Metastability in the dilute Ising model

Consider Glauber dynamics for the Ising model on the hypercubic lattice with a positive magnetic field. Starting from the minus configuration, the system initially settles into a metastable state with negative magnetization. Slowly the system relaxes to a stable state with positive magnetization. Schonmann and Shlosman showed that in the two dimensional case the relaxation time is a simple function of the energy required to create a critical Wulff droplet. The dilute Ising model is obtained from the regular Ising model by deleting a fraction of the edges of the underlying graph. In this paper we show that even an arbitrarily small dilution can dramatically reduce the relaxation time. This is because of a catalyst effect---rare regions of high dilution speed up the transition from minus phase to plus phase.Comment: 49 page

Can We “Hedge” against the Development of Antiviral Resistance among Pandemic Influenza Viruses?

David K. Shay and Benjamin Ridenhour discuss a modeling study predicting that stockpiling a secondary antiviral for use early in a flu pandemic can forestall resistance to the primary stockpiled drug

Centre selection for clinical trials and the generalisability of results: a mixed methods study.

BACKGROUND: The rationale for centre selection in randomised controlled trials (RCTs) is often unclear but may have important implications for the generalisability of trial results. The aims of this study were to evaluate the factors which currently influence centre selection in RCTs and consider how generalisability considerations inform current and optimal practice. METHODS AND FINDINGS: Mixed methods approach consisting of a systematic review and meta-summary of centre selection criteria reported in RCT protocols funded by the UK National Institute of Health Research (NIHR) initiated between January 2005-January 2012; and an online survey on the topic of current and optimal centre selection, distributed to professionals in the 48 UK Clinical Trials Units and 10 NIHR Research Design Services. The survey design was informed by the systematic review and by two focus groups conducted with trialists at the Birmingham Centre for Clinical Trials. 129 trial protocols were included in the systematic review, with a total target sample size in excess of 317,000 participants. The meta-summary identified 53 unique centre selection criteria. 78 protocols (60%) provided at least one criterion for centre selection, but only 31 (24%) protocols explicitly acknowledged generalisability. This is consistent with the survey findings (n = 70), where less than a third of participants reported generalisability as a key driver of centre selection in current practice. This contrasts with trialists' views on optimal practice, where generalisability in terms of clinical practice, population characteristics and economic results were prime considerations for 60% (n = 42), 57% (n = 40) and 46% (n = 32) of respondents, respectively. CONCLUSIONS: Centres are rarely enrolled in RCTs with an explicit view to external validity, although trialists acknowledge that incorporating generalisability in centre selection should ideally be more prominent. There is a need to operationalize 'generalisability' and incorporate it at the design stage of RCTs so that results are readily transferable to 'real world' practice

Entry screening to delay local transmission of 2009 pandemic influenza A (H1N1)

<p>Abstract</p> <p>Background</p> <p>After the WHO issued the global alert for 2009 pandemic influenza A (H1N1), many national health agencies began to screen travelers on entry in airports, ports and border crossings to try to delay local transmission.</p> <p>Methods</p> <p>We reviewed entry screening policies adopted by different nations and ascertained dates of official report of the first laboratory-confirmed imported H1N1 case and the first laboratory-confirmed untraceable or 'local' H1N1 case.</p> <p>Results</p> <p>Implementation of entry screening policies was associated with on average additional 7-12 day delays in local transmission compared to nations that did not implement entry screening, with lower bounds of 95% confidence intervals consistent with no additional delays and upper bounds extending to 20-30 day additional delays.</p> <p>Conclusions</p> <p>Entry screening may lead to short-term delays in local transmission of a novel strain of influenza virus. The resources required for implementation should be balanced against the expected benefits of entry screening.</p

Selection at a single locus leads to widespread expansion of toxoplasma gondii lineages that are virulent in mice

The determinants of virulence are rarely defined for eukaryotic parasites such as T. gondii, a widespread parasite of mammals that also infects humans, sometimes with serious consequences. Recent laboratory studies have established that variation in a single secreted protein, a serine/threonine kinase known as ROPO18, controls whether or not mice survive infection. Here, we establish the extent and nature of variation in ROP18among a collection of parasite strains from geographically diverse regions. Compared to other genes, ROP18 showed extremely high levels of diversification and changes in expression level, which correlated with severity of infection in mice. Comparison with an out-group demonstrated that changes in the upstream region that regulates expression of ROP18 led to an historical increase in the expression and exposed the protein to diversifying selective pressure. Surprisingly, only three atypically distinct protein variants exist despite marked genetic divergence elsewhere in the genome. These three forms of ROP18 are likely adaptations for different niches in nature, and they confer markedly different virulence to mice. The widespread distribution of a single mouse-virulent allele among geographically and genetically disparate parasites may have consequences for transmission and disease in other hosts, including humans

Second-to-Fourth Digit Ratio Has a Non-Monotonic Impact on Altruism

Gene-culture co-evolution emphasizes the joint role of culture and genes for the emergence of altruistic and cooperative behaviors and behavioral genetics provides estimates of their relative importance. However, these approaches cannot assess which biological traits determine altruism or how. We analyze the association between altruism in adults and the exposure to prenatal sex hormones, using the second-to-fourth digit ratio. We find an inverted U-shaped relation for left and right hands, which is very consistent for men and less systematic for women. Subjects with both high and low digit ratios give less than individuals with intermediate digit ratios. We repeat the exercise with the same subjects seven months later and find a similar association, even though subjects' behavior differs the second time they play the game. We then construct proxies of the median digit ratio in the population (using more than 1000 different subjects), show that subjects' altruism decreases with the distance of their ratio to these proxies. These results provide direct evidence that prenatal events contribute to the variation of altruistic behavior and that the exposure to fetal hormones is one of the relevant biological factors. In addition, the findings suggest that there might be an optimal level of exposure to these hormones from social perspective.Financial support from the Spanish Ministry of Science and Innovation (ECO2010{17049; ECO2009-09120), the Government of Andalusia Project for Excellence in Research (P07.SEJ.02547), the Government of the Basque Country (IT-223–07) and Fundacion Ramon Areces (I+D-2011)is gratefully acknowledged

Situational Awareness of Influenza Activity Based on Multiple Streams of Surveillance Data Using Multivariate Dynamic Linear Model

BACKGROUND: Multiple sources of influenza surveillance data are becoming more available; however integration of these data streams for situational awareness of influenza activity is less explored. METHODS AND RESULTS: We applied multivariate time-series methods to sentinel outpatient and school absenteeism surveillance data in Hong Kong during 2004-2009. School absenteeism data and outpatient surveillance data experienced interruptions due to school holidays and changes in public health guidelines during the pandemic, including school closures and the establishment of special designated flu clinics, which in turn provided 'drop-in' fever counts surveillance data. A multivariate dynamic linear model was used to monitor influenza activity throughout epidemics based on all available data. The inferred level followed influenza activity closely at different times, while the inferred trend was less competent with low influenza activity. Correlations between inferred level and trend from the multivariate model and reference influenza activity, measured by the product of weekly laboratory influenza detection rates and weekly general practitioner influenza-like illness consultation rates, were calculated and compared with those from univariate models. Over the whole study period, there was a significantly higher correlation (rho = 0.82, p</=0.02) for the inferred trend based on the multivariate model compared to other univariate models, while the inferred trend from the multivariate model performed as well as the best univariate model in the pre-pandemic and the pandemic period. The inferred trend and level from the multivariate model was able to match, if not outperform, the best univariate model albeit with missing data plus drop-in and drop-out of different surveillance data streams. An overall influenza index combining level and trend was constructed to demonstrate another potential use of the method. CONCLUSIONS: Our results demonstrate the potential use of multiple streams of influenza surveillance data to promote situational awareness about the level and trend of seasonal and pandemic influenza activity.published_or_final_versio

Status of Pandemic Influenza Vaccination and Factors Affecting It in Pregnant Women in Kahramanmaras, an Eastern Mediterranean City of Turkey

BACKGROUND: Pregnant women are a target group for receipt of influenza vaccine because there appears to be an elevated mortality and morbidity rate associated with influenza virus infection in pregnant women. The goal of this study is to determine the factors affecting the decisions of pregnant women in Turkey to be vaccinated or not for 2009 H1N1 influenza. METHODOLOGY: We enrolled 314 of 522 (60.2%) pregnant women who attended to the antenatal clinics of the Medical Faculty of Kahramanmaras Sutcuimam University's Department of Gynecology and Obstetrics between December 23, 2009, and February 1, 2010. We developed a 48-question survey which was completed in a face-to-face interview at the clinic with each pregnant woman. PRINCIPAL FINDINGS: Of the 314 pregnant women, 27.4% were in the first trimester, 33.8% were in the second trimester, and 38.8% were in the third trimester. Twenty-eight pregnant women (8.9%) got vaccinated. Of all the women interviewed, 68.5% stated that they were comfortable with their decisions about the vaccine, 7.3% stated they were not comfortable, and 24.2% stated that they were hesitant about their decisions. The probability of receiving the 2009 H1N1 vaccine was 3.46 times higher among working women than housewives, 1.85 times higher among women who have a child than those who do not, and 1.29 times higher among women with a high-school education or higher than those with only a secondary-school education and below. Correct knowledge about the minimal risks associated with receipt of influenza vaccine were associated with a significant increase in the probability of receiving the 2009 H1N1 vaccine. CONCLUSIONS/SIGNIFICANCE: The number of pregnant women in the study group who received the 2009 H1N1 vaccine was very low (8.9%) and two-thirds of them stated that they were comfortable with their decisions concerning the vaccine. Our results may have implications for public health measures to increase the currently low vaccination rate among pregnant women. Further studies are required to confirm whether our findings generalize to other influenza seasons and other settings

miR-132, an experience-dependent microRNA, is essential for visual cortex plasticity

Using quantitative analyses, we identified microRNAs (miRNAs) that were abundantly expressed in visual cortex and that responded to dark rearing and/or monocular deprivation. The most substantially altered miRNA, miR-132, was rapidly upregulated after eye opening and was delayed by dark rearing. In vivo inhibition of miR-132 in mice prevented ocular dominance plasticity in identified neurons following monocular deprivation and affected the maturation of dendritic spines, demonstrating its critical role in the plasticity of visual cortex circuits.National Eye Institute (Ruth L. Kirschstein Postdoctoral Fellowship 1F32EY020066-01)Simons Foundation (Postdoctoral Fellowship)National Institutes of Health (U.S.) (EY017098)National Institutes of Health (U.S.) (EY007023