Future research is required on treatment efficacy and patient outcomes

Ethical considerations in determining standard of prevention packages for HIV prevention trials: Examining PrEP

The successful demonstration that antiretroviral (ARV) drugs can be used in diverse ways to reduce HIV acquisition or transmission risks – either taken as pre-exposure prophylaxis (PrEP) by those who are uninfected or as early treatment for prevention (T4P) by those living with HIV – expands the armamentarium of existing HIV prevention tools. These findings have implications for the design of future HIV prevention research trials. With the advent of multiple effective HIV prevention tools, discussions about the ethics and the feasibility of future HIV prevention trial designs have intensified. This article outlines arguments concerning the inclusion of newly established ARV-based HIV prevention interventions as standard of prevention in HIV prevention trials from multiple perspectives. Ultimately, there is a clear need to incorporate stakeholders in a robust discussion to determine the appropriate trial design for each study population

Evolutionary traditions and corporate law: the effectiveness and development of liquidation duty in China

This paper argues for updating and reform of the liquidation duty under Chinese corporate law. It adopts an evolutionary perspective on corporate law in the sense of asking whether the corporate laws co-evolve with, and adapt to the changing conditions of a country, rather than whether laws are converging towards a certain 'developed' model. In some jurisdictions, directors have a creditor-regarding duty when the company is insolvent or near insolvency and this duty is intended to constrain 'moral hazard' issues on the part of corporate insiders. In China, such moral hazard issues are mitigated by the liquidation duty. This paper argues that while the liquidation duty is relatively effective, it has created unfairness and undermined the value of formal insolvency law. Drawing on the experience of other jurisdictions especially the UK in relation to wrongful trading law, this paper suggests that a wrongful trading remedy and further restructuring measures might be introduced in China

Symptomatology of carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy

OBJECTIVE: To ascertain whether adverse effects experienced by people taking carbamazepine or oxcarbazepine could be attributed to carbamazepine- or oxcarbazepine-induced hyponatremia (COIH). METHODS: We performed an observational study, collecting data between 2017 and 2019 on serum sodium levels and adverse effects retrospectively in people with epilepsy while receiving treatment with either carbamazepine (CBZ) or oxcarbazepine (OXC). We defined hyponatremia as sodium level ≤134 mEq/L and severe hyponatremia as sodium level ≤128 mEq/L. Adverse effects experienced were compared between groups of individuals with and without hyponatremia. RESULTS: A total of 1370 people using CBZ or OXC were identified, of whom 410 had at least one episode of hyponatremia. We checked for symptoms related to the use of CBZ and OXC in 710 people (410 with and 300 without hyponatremia) and found relevant information in 688. Adverse effects occurred in 65% of people with hyponatremia compared to 21% with normal sodium levels (odds ratio [OR] 7.5, P ≤ .001) and in 83% of people with severe hyponatremia compared to 55% in those with mild hyponatremia (P ≤ .001). Significant predictors of adverse effects were the drug (OXC vs CBZ), and the number of concomitant anti-seizure medications. Dizziness (28% vs 6%), tiredness (22% vs 7%), instability (19% vs 3%), and diplopia (16% vs 4%) were reported more often in the hyponatremia group than in patients with normal levels. SIGNIFICANCE: People with COIH had a 7-fold increased risk of developing adverse effects during treatment. Clinicians should consider ascertainment of sodium levels in patients taking CBZ and OXC and act upon findings

Cost-effectiveness of alternative methods of surgical repair of inguinal hernia

Objectives: To assess the relative cost-effectiveness of laparoscopic methods of inguinal hernia repair compared with open flat mesh and open non-mesh repair. Methods: Data on the effectiveness of these alternatives came from three systematic reviews comparing: (i) laparoscopic methods with open flat mesh or non-mesh methods; (ii) open flat mesh with open non-mesh repair; and (iii) methods that used synthetic mesh to repair the hernia defect with those that did not. Data on costs were obtained from the authors of economic evaluations previously conducted alongside trials included in the reviews. A Markov model was used to model cost-effectiveness for a five-year period after the initial operation. The outcomes of the model were presented using a balance sheet approach and as cost per hernia recurrence avoided and cost per extra day at usual activities. Results: Open flat mesh was the most cost-effective method of preventing recurrences. Laparoscopic repair provided a shorter period of convalescence and less long-term pain compared with open flat mesh but was more costly. The mean incremental cost per additional day back at usual activities compared with open flat mesh was €38 and €80 for totally extraperitoneal and transabdominal preperitoneal repair, respectively. Conclusions: Laparoscopic repair is not cost-effective compared with open flat mesh repair in terms of cost per recurrence avoided. Decisions about the use of laparoscopic repair depend on whether the benefits (reduced pain and earlier return to usual activities) outweigh the extra costs and intraoperative risks. On the evidence presented here, these extra costs are unlikely to be offset by the short-term benefits of laparoscopic repair.Luke Vale, Adrian Grant, Kirsty McCormack, Neil W. Scott and the EU Hernia Trialists Collaboratio

Mach's principle: Exact frame-dragging via gravitomagnetism in perturbed Friedmann-Robertson-Walker universes with K=(±1,0)K = (\pm 1, 0)

We show that the dragging of the axis directions of local inertial frames by a weighted average of the energy currents in the universe is exact for all linear perturbations of any Friedmann-Robertson-Walker (FRW) universe with K = (+1, -1, 0) and of Einstein's static closed universe. This includes FRW universes which are arbitrarily close to the Milne Universe, which is empty, and to the de Sitter universe. Hence the postulate formulated by E. Mach about the physical cause for the time-evolution of the axis directions of inertial frames is shown to hold in cosmological General Relativity for linear perturbations. The time-evolution of axis directions of local inertial frames (relative to given local fiducial axes) is given experimentally by the precession angular velocity of gyroscopes, which in turn is given by the operational definition of the gravitomagnetic field. The gravitomagnetic field is caused by cosmological energy currents via the momentum constraint. This equation for cosmological gravitomagnetism is analogous to Ampere's law, but it holds also for time-dependent situtations. In the solution for an open universe the 1/r^2-force of Ampere is replaced by a Yukawa force which is of identical form for FRW backgrounds with $K = (-1, 0).$ The scale of the exponential cutoff is the H-dot radius, where H is the Hubble rate, and dot is the derivative with respect to cosmic time. Analogous results hold for energy currents in a closed FRW universe, K = +1, and in Einstein's closed static universe.Comment: 23 pages, no figures. Final published version. Additional material in Secs. I.A, I.J, III, V.H. Additional reference