Accelerating exhaustive pairwise metagenomic comparisons

In this manuscript, we present an optimized and parallel version of our previous work IMSAME, an exhaustive gapped aligner for the pairwise and accurate comparison of metagenomes. Parallelization strategies are applied to take advantage of modern multiprocessor architectures. In addition, sequential optimizations in CPU time and memory consumption are provided. These algorithmic and computational enhancements enable IMSAME to calculate near optimal alignments which are used to directly assess similarity between metagenomes without requiring reference databases. We show that the overall efficiency of the parallel implementation is superior to 80% while retaining scalability as the number of parallel cores used increases. Moreover, we also show thats equential optimizations yield up to 8x speedup for scenarios with larger data.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Insulin clearance and the incidence of type 2 diabetes in Hispanics and African Americans: the IRAS Family Study.

ObjectiveWe aimed to identify factors that are independently associated with the metabolic clearance rate of insulin (MCRI) and to examine the association of MCRI with incident type 2 diabetes in nondiabetic Hispanics and African Americans.Research design and methodsWe investigated 1,116 participants in the Insulin Resistance Atherosclerosis Study (IRAS) Family Study with baseline examinations from 2000 to 2002 and follow-up examinations from 2005 to 2006. Insulin sensitivity (S(I)), acute insulin response (AIR), and MCRI were determined at baseline from frequently sampled intravenous glucose tolerance tests. MCRI was calculated as the ratio of the insulin dose over the incremental area under the curve of insulin. Incident diabetes was defined as fasting glucose ≥126 mg/dL or antidiabetic medication use by self-report.ResultsWe observed that S(I) and HDL cholesterol were independent positive correlates of MCRI, whereas fasting insulin, fasting glucose, subcutaneous adipose tissue, visceral adipose tissue, and AIR were independent negative correlates (all P < 0.05) at baseline. After 5 years of follow-up, 71 (6.4%) participants developed type 2 diabetes. Lower MCRI was associated with a higher risk of incident diabetes after adjusting for demographics, lifestyle factors, HDL cholesterol, indexes of obesity and adiposity, and insulin secretion (odds ratio 2.01 [95% CI 1.30-3.10], P = 0.0064, per one-SD decrease in loge-transformed MCRI).ConclusionsOur data showed that lower MCRI predicts the incidence of type 2 diabetes

The impact of COVID-19 on anxiety and wellbeing for families of individuals with Special Education Needs and Disabilities in the UK

COVID-19 has affected people across the world. However, it has been suggested that individuals with Special Education Needs and Disabilities (SEND) and their families might have been particularly impacted by the first national lockdown in the UK. In contrast to previous studies, the current study examined wellbeing and anxiety at different time points and included a control group matched for family situation. Parents of 402 individuals with SEND reported on their own anxiety and wellbeing as well as that of their son/daughter at three time points (before COVID-19, when COVID-19 pandemic started, and during the national lockdown). In addition, data from 186 typically developing (TD) siblings was obtained. Repeated measures ANOVAs and regression analyses showed that, although both individuals with SEND and their TD siblings showed increased anxiety across the three time points, levels of anxiety were not predicted by age, gender or health. Instead, levels of anxiety in the SEND group, but not the TD siblings, were predicted by awareness about COVID-19, diagnosis of an existing anxiety disorder as well as parental anxiety. In addition, whilst TD individuals were reported to increasingly worry about social related issues as well as family related issues, those with SEND were reported to worry about issues related to school closures. These findings show that COVID-19 impacts the wellbeing of those with SEND differently to that of their TD siblings and that school closures have a particular effect on this group. Further implications for policy impact and interventions are discussed

The influence of particle surface roughness on elastic stiffness and dynamic response

Discrete-element method (DEM) simulations of planar wave propagation are used to examine the effect of particle surface roughness on the stiffness and dynamic response of granular materials. A new contact model that considers particle surface roughness is implemented in the DEM simulations. Face-centred cubic lattice packings and random configurations are used; uniform spheres are considered in both cases to isolate fabric and contact model effects from inertia effects. For the range of values considered here surface roughness caused a significant reduction in stiffness, particularly at lower confining stresses. The simulations confirm that surface roughness effects can at least partially explain the value of the exponent in the relationship between stiffness and mean confining stress for an assembly of spherical particles. Frequency domain analyses showed that the maximum frequency transmitted through the sample is reduced when surface roughness is considered. The assumption of homogeneity of stress and contacts in analytical micromechanical models is shown to lead to an overestimation of stiffness

Mindfulness meditation in the treatment of substance use disorders and preventing future relapse: neurocognitive mechanisms and clinical implications

Substance use disorders (SUDs) are a pervasive public health problem with deleterious consequences for individuals, families, and society. Furthermore, SUD intervention is complicated by the continuous possibility of relapse. Despite decades of research, SUD relapse rates remain high, underscoring the need for more effective treatments. Scientific findings indicate that SUDs are driven by dysregulation of neural processes underlying reward learning and executive functioning. Emerging evidence suggests that mindfulness training can target these neurocognitive mechanisms to produce significant therapeutic effects on SUDs and prevent relapse. The purpose of this manuscript is to review the cognitive, affective, and neural mechanisms underlying the effects of mindfulness-based interventions (MBIs) on SUDs. We discuss the etiology of addiction and neurocognitive processes related to the development and maintenance of SUDs. We then explore evidence supporting use of MBIs for intervening in SUDs and preventing relapse. Finally, we provide clinical recommendations about how these therapeutic mechanisms might be applied to intervening in SUDs and preventing relapse.National Institute of Health (NIH) award to ELG (R01DA042033

The use of disaggregated demand information to improve forecasts and stock allocation during sales promotions: a simulation and optimisation study using supermarket loyalty card data

Our work highlights the importance of using disaggregated demand information at store level to improve sales forecasts and stock allocation during sales promotions. Monte Carlo simulation and optimisation modelling were used to estimate short-term promotional impacts. Supermarket loyalty card data was used from a major UK retailer to identify the benefits of using disaggregated demand data for improved forecasting and stock allocation. The results suggest that there is a high degree of heterogeneity in demand at individual store level due to number of factors including the weather, the characteristics of shoppers, the characteristics of products and store format, all of which conspire to generate significant variation in promotional uplifts. The paper is the first to use supermarket loyalty card data to generate store level promotional forecasts and quantify the benefits of disaggregating the allocation of promotional stock to the level of individual stores rather than regional distribution centres

Toxicogenomic analysis incorporating operon-transcriptional coupling and toxicant concentration-expression response: analysis of MX-treated Salmonella

<p>Abstract</p> <p>Background</p> <p>Deficiencies in microarray technology cause unwanted variation in the hybridization signal, obscuring the true measurements of intracellular transcript levels. Here we describe a general method that can improve microarray analysis of toxicant-exposed cells that uses the intrinsic power of transcriptional coupling and toxicant concentration-expression response data. To illustrate this approach, we characterized changes in global gene expression induced in <it>Salmonella typhimurium </it>TA100 by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(<it>5H</it>)-furanone (MX), the primary mutagen in chlorinated drinking water. We used the co-expression of genes within an operon and the monotonic increases or decreases in gene expression relative to increasing toxicant concentration to augment our identification of differentially expressed genes beyond Bayesian-t analysis.</p> <p>Results</p> <p>Operon analysis increased the number of altered genes by 95% from the list identified by a Bayesian t-test of control to the highest concentration of MX. Monotonic analysis added 46% more genes. A functional analysis of the resulting 448 differentially expressed genes yielded functional changes beyond what would be expected from only the mutagenic properties of MX. In addition to gene-expression changes in DNA-damage response, MX induced changes in expression of genes involved in membrane transport and porphyrin metabolism, among other biological processes. The disruption of porphyrin metabolism might be attributable to the structural similarity of MX, which is a chlorinated furanone, to ligands indigenous to the porphyrin metabolism pathway. Interestingly, our results indicate that the <it>lexA </it>regulon in <it>Salmonella</it>, which partially mediates the response to DNA damage, may contain only 60% of the genes present in this regulon in <it>E. coli</it>. In addition, <it>nanH </it>was found to be highly induced by MX and contains a putative <it>lexA </it>regulatory motif in its regulatory region, suggesting that it may be regulated by <it>lexA</it>.</p> <p>Conclusion</p> <p>Operon and monotonic analyses improved the determination of differentially expressed genes beyond that of Bayesian-t analysis, showing that MX alters cellular metabolism involving pathways other than DNA damage. Because co-expression of similarly functioning genes also occurs in eukaryotes, this method has general applicability for improving analysis of toxicogenomic data.</p

Malaria parasite interactions with the human host

The interaction between the malaria parasite and the human host involves a number of interactions that result in the parasite evading the human immune system. Since the stages of the malaria lifecycle are complex, this allows the use of various immune evasion strategies by the malaria parasite and has major implications in the development of a vaccine for malaria endemic areas. The present review highlights key host:parasite interactions. Plasmodia puts selection pressure on human gene frequencies, and studies into host genetic factors such as the Duffy blood group and sickle cell anaemia offer insight into the host- parasite relationship. In addition, parasite interactions with the different effector arms of the immune system can result in altered peptide ligand (APL) antagonism which alters the immune response from a pro- to an anti-inflammatory T cell response. Recent insights into the interaction between professional antigen presenting cells, dendritic cells (DCs), and malaria parasites is discussed in detail