Ambient Temperature and Biomarkers of Heart Failure: A Repeated Measures Analysis

Background: Extreme temperatures have been associated with hospitalization and death among individuals with heart failure, but few studies have explored the underlying mechanisms. Objectives: We hypothesized that outdoor temperature in the Boston, Massachusetts, area (1- to 4-day moving averages) would be associated with higher levels of biomarkers of inflammation and myocyte injury in a repeated-measures study of individuals with stable heart failure. Methods: We analyzed data from a completed clinical trial that randomized 100 patients to 12 weeks of tai chi classes or to time-matched education control. B-type natriuretic peptide (BNP), C-reactive protein (CRP), and tumor necrosis factor (TNF) were measured at baseline, 6 weeks, and 12 weeks. Endothelin-1 was measured at baseline and 12 weeks. We used fixed effects models to evaluate associations with measures of temperature that were adjusted for time-varying covariates. Results: Higher apparent temperature was associated with higher levels of BNP beginning with 2-day moving averages and reached statistical significance for 3- and 4-day moving averages. CRP results followed a similar pattern but were delayed by 1 day. A 5°C change in 3- and 4-day moving averages of apparent temperature was associated with 11.3% [95% confidence interval (CI): 1.1, 22.5; :p = 0.03) and 11.4% (95% CI: 1.2, 22.5; p = 0.03) higher BNP. A 5°C change in the 4-day moving average of apparent temperature was associated with 21.6% (95% CI: 2.5, 44.2; p = 0.03) higher CRP. No clear associations with TNF or endothelin-1 were observed. Conclusions: Among patients undergoing treatment for heart failure, we observed positive associations between temperature and both BNP and CRP—predictors of heart failure prognosis and severity

Measles virus causes immunogenic cell death in human melanoma

Oncolytic viruses (OV) are promising treatments for cancer, with several currently undergoing testing in randomised clinical trials. Measles virus (MV) has not yet been tested in models of human melanoma. This study demonstrates the efficacy of MV against human melanoma. It is increasingly recognised that an essential component of therapy with OV is the recruitment of host anti-tumour immune responses, both innate and adaptive. MV-mediated melanoma cell death is an inflammatory process, causing the release of inflammatory cytokines including type-1 interferons and the potent danger signal HMGB1. Here, using human in vitro models, we demonstrate that MV enhances innate antitumour activity, and that MV-mediated melanoma cell death is capable of stimulating a melanoma-specific adaptive immune response

Recurrent Selection to Alter Grain Methionine Concentration and Improve Nutritional Value of Maize

Methionine is an essential amino acid that is limiting in maize- (Zea mays L.) based diets. The objective of this work was to determine whether we could alter grain methionine concentration in random-mated maize populations by mass selection for methionine concentration using a microbial assay. In one study, we developed two populations by selecting for high or low methionine concentration (HM or LM, respectively) for three generations starting from the random-mated population BS11. Grain from these populations was used to formulate diets for a feeding trial in which 15 rats were fed HM grain and 15 rats were fed LM grain. Rats on the HM diet had a 0.018 higher feed efficiency (g gain/g feed) than rats on the LM diet. In a second study, we performed three cycles of selection for high or low methionine concentration starting with two random-mated populations, BS11 and BS31. We evaluated each cycle of selection in a field trial with two replications in each of two years. Methionine concentration was significantly correlated with the cycle of selection, changing on average 0.004 g methionine/100 g grain per cycle. Kernel mass, %N, oil, protein, starch, tryptophan, and lysine concentration did not exhibit significant correlations with cycle of selection. We conclude that recurrent selection for grain methionine concentration using a microbial assay is an effective method to alter methionine content

Handedness for Unimanual Grasping in 564 Great Apes: The Effect on Grip Morphology and a Comparison with Hand Use for a Bimanual Coordinated Task

A number of factors have been proposed to influence within and between species variation in handedness in non-human primates. In the initial study, we assessed the influence of grip morphology on hand use for simple reaching in a sample of 564 great apes including 49 orangutans Pongo pygmaeus, 66 gorillas Gorilla gorilla, 354 chimpanzees Pan troglodytes and 95 bonobos Pan paniscus. Overall, we found a significant right hand bias for reaching. We also found a significant effect of the grip morphology of hand use. Grasping with the thumb and index finger was more prevalent in the right compared to left hand in all four species. There was no significant sex effect on the patterns of handedness. In a subsample of apes, we also compared consistency in hand use for simple reaching with previously published data on a task that measures handedness for bimanual actions. We found that the ratio of subjects with consistent right compared to left hand use was more prevalent in bonobos, chimpanzees and gorillas but not orangutans. However, for all species, the proportion of subjects with inconsistent hand preferences between the tasks was relatively high suggesting some measures may be more sensitive in assessing handedness than others

Seasonal Arctic sea ice forecasting with probabilistic deep learning.

Anthropogenic warming has led to an unprecedented year-round reduction in Arctic sea ice extent. This has far-reaching consequences for indigenous and local communities, polar ecosystems, and global climate, motivating the need for accurate seasonal sea ice forecasts. While physics-based dynamical models can successfully forecast sea ice concentration several weeks ahead, they struggle to outperform simple statistical benchmarks at longer lead times. We present a probabilistic, deep learning sea ice forecasting system, IceNet. The system has been trained on climate simulations and observational data to forecast the next 6 months of monthly-averaged sea ice concentration maps. We show that IceNet advances the range of accurate sea ice forecasts, outperforming a state-of-the-art dynamical model in seasonal forecasts of summer sea ice, particularly for extreme sea ice events. This step-change in sea ice forecasting ability brings us closer to conservation tools that mitigate risks associated with rapid sea ice loss

Evaluating the theory of executive dysfunction in autism

In this paper studies of executive function in autism spectrum disorder are reviewed. Executive function is an umbrella term for functions such as planning, working memory, impulse control, inhibition, and shifting set, as well as for the initiation and monitoring of action. In this review, the focus will be on planning, inhibition, shifting set, generativity, and action monitoring. While it is known that these functions depend upon the frontal lobes, and particularly on prefrontal cortex, very little is known about neuroanatomical correlates of executive function in autism. The review acknowledges the complexity of investigating executive functions in autism, the possible influence of IQ on executive performance in these groups and the possibility of overlap between performance on tests of executive function in other neurodevelopmental disorders that are likely to involve congenital deficits in the frontal lobes, such as attention deficit hyperactivity disorder and Tourette's syndrome

Gender differences in the impact of population-level alcohol policy interventions: evidence synthesis of systematic reviews

Background: Consistent review-level evidence supports the effectiveness of population-level alcohol policies in reducing alcohol-related harms. Such policies interact with well-established social, cultural and biological differences in how men and women perceive, relate to and use alcohol, and with wider inequalities, in ways which may give rise to gender differences in policy effectiveness.  Aims: To examine the extent to which gender-specific data and analyses were considered in, and are available from, systematic reviews of population-level alcohol policy interventions, and where possible, to conduct a narrative synthesis of relevant data.  Methods: A prior systematic ‘review of reviews’ of population level alcohol interventions 2002-2012 was updated to May 2014, all gender-relevant data extracted, and the level and quality of gender reporting assessed. A narrative synthesis of extracted findings was conducted.  Results: Sixty-three systematic reviews, covering ten policy areas, were included. Five reviews (8%) consistently provided information on baseline participation by gender for each individual study in the review and twenty-nine (46%) reported some gender-specific information on the impact of the policies under consideration. Specific findings include evidence of possible gender differences in the impact of and exposure to alcohol marketing, and a failure to consider potential unintended consequences and harm to others in most reviews.  Conclusions: Gender is poorly reported in systematic reviews of population-level interventions to reduce alcohol-related harm, hindering assessment of the intended and unintended effects of such policies on women and men

Support surfaces for pressure ulcer prevention.

BACKGROUND: Pressure ulcers (also known as bedsores, pressure sores, decubitus ulcers) are areas of localised damage to the skin and underlying tissue due to pressure, shear or friction. They are common in the elderly and immobile and costly in financial and human terms. Pressure-relieving beds, mattresses and seat cushions are widely used as aids to prevention in both institutional and non-institutional settings. OBJECTIVES: This systematic review seeks to answer the following questions: to what extent do pressure-relieving cushions, beds, mattress overlays and mattress replacements reduce the incidence of pressure ulcers compared with standard support surfaces? how effective are different pressure-relieving surfaces in preventing pressure ulcers, compared to one another? SEARCH STRATEGY: The Specialised Trials Register of the Cochrane Wounds Group (compiled from regular searches of many electronic databases including MEDLINE, CINAHL and EMBASE plus handsearching of specialist journals and conference proceedings) was searched up to January 2004, Issue 3, 2004 of the Cochrane Central Register of Controlled Trials was also searched. The reference sections of included studies were searched for further trials. SELECTION CRITERIA: Randomised controlled trials (RCTs), published or unpublished, which assessed the effectiveness of beds, mattresses, mattress overlays, and seating cushions for the prevention of pressure ulcers, in any patient group, in any setting. RCTs were eligible for inclusion if they reported an objective, clinical outcome measure such as incidence and severity of new of pressure ulcers developed. Studies which only reported proxy outcome measures such as interface pressure were excluded. DATA COLLECTION AND ANALYSIS: Trial data were extracted by one researcher and checked by a second. The results from each study are presented as relative risk for dichotomous variables. Where deemed appropriate, similar studies were pooled in a meta analysis. MAIN RESULTS: 41 RCTs were included in the review. Foam alternatives to the standard hospital foam mattress can reduce the incidence of pressure ulcers in people at risk. The relative merits of alternating and constant low pressure devices, and of the different alternating pressure devices for pressure ulcer prevention are unclear.Pressure-relieving overlays on the operating table have been shown to reduce postoperative pressure ulcer incidence, although one study indicated that an overlay resulted in adverse skin changes. One trial indicated that Australian standard medical sheepskins prevented pressure ulcers. There is insufficient evidence to draw conclusions on the value of seat cushions, limb protectors and various constant low pressure devices as pressure ulcer prevention strategies.A study of Accident & Emergency trolley overlays did not identify a reduction in pressure ulcer incidence. There are tentative indications that foot waffle heel elevators, a particular low air loss hydrotherapy mattress and an operating theatre overlay are harmful. REVIEWERS' CONCLUSIONS: In people at high risk of pressure ulcer development, consideration should be given to the use of higher specification foam mattresses rather than standard hospital foam mattresses. The relative merits of higher-tech constant low pressure and alternating pressure for prevention are unclear. Organisations might consider the use of pressure relief for high risk patients in the operating theatre, as this is associated with a reduction in post-operative incidence of pressure ulcers. Seat cushions and overlays designed for use in Accident & Emergency settings have not been adequately evaluated

Spatial Dimensions of Dengue Virus Transmission across Interepidemic and Epidemic Periods in Iquitos, Peru (1999–2003)

To target prevention and control strategies for dengue fever, it is essential to understand how the virus travels through the city. We report spatial analyses of dengue infections from a study monitoring school children and adult family members for dengue infection at six-month intervals from 1999–2003, in the Amazonian city of Iquitos, Peru. At the beginning of the study, only DENV serotypes 1 and 2 were circulating. Clusters of infections of these two viruses were concentrated in the northern region of the city, where mosquito indices and previous DENV infection were both high. In 2002, DENV-3 invaded the city, replacing DENV-1 and -2 as the dominant strain. During the invasion process, the virus spread rapidly across the city, at low levels. After this initial phase, clusters of infection appeared first in the northern region of the city, where clusters of DENV-1 and DENV-2 had occurred in prior years. Most of the clusters we identified had radii >100 meters, indicating that targeted or reactive treatment of these high-risk areas might be an effective proactive intervention strategy. Our results also help explain why vector control within 100 m of a dengue case is often not successful for large-scale disease prevention