The strong weak convergence of the quasi-EA

In this paper, we investigate the convergence of a novel simulation scheme to the target diffusion process. This scheme, the Quasi-EA, is closely related to the Exact Algorithm (EA) for diffusion processes, as it is obtained by neglecting the rejection step in EA. We prove the existence of a myopic coupling between the Quasi-EA and the diffusion. Moreover, an upper bound for the coupling probability is given. Consequently we establish the convergence of the Quasi-EA to the diffusion with respect to the total variation distance

High frequency temperature variability reduces the risk of coral bleaching

Coral bleaching is the detrimental expulsion of algal symbionts from their cnidarian hosts, and predominantly occurs when corals are exposed to thermal stress. The incidence and severity of bleaching is often spatially heterogeneous within reef-scales (<1 km), and is therefore not predictable using conventional remote sensing products. Here, we systematically assess the relationship between in situ measurements of 20 environmental variables, along with seven remotely sensed SST thermal stress metrics, and 81 observed bleaching events at coral reef locations spanning five major reef regions globally. We find that high-frequency temperature variability (i.e., daily temperature range) was the most influential factor in predicting bleaching prevalence and had a mitigating effect, such that a 1 °C increase in daily temperature range would reduce the odds of more severe bleaching by a factor of 33. Our findings suggest that reefs with greater high-frequency temperature variability may represent particularly important opportunities to conserve coral ecosystems against the major threat posed by warming ocean temperatures

E-cadherin and cell adhesion: a role in architecture and function in the pancreatic islet

Background/Aims: The efficient secretion of insulin from beta-cells requires extensive intra-islet communication. The cell surface adhesion protein epithelial (E)-cadherin (ECAD) establishes and maintains epithelial tissues such as the islets of Langerhans. In this study, the role of ECAD in regulating insulin secretion from pseudoislets was investigated. Methods: The effect of an immuno-neutralising ECAD on gross morphology, cytosolic calcium signalling, direct cell-to-cell communication and insulin secretion was assessed by fura-2 microfluorimetry, Lucifer Yellow dye injection and insulin ELISA in an insulin-secreting model system. Results: Antibody blockade of ECAD reduces glucose-evoked changes in [Ca2+](i) and insulin secretion. Neutralisation of ECAD causes a breakdown in the glucose-stimulated synchronicity of calcium oscillations between discrete regions within the pseudoislet, and the transfer of dye from an individual cell within a cell cluster is attenuated in the absence of ECAD ligation, demonstrating that gap junction communication is disrupted. The functional consequence of neutralising ECAD is a significant reduction in insulin secretion. Conclusion: Cell adhesion via ECAD has distinct roles in the regulation of intercellular communication between beta-cells within islets, with potential repercussions for insulin secretion. Copyright (C) 2007 S. Karger AG, Basel

From field to plate: How do bacterial enteric pathogens interact with ready-to-eat fruit and vegetables, causing disease outbreaks?

Ready-to-eat fruit and vegetables are a convenient source of nutrients and fibre for consumers, and are generally safe to eat, but are vulnerable to contamination with human enteric bacterial pathogens. Over the last decade, Salmonella spp., pathogenic Escherichia coli, and Listeria monocytogenes have been linked to most of the bacterial outbreaks of foodborne illness associated with fresh produce. The origins of these outbreaks have been traced to multiple sources of contamination from pre-harvest (soil, seeds, irrigation water, domestic and wild animal faecal matter) or post-harvest operations (storage, preparation and packaging). These pathogens have developed multiple processes for successful attachment, survival and colonization conferring them the ability to adapt to multiple environments. However, these processes differ across bacterial strains from the same species, and across different plant species or cultivars. In a competitive environment, additional risk factors are the plant microbiome phyllosphere and the plant responses; both factors directly modulate the survival of the pathogens on the leaf's surface. Understanding the mechanisms involved in bacterial attachment to, colonization of, and proliferation, on fresh produce and the role of the plant in resisting bacterial contamination is therefore crucial to reducing future outbreaks

From laboratory to industrial storage - Translating volatile organic compounds into markers for assessing garlic storage quality

Garlic (Allium sativum L.) has long been grown for its culinary and health-promoting qualities. The seasonal nature of garlic cropping requires that bulbs be stored for many months after harvest to ensure a year-round supply. During this time, quality is known to deteriorate, and efforts have been made to improve the longevity of stored bulbs. Cold temperatures within the stores prolong shelf life, but fine temperature control is needed to avoid freezing damage or cold induced stress. Here, quality traits (alliinase activity, firmness, and water content) are measured in response to a 96 h − 5 °C cold stress, to simulate the effect of non-isothermic temperature control in a − 1.5 °C warehouse. Volatile organic compounds (VOCs) are measured by thermal desorption gas chromatography time of flight mass spectrometry to identify markers of non-isothermic storage in garlic. 129 compounds were putatively identified and four (L-lactic acid, 2,6-dimethylhetpadecane, 4-methyldodecane, and methylcyclopentane) showed high predictive accuracy for cold stress. VOCs were also sampled directly from a cold storage facility and the whole profile discriminated between sampling time points. Five VOCS were highly predictive for storage time in the warehouse but were different to VOCs previously shown to discriminate between storage times in a laboratory setting. This indicates the need for realistic warehouse experiments to test quality markers

The determinants of food choice

Health nudge interventions to steer people into healthier lifestyles are increasingly applied by governments worldwide, and it is natural to look to such approaches to improve health by altering what people choose to eat. However, to produce policy recommendations that are likely to be effective, we need to be able to make valid predictions about the consequences of proposed interventions, and for this, we need a better understanding of the determinants of food choice. These determinants include dietary components (e.g. highly palatable foods and alcohol), but also diverse cultural and social pressures, cognitive-affective factors (perceived stress, health attitude, anxiety and depression), and familial, genetic and epigenetic influences on personality characteristics. In addition, our choices are influenced by an array of physiological mechanisms, including signals to the brain from the gastrointestinal tract and adipose tissue, which affect not only our hunger and satiety but also our motivation to eat particular nutrients, and the reward we experience from eating. Thus, to develop the evidence base necessary for effective policies, we need to build bridges across different levels of knowledge and understanding. This requires experimental models that can fill in the gaps in our understanding that are needed to inform policy, translational models that connect mechanistic understanding from laboratory studies to the real life human condition, and formal models that encapsulate scientific knowledge from diverse disciplines, and which embed understanding in a way that enables policy-relevant predictions to be made. Here we review recent developments in these areas.</p

Risks of breast or ovarian cancer in BRCA1 or BRCA2 predictive test negatives: findings from the EMBRACE study.

Purpose BRCA1/BRCA2 predictive test negatives are proven noncarriers of a BRCA1/BRCA2 mutation that is carried by their relatives. The risk of developing breast cancer (BC) or epithelial ovarian cancer (EOC) in these women is uncertain. The study aimed to estimate risks of invasive BC and EOC in a large cohort of BRCA1/BRCA2 predictive test negatives. Methods We used cohort analysis to estimate incidences, cumulative risks, and standardized incidence ratios (SIRs). Results A total of 1,895 unaffected women were eligible for inclusion in the BC risk analysis and 1,736 in the EOC risk analysis. There were 23 incident invasive BCs and 2 EOCs. The cumulative risk of invasive BC was 9.4% (95% confidence interval (CI) 5.9-15%) by age 85 years and the corresponding risk of EOC was 0.6% (95% CI 0.2-2.6%). The SIR for invasive BC was 0.93 (95% CI 0.62-1.40) in the overall cohort, 0.85 (95% CI 0.48-1.50) in noncarriers from BRCA1 families, and 1.03 (95% CI 0.57-1.87) in noncarriers from BRCA2 families. The SIR for EOC was 0.79 (95% CI 0.20-3.17) in the overall cohort. Conclusion Our results did not provide evidence for elevated risks of invasive BC or EOC in BRCA1/BRCA2 predictive test negatives. Genetics in Medicine advance online publication, 22 March 2018; doi:10.1038/gim.2018.44

Treating the placenta to prevent adverse effects of gestational hypoxia on fetal brain development.

Some neuropsychiatric disease, including schizophrenia, may originate during prenatal development, following periods of gestational hypoxia and placental oxidative stress. Here we investigated if gestational hypoxia promotes damaging secretions from the placenta that affect fetal development and whether a mitochondria-targeted antioxidant MitoQ might prevent this. Gestational hypoxia caused low birth-weight and changes in young adult offspring brain, mimicking those in human neuropsychiatric disease. Exposure of cultured neurons to fetal plasma or to secretions from the placenta or from model trophoblast barriers that had been exposed to altered oxygenation caused similar morphological changes. The secretions and plasma contained altered microRNAs whose targets were linked with changes in gene expression in the fetal brain and with human schizophrenia loci. Molecular and morphological changes in vivo and in vitro were prevented by a single dose of MitoQ bound to nanoparticles, which were shown to localise and prevent oxidative stress in the placenta but not in the fetus. We suggest the possibility of developing preventative treatments that target the placenta and not the fetus to reduce risk of psychiatric disease in later life

Prostate Cancer Risk by BRCA2 Genomic Regions.

A BRCA2 prostate cancer cluster region (PCCR) was recently proposed (c.7914 to 3') wherein pathogenic variants (PVs) are associated with higher prostate cancer (PCa) risk than PVs elsewhere in the BRCA2 gene. Using a prospective cohort study of 447 male BRCA2 PV carriers recruited in the UK and Ireland from 1998 to 2016, we estimated standardised incidence ratios (SIRs) compared with population incidences and assessed variation in risk by PV location. Carriers of PVs in the PCCR had a PCa SIR of 8.33 (95% confidence interval [CI] 4.46-15.6) and were at a higher risk of PCa than carriers of other BRCA2 PVs (SIR = 3.31, 95% CI 1.97-5.57; hazard ratio = 2.34, 95% CI 1.09-5.03). PCCR PV carriers had an estimated cumulative PCa risk of 44% (95% CI 23-72%) by the age of 75 yr and 78% (95% CI 54-94%) by the age of 85 yr. Our results corroborate the existence of a PCCR in BRCA2 in a prospective cohort. PATIENT SUMMARY: In this report, we investigated whether the risk of prostate cancer for men with a harmful mutation in the BRCA2 gene differs based on where in the gene the mutation is located. We found that men with mutations in one region of BRCA2 had a higher risk of prostate cancer than men with mutations elsewhere in the gene