Adaptable history biases in human perceptual decisions

When making choices under conditions of perceptual uncertainty, past experience can play a vital role. However, it can also lead to biases that worsen decisions. Consistent with previous observations, we found that human choices are influenced by the success or failure of past choices even in a standard two-alternative detection task, where choice history is irrelevant. The typical bias was one that made the subject switch choices after a failure. These choice history biases led to poorer performance and were similar for observers in different countries. They were well captured by a simple logistic regression model that had been previously applied to describe psychophysical performance in mice. Such irrational biases seem at odds with the principles of reinforcement learning, which would predict exquisite adaptability to choice history. We therefore asked whether subjects could adapt their irrational biases following changes in trial order statistics. Adaptability was strong in the direction that confirmed a subject's default biases, but weaker in the opposite direction, so that existing biases could not be eradicated. We conclude that humans can adapt choice history biases, but cannot easily overcome existing biases even if irrational in the current context: adaptation is more sensitive to confirmatory than contradictory statistics

Environment-specific combinatorial cis-regulation in synthetic promoters

When a cell's environment changes, a large transcriptional response often takes place. The exquisite sensitivity and specificity of these responses are controlled in large part by the combinations of cis-regulatory elements that reside in gene promoters and adjacent control regions. Here, we present a study aimed at accurately modeling the relationship between combinations of cis-regulatory elements and the expression levels they drive in different environments. We constructed four libraries of synthetic promoters in yeast, consisting of combinations of transcription factor binding sites and assayed their expression in four different environments. Thermodynamic models relating promoter sequences to their corresponding four expression levels explained at least 56% of the variation in expression in each library through the different conditions. Analyses of these models suggested that a large fraction of regulated gene expression is explained by changes in the effective concentration of sequence-specific transcription factors, and we show that in most cases, the corresponding transcription factors are expressed in a pattern that is predicted by the thermodynamic models. Our analysis uncovered two binding sites that switch from activators to repressors in different environmental conditions. In both the cases, the switch was not the result of a single transcription factor changing regulatory modes, but most likely due to competition between multiple factors binding to the same site. Our analysis suggests that this mode of regulation allows for large and steep changes in expression in response to changing transcription factor concentrations. Our results demonstrate that many complex changes in gene expression are accurately explained by simple changes in the effective concentrations of transcription factors

Mental health: A cause or consequence of injury? A population-based matched cohort study

BACKGROUND: While a number of studies report high prevalence of mental health problems among injured people, the temporal relationship between injury and mental health service use has not been established. This study aimed to quantify this relationship using 10 years of follow-up on a population-based cohort of hospitalised injured adults. METHODS: The Manitoba Injury Outcome Study is a retrospective population-based matched cohort study that utilised linked administrative data from Manitoba, Canada, to identify an inception cohort (1988–1991) of hospitalised injured cases (ICD-9-CM 800–995) aged 18–64 years (n = 21,032), which was matched to a non-injured population-based comparison group (n = 21,032). Pre-injury comorbidity and post-injury mental health data were obtained from hospital and physician claims records. Negative Binomial regression was used to estimate adjusted rate ratios (RRs) to measure associations between injury and mental health service use. RESULTS: Statistically significant differences in the rates of mental health service use were observed between the injured and non-injured, for the pre-injury year and every year of the follow-up period. The injured cohort had 6.56 times the rate of post-injury mental health hospitalisations (95% CI 5.87, 7.34) and 2.65 times the rate of post-injury mental health physician claims (95% CI 2.53, 2.77). Adjusting for comorbidities and pre-existing mental health service use reduced the hospitalisations RR to 3.24 (95% CI 2.92, 3.60) and the physician claims RR to 1.53 (95% CI 1.47, 1.59). CONCLUSION: These findings indicate the presence of pre-existing mental health conditions is a potential confounder when investigating injury as a risk factor for subsequent mental health problems. Collaboration with mental health professionals is important for injury prevention and care, with ongoing mental health support being a clearly indicated service need by injured people and their families. Public health policy relating to injury prevention and control needs to consider mental health strategies at the primary, secondary and tertiary level

Glucocorticoid Effects on the Programming of AT1b Angiotensin Receptor Gene Methylation and Expression in the Rat

Adverse events in pregnancy may ‘programme’ offspring for the later development of cardiovascular disease and hypertension. Previously, using a rodent model of programmed hypertension we have demonstrated the role of the renin-angiotensin system in this process. More recently we showed that a maternal low protein diet resulted in undermethylation of the At1b angiotensin receptor promoter and the early overexpression of this gene in the adrenal of offspring. Here, we investigate the hypothesis that maternal glucocorticoid modulates this effect on fetal DNA methylation and gene expression. We investigated whether treatment of rat dams with the 11β-hydroxylase inhibitor metyrapone, could prevent the epigenetic and gene expression changes we observed. Offspring of mothers subjected to a low protein diet in pregnancy showed reduced adrenal Agtr1b methylation and increased adrenal gene expression as we observed previously. Treatment of mothers with metyrapone for the first 14 days of pregnancy reversed these changes and prevented the appearance of hypertension in the offspring at 4 weeks of age. As a control for non-specific effects of programmed hypertension we studied offspring of mothers treated with dexamethasone from day 15 of pregnancy and showed that, whilst they had raised blood pressure, they failed to show any evidence of Agtr1b methylation or increase in gene expression. We conclude that maternal glucocorticoid in early pregnancy may induce changes in methylation and expression of the Agtr1b gene as these are clearly reversed by an 11 beta-hydroxylase inhibitor. However in later pregnancy a converse effect with dexamethasone could not be demonstrated and this may reflect either an alternative mechanism of this glucocorticoid or a stage-specific influence

The Difference in Pharmacists’ Interventions across the Diverse Settings in a Children’s Hospital

Aims: This study aimed to document and compare the nature of clinical pharmacists’ interventions made in different practice settings within a children’s hospital. Methods: The primary investigator observed and documented all clinical interventions performed by clinical pharmacists for between 35–37 days on each of the five study wards from the three practice settings, namely general medical, general surgical and hematology-oncology. The rates, types and significance of the pharmacists’ interventions in the different settings were compared.Results: A total of 982 interventions were documented, related to the 16,700 medication orders reviewed on the five wards in the three practice settings over the duration of the study. Taking medication histories and/or patient counselling were the most common pharmacists’ interventions in the general settings; constituting more than half of all interventions. On the Hematology-Oncology Ward the pattern was different with drug therapy changes being the most common interventions (n = 73/195, 37.4% of all interventions). Active interventions (pharmacists’ activities leading to a change in drug therapy) constituted less than a quarter of all interventions on the general medical and surgical wards compared to nearly half on thespecialty Hematology-Oncology Ward. The majority (n = 37/42, 88.1%) of a random sample of the active interventions reviewed were rated as clinically significant. Dose adjustment was the most frequent active interventions in the general settings, whilst drug addition constituted the most common active interventions on the Hematology-Oncology Ward. The degree of acceptance of pharmacists’ active interventions by prescribers was high (n = 223/244, 91.4%).Conclusions: The rate of pharmacists’ active interventions differed across different practice settings, being most frequent in the specialty hematology-oncology setting. The nature and type of the interventions documented in the hematologyoncology were also different compared to those in the general medical and surgical settings

Relacao entre o nivel de atividade fisica estimado pelo Baltimore Activity Scale for Intermittent Claudication e a pedometria em pacientes com claudicacao intermitente

CONTEXTO: Os pacientes com claudicação intermitente apresentam níveis reduzidos de atividade física. A Baltimore Activity Scale for Intermittent Claudication (BASIC) foi validada para quantificar o nível de atividade física destes pacientes. No entanto, esta validação se baseou em apenas dois dias de monitoramento com acelerômetros, de modo que ainda permanece incerto se a BASIC fornece informações sobre os níveis de atividade física semanal. OBJETIVO: Analisar a correlação entre o nível de atividade física estimada pela BASIC e o nível obtido pelo pedômetro em uma semana, em pacientes com claudicação intermitente. MÉTODOS: Foram estudados 150 pacientes com claudicação intermitente, com idade entre 30 e 80 anos. Foram obtidos os dados sociodemográficos e verificada a presença de comorbidades e de fatores de risco cardiovascular, e a BASIC. O pedômetro foi utilizado por sete dias consecutivos, sendo a análise feita em três diferentes períodos de monitorização (todos os dias, dias da semana e do fim de semana). RESULTADOS: Foi observada correlação entre a BASIC e a média de passos de todos os dias (rho=0,343; p<0,001), dos dias de semana (rho=0,336; p<0,001) e dos dias do final de semana (rho=0,317; p<0,001). CONCLUSÃO: Em pacientes com claudicação intermitente, o nível de atividade física estimado pela BASIC se correlaciona com o nível de atividade física semanal

Antibody-Based Detection and Inhibition of Vaginolysin, the Gardnerella vaginalis Cytolysin

Bacterial vaginosis (BV) is the most common vaginal infection worldwide and is associated with significant adverse sequelae. We have recently characterized vaginolysin (VLY), the human-specific cytotoxin produced by Gardnerella vaginalis and believed to play a critical role in the pathogenesis of BV and its associated morbidities. We hypothesize that novel antibody-based strategies may be useful for detection of VLY and for inhibition of its toxic effects on human cells. Using purified toxin as an immunogen, we generated polyclonal rabbit immune serum (IS) against VLY. A western blot of G. vaginalis lysate was probed with IS and a single band (57 kD) identified. Immunofluorescence techniques using IS detected VLY production by G. vaginalis. In addition, we have developed a sandwich ELISA assay capable of VLY quantification at ng/ml concentrations in the supernatant of growing G. vaginalis. To investigate the potential inhibitory role of IS on VLY-mediated cell lysis, we exposed human erythrocytes to VLY or VLY pretreated with IS and determined the percent hemolysis. Pretreatment with IS resulted in a significant reduction in VLY-mediated lysis. Similarly, both human cervical carcinoma cells and vaginal epithelial cells exhibited reduced cytolysis following exposure to VLY with IS compared to VLY alone. These results confirm that antibody-based techniques are an effective means of VLY detection. Furthermore, VLY antiserum functions as an inhibitor of VLY–CD59 interaction, mitigating cell lysis. These strategies may have a potential role in the diagnosis and treatment of BV

The Early Prevention of Obesity in CHildren (EPOCH) Collaboration - an Individual Patient Data Prospective Meta-Analysis

BackgroundEfforts to prevent the development of overweight and obesity have increasingly focused early in the life course as we recognise that both metabolic and behavioural patterns are often established within the first few years of life. Randomised controlled trials (RCTs) of interventions are even more powerful when, with forethought, they are synthesised into an individual patient data (IPD) prospective meta-analysis (PMA). An IPD PMA is a unique research design where several trials are identified for inclusion in an analysis before any of the individual trial results become known and the data are provided for each randomised patient. This methodology minimises the publication and selection bias often associated with a retrospective meta-analysis by allowing hypotheses, analysis methods and selection criteria to be specified a priori.Methods/DesignThe Early Prevention of Obesity in CHildren (EPOCH) Collaboration was formed in 2009. The main objective of the EPOCH Collaboration is to determine if early intervention for childhood obesity impacts on body mass index (BMI) z scores at age 18-24 months. Additional research questions will focus on whether early intervention has an impact on children\u27s dietary quality, TV viewing time, duration of breastfeeding and parenting styles. This protocol includes the hypotheses, inclusion criteria and outcome measures to be used in the IPD PMA. The sample size of the combined dataset at final outcome assessment (approximately 1800 infants) will allow greater precision when exploring differences in the effect of early intervention with respect to pre-specified participant- and intervention-level characteristics.DiscussionFinalisation of the data collection procedures and analysis plans will be complete by the end of 2010. Data collection and analysis will occur during 2011-2012 and results should be available by 2013.<br /

A survey of community members' perceptions of medical errors in Oman

<p>Abstract</p> <p>Background</p> <p>Errors have been the concern of providers and consumers of health care services. However, consumers' perception of medical errors in developing countries is rarely explored. The aim of this study is to assess community members' perceptions about medical errors and to analyse the factors affecting this perception in one Middle East country, Oman.</p> <p>Methods</p> <p>Face to face interviews were conducted with heads of 212 households in two villages in North Al-Batinah region of Oman selected because of close proximity to the Sultan Qaboos University (SQU), Muscat, Oman. Participants' perceived knowledge about medical errors was assessed. Responses were coded and categorised. Analyses were performed using Pearson's χ², Fisher's exact tests, and multivariate logistic regression model wherever appropriate.</p> <p>Results</p> <p>Seventy-eight percent (n = 165) of participants believed they knew what was meant by medical errors. Of these, 34% and 26.5% related medical errors to wrong medications or diagnoses, respectively. Understanding of medical errors was correlated inversely with age and positively with family income. Multivariate logistic regression revealed that a one-year increase in age was associated with a 4% reduction in perceived knowledge of medical errors (CI: 1% to 7%; p = 0.045). The study found that 49% of those who believed they knew the meaning of medical errors had experienced such errors. The most common consequence of the errors was severe pain (45%). Of the 165 informed participants, 49% felt that an uncaring health care professional was the main cause of medical errors. Younger participants were able to list more possible causes of medical errors than were older subjects (Incident Rate Ratio of 0.98; p < 0.001).</p> <p>Conclusion</p> <p>The majority of participants believed they knew the meaning of medical errors. Younger participants were more likely to be aware of such errors and could list one or more causes.</p