Snca and Bdnf gene expression in the VTA and raphe nuclei of midbrain in chronically victorious and defeated male mice

The study aimed to analyze the mRNA levels of Snca and Bdnf genes in the ventral tegmental area (VTA) and raphe nuclei of the midbrain in male mice that had each won or defeated 20 encounters in daily agonistic interactions. Groups of animals that had the same winning and losing track record followed by a no-fight period for 14 days were also studied. Snca mRNA levels were increased in the raphe nuclei in the losers and in the VTA of the winners. After fighting deprivation Snca mRNA levels were decreased to the control level in both groups. Snca mRNA levels were similar to the control level in the VTA of the losers and in the raphe nuclei of the winners. However Snca gene expression was increased in these areas after no-fight period in the winners and losers in comparison with respective mRNA levels in the undeprived animals. Significant positive correlations were found between the mRNA levels of Snca and Bdnf genes in the raphe nuclei. It was concluded, that social experience affects Snca gene expression depending on brain areas and functional activity of monoaminergic systems in chronically victorious or defeated mice

Public health care resource allocation and the rule of rescue

In health care, a tension sometimes arises between the injunction to do as much good as possible with scarce resources and the injunction to rescue identifiable individuals in immediate peril, regardless of cost (the "Rule of Rescue". This tension can generate serious ethical and political difficulties for public policy makers faced with making explicit decisions about the public funding of controversial health technologies, such as costly new cancer drugs. In this paper we explore the appropriate role of the Rule of Rescue in public resource allocation decisions. We consider practical approaches to operationalising the Rule of Rescue from Australia and the UK before examining the relevance of individual moral imperatives to public policy making. We conclude that, whilst public policy makers in a humane society should facilitate exceptional departures from a cost effectiveness norm in clinical decisions about identified individuals, it is not so obvious that they should, as a matter of national public policy, except any one group of unidentified individuals within society from the rules of opportunity cost at the expense of all others

Impulse balance and framing effects in threshold public good games

In this paper, we revisit the evidence for framing effects in threshold public good games. Our particular focus is on why the probability of providing the public good appears to be higher in positive, give frames compared with negative, take frames. We show that the impulse balance theory can explain this effect. We also report a new experiment designed to test the predictions of the impulse balance theory. The results of the experiment fit well, both in quantitative and qualitative terms, with our predictions.</p

Public health care resource allocation and the rule of rescue

In health care, a tension sometimes arises between the injunction to do as much good as possible with scarce resources and the injunction to rescue identifiable individuals in immediate peril, regardless of cost (the "Rule of Rescue". This tension can generate serious ethical and political difficulties for public policy makers faced with making explicit decisions about the public funding of controversial health technologies, such as costly new cancer drugs. In this paper we explore the appropriate role of the Rule of Rescue in public resource allocation decisions. We consider practical approaches to operationalising the Rule of Rescue from Australia and the UK before examining the relevance of individual moral imperatives to public policy making. We conclude that, whilst public policy makers in a humane society should facilitate exceptional departures from a cost effectiveness norm in clinical decisions about identified individuals, it is not so obvious that they should, as a matter of national public policy, except any one group of unidentified individuals within society from the rules of opportunity cost at the expense of all others

Sensitive Coverage Saves Lives: Improving media portrayal of suicidal behaviour

The report outlines the results of consultations with journalists, suicide prevention agencies and mental health groups conducted by the journalism ethics charity MediaWise. It makes recommendations for action by media organisations and suicide prevention agencies

Waiting times and socioeconomic status: evidence from England

Waiting times for elective surgery, like hip replacement, are often referred to as an equitable rationing mechanism in publicly-funded healthcare systems because access to care is not based on socioeconomic status. Previous work has established that that this may not be the case and there is evidence of inequality in NHS waiting times favouring patients living in the least deprived neighbourhoods in England. We advance the literature by explaining variations of inequalities in waiting times in England in four different ways. First, we ask whether inequalities are driven by education rather than income. Our analysis shows that education and income deprivation have distinct effects on waiting time. Patients in the first quintile with least deprivation in education wait 9% less than patients in the second quintile and 14% less than patients in the third-to-fifth quintile. Patients in the fourth and fifth most income-deprived quintile wait about 7% longer than patients in the least deprived quintile. Second, we investigate whether inequalities arise "across" hospitals or "within" the hospital. The analysis provides evidence that most inequalities occur within hospitals rather than across hospitals. Moreover, failure to control for hospital fixed effects results in underestimation of the income gradient. Third, we explore whether inequalities arise across the entire waiting time distribution. Inequalities between better educated patients and other patients occur over large part of the waiting time distribution. Moreover we find that the education gradient becomes smaller for very long waiting. Fourth, we investigate whether the gradient may reflect the fact that patients with higher socioeconomic status have a different severity as proxied through a range of types and the number of diagnoses (in addition to age and gender) compared to those with lower socioeconomic status. We find no evidence that differences in severity explain the social gradient in waiting times

Understanding Harris' understanding of CEA: is cost effective resource allocation undone?

We summarise and evaluate Harris' criticisms of cost-effectiveness analysis (CEA) and the alternative processes he commends to health care decision makers. In contrast to CEA, Harris' asserts that individuals have a right to life-saving treatment that cannot be denied on the basis of their capacity to benefit. We conclude that, whilst Harris' work has challenged the proponents of CEA and quality-adjusted life years to be explicit about the method's indirect discriminatory characteristics, his arguments ignore important questions about what ‘lives saved’ mean. Harris also attempts to avoid opportunity cost by advocating the same chance of treatment for every person desiring treatment. Using a simple example, we illustrate that an ‘equal chances’ lottery is not in the interest of any patient, as it reduces the chance of treatment for all patients by leaving some of the health budget unspent

Exploring what lies behind public preferences for avoiding health losses caused by lapses in healthcare safety and patient lifestyle choices

© 2013 Singh et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Although many studies have identified public preferences for prioritising health care interventions based on characteristics of recipient or care, very few of them have examined the reasons for the stated preferences. We conducted an on-line person trade-off (PTO) study (N=1030) to investigate whether the public attach a premium to the avoidance of ill health associated with alternative types of responsibilities: lapses in healthcare safety, those caused by individual action or lifestyle choice; or genetic conditions. We found that the public gave higher priority to prevention of harm in a hospital setting such as preventing hospital associated infections than genetic disorder but drug administration errors were valued similar to genetic disorders. Prevention of staff injuries, lifestyle diseases and sports injuries, were given lower priority. In this paper we aim to understand the reasoning behind the responses by analysing comments provided by respondents to the PTO questions. Method: A majority of the respondents who participated in the survey provided brief comments explaining preferences in free text responses following PTO questions. This qualitative data was transformed into explicit codes conveying similar meanings. An overall coding framework was developed and a reliability test was carried out. Recurrent patterns were identified in each preference group. Comments which challenged the assumptions of hypothetical scenarios were also investigated. Results: NHS causation of illness and a duty of care were the most cited reasons to prioritise lapses in healthcare safety. Personal responsibility dominated responses for lifestyle related contexts, and many respondents mentioned that health loss was the result of the individual’s choice to engage in risky behaviour. A small proportion of responses questioned the assumptions underlying the PTO questions. However excluding these from the main analysis did not affect the conclusions. Conclusion: Although some responses indicated misunderstanding or rejection of assumptions we put forward, the results were still robust. The reasons put forward for responses differed between comparisons but responsibility was the most frequently cited. Most preference elicitation studies only focus on eliciting numerical valuations but allowing for qualitative data can augment understanding of preferences as well as verifying results.EPSRC through the MATCH programme(EP/F063822/1 and EP/G012393/1) and HERG within Brunel University

Are Individuals Fickle-Minded?

Game theory has been used to model large-scale social events — such as constitutional law, democratic stability, standard setting, gender roles, social movements, communication, markets, the selection of officials by means of elections, coalition formation, resource allocation, distribution of goods, and war — as the aggregate result of individual choices in interdependent decision-making. Game theory in this way assumes methodological individualism. The widespread observation that game theory predictions do not in general match observation has led to many attempts to repair game theory by creating behavioral game theory, which adds corrective terms to the game theoretic predictions in the hope of making predictions that better match observations. But for game theory to be useful in making predictions, we must be able to generalize from an individual’s behavior in one situation to that individual’s behavior in very closely similar situations. In other words, behavioral game theory needs individuals to be reasonably consistent in action if the theory is to have predictive power. We argue on the basis of experimental evidence that the assumption of such consistency is unwarranted. More realistic models of individual agents must be developed that acknowledge the variance in behavior for a given individual

Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS)

Background: Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients. A mutation in CHMP2B was recently identified in a Danish pedigree with autosomal dominant FTD. Subsequently, two unrelated patients with familial ALS, one of whom also showed features of FTD, were shown to carry missense mutations in CHMP2B. The initial aim of this study was to determine whether mutations in CHMP2B contribute more broadly to ALS pathogenesis. Methodology/Principal Findings: Sequencing of CHMP2B in 433 ALS cases from the North of England identified 4 cases carrying 3 missense mutations, including one novel mutation, p. Thr104Asn, none of which were present in 500 neurologically normal controls. Analysis of clinical and neuropathological data of these 4 cases showed a phenotype consistent with the lower motor neuron predominant (progressive muscular atrophy (PMA)) variant of ALS. Only one had a recognised family history of ALS and none had clinically apparent dementia. Microarray analysis of motor neurons from CHMP2B cases, compared to controls, showed a distinct gene expression signature with significant differential expression predicting disassembly of cell structure; increased calcium concentration in the ER lumen; decrease in the availability of ATP; down-regulation of the classical and p38 MAPK signalling pathways, reduction in autophagy initiation and a global repression of translation. Transfection of mutant CHMP2B into HEK-293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localisation demonstrated by CD63 staining and impairment of autophagy indicated by increased levels of LC3-II protein. These changes were absent in control cells transfected with wild-type CHMP2B. Conclusions/Significance: We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype