Genetic Covariance Structure of Reading, Intelligence and Memory in Children

This study investigates the genetic relationship among reading performance, IQ, verbal and visuospatial working memory (WM) and short-term memory (STM) in a sample of 112, 9-year-old twin pairs and their older siblings. The relationship between reading performance and the other traits was explained by a common genetic factor for reading performance, IQ, WM and STM and a genetic factor that only influenced reading performance and verbal memory. Genetic variation explained 83% of the variation in reading performance; most of this genetic variance was explained by variation in IQ and memory performance. We hypothesize, based on these results, that children with reading problems possibly can be divided into three groups: (1) children low in IQ and with reading problems; (2) children with average IQ but a STM deficit and with reading problems; (3) children with low IQ and STM deficits; this group may experience more reading problems than the other two

Coupling models of cattle and farms with models of badgers for predicting the dynamics of bovine tuberculosis (TB)

Bovine TB is a major problem for the agricultural industry in several countries. TB can be contracted and spread by species other than cattle and this can cause a problem for disease control. In the UK and Ireland, badgers are a recognised reservoir of infection and there has been substantial discussion about potential control strategies. We present a coupling of individual based models of bovine TB in badgers and cattle, which aims to capture the key details of the natural history of the disease and of both species at approximately county scale. The model is spatially explicit it follows a very large number of cattle and badgers on a different grid size for each species and includes also winter housing. We show that the model can replicate the reported dynamics of both cattle and badger populations as well as the increasing prevalence of the disease in cattle. Parameter space used as input in simulations was swept out using Latin hypercube sampling and sensitivity analysis to model outputs was conducted using mixed effect models. By exploring a large and computationally intensive parameter space we show that of the available control strategies it is the frequency of TB testing and whether or not winter housing is practised that have the most significant effects on the number of infected cattle, with the effect of winter housing becoming stronger as farm size increases. Whether badgers were culled or not explained about 5%, while the accuracy of the test employed to detect infected cattle explained less than 3% of the variance in the number of infected cattle

Superior olivary complex organization and cytoarchitecture may be correlated with function and catarrhine primate phylogeny

In the mammalian auditory system, the medial nucleus of the trapezoid body and the lateral superior olive (MNTB-LSO system) contribute to binaural intensity processing and lateralization. Localization precision varies with the sound frequencies. As recency of common ancestry with human beings increases, primates have improved low-frequency sensitivity and reduced sensitivity to higher frequencies. The medial part of the MNTB is devoted to higher frequency processing. Thus, its high-frequency-dependent function is nearly lost in humans and its role in binaural processing as part of the contralateral pathway to the LSO remains questionable. Here, Nissl-stained sections of the superior olivary complex of man (Homo sapiens), bonobo (Pan paniscus), chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla), orangutan (Pongo pygmaeus), gibbon (Hylobates lar), and macaque (Macaca fascicularis) were compared to reveal differences and coincidences. From chimpanzees to humans, the size of the LSO decreased, and the MNTB as a compact nucleus nearly disappears. From chimpanzees to humans, the LSO/MNTB ratio increases dramatically too, whereas the LSO/MSO ratio remains 1.1; a finding that probably corresponds to the phylogenetic proximity between the species

Does dog-ownership influence seasonal patterns of neighbourhood-based walking among adults? A longitudinal study

<p>Abstract</p> <p>Background</p> <p>In general dog-owners are more physically active than non-owners, however; it is not known whether dog-ownership can influence seasonal fluctuations in physical activity. This study examines whether dog-ownership influences summer and winter patterns of neighbourhood-based walking among adults living in Calgary, Canada.</p> <p>Methods</p> <p>A cohort of adults, randomly sampled from the Calgary metropolitan area, completed postal surveys in winter and summer 2008. Both winter and summer versions of the survey included questions on dog-ownership, walking for recreation, and walking for transportation in residential neighbourhoods. <b>Participation </b>in neighbourhood-based walking was compared, among dog-owners and non-owners, and in summer and winter, using general linear modeling. <b>Stability </b>of participation in neighbourhood-based walking across summer and winter among dog-owners and non-owners was also assessed, using logistic regression.</p> <p>Results</p> <p>A total of 428 participants participated in the study, of whom 115 indicated owning dogs at the time of both surveys. Dog-owners reported more walking for recreation in their neighbourhoods than did non-owners, both in summer and in winter. Dog-owners were also more likely than non-owners to report participation in walking for recreation in their neighbourhoods, in summer as well as in winter. Dog-owners and non-owners did not differ in the amount of walking that they reported for transportation, either in summer or in winter.</p> <p>Conclusions</p> <p>By acting as cues for physical activity, dogs may help their owners remain active across seasons. Policies and programs related to dog-ownership and dog-walking, such as dog-supportive housing and dog-supportive parks, may assist in enhancing population health by promoting physical activity.</p

Ultra-porous titanium oxide scaffold with high compressive strength

Highly porous and well interconnected titanium dioxide (TiO2) scaffolds with compressive strength above 2.5 MPa were fabricated without compromising the desired pore architectural characteristics, such as high porosity, appropriate pore size, surface-to-volume ratio, and interconnectivity. Processing parameters and pore architectural characteristics were investigated in order to identify the key processing steps and morphological properties that contributed to the enhanced strength of the scaffolds. Cleaning of the TiO2 raw powder removed phosphates but introduced sodium into the powder, which was suggested to decrease the slurry stability. Strong correlation was found between compressive strength and both replication times and solid content in the ceramic slurry. Increase in the solid content resulted in more favourable sponge loading, which was achieved due to the more suitable rheological properties of the ceramic slurry. Repeated replication process induced only negligible changes in the pore architectural parameters indicating a reduced flaw size in the scaffold struts. The fabricated TiO2 scaffolds show great promise as load-bearing bone scaffolds for applications where moderate mechanical support is required

Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: A randomised cross-over trial

Objective: To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses. Design: Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period. Results: Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose. Conclusion: These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation

Individual and contextual covariates of burnout: a cross-sectional nationwide study of French teachers

<p>Abstract</p> <p>Background</p> <p>Limited information on the covariates of burnout syndrome in French teachers is available. The aim of this study was to evaluate the relative contributions of individual and contextual factors on the three burnout dimensions: emotional exhaustion, depersonalization, and reduced personal accomplishment.</p> <p>Methods</p> <p>The source data come from an epidemiological postal survey on physical and mental health conducted in 2005 among 20,099 education workers (in activity or retired) selected at random from the health plan records of the national education system. The response rate was 52.4%. Teachers in activity currently giving classes to students who participated in the survey (n = 3,940) were invited to complete a self-administered questionnaire including the Maslach Burnout Inventory. 2,558 teachers provided complete data (64.9%). Variables associated with high emotional exhaustion (highest quartile of score), high depersonalization (highest quartile), and reduced personal accomplishment (lowest quartile) were evaluated using multivariate logistic regression. Studied variables referred to demographic characteristics, socio-professional environment, job dissatisfaction, experienced difficulties at work, and teaching motivations.</p> <p>Results</p> <p>Different variables were associated with each burnout dimension. Female teachers were more susceptible to high emotional exhaustion and reduced personal accomplishment, whereas male teachers were more susceptible to high depersonalization. Elementary school teachers were more susceptible to high emotional exhaustion, but less susceptible to high depersonalization and reduced personal accomplishment than their higher school level counterparts. Experienced difficulties with pupils were associated with all three dimensions. A socio-economically underprivileged school neighbourhood was also related to high emotional exhaustion and high depersonalization.</p> <p>Conclusion</p> <p>Programs to enhance teaching environment might be an interesting approach to try to prevent burnout. It would be useful to take the different dimensions into account in planning the intervention.</p

PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma

Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma; DIPG), are uniformly fatal brain tumors that lack effective treatment. Analysis of CRISPR/Cas9 loss-of-function gene deletion screens identified PIK3CA and MTOR as targetable molecular dependencies across patient derived models of DIPG, highlighting the therapeutic potential of the blood-brain barrier–penetrant PI3K/Akt/mTOR inhibitor, paxalisib. At the human-equivalent maximum tolerated dose, mice treated with paxalisib experienced systemic glucose feedback and increased insulin levels commensurate with patients using PI3K inhibitors. To exploit genetic dependence and overcome resistance while maintaining compliance and therapeutic benefit, we combined paxalisib with the antihyperglycemic drug metformin. Metformin restored glucose homeostasis and decreased phosphorylation of the insulin receptor in vivo, a common mechanism of PI3K-inhibitor resistance, extending survival of orthotopic models. DIPG models treated with paxalisib increased calcium-activated PKC signaling. The brain penetrant PKC inhibitor enzastaurin, in combination with paxalisib, synergistically extended the survival of multiple orthotopic patient-derived and immunocompetent syngeneic allograft models; benefits potentiated in combination with metformin and standard-of-care radiotherapy. Therapeutic adaptation was assessed using spatial transcriptomics and ATAC-Seq, identifying changes in myelination and tumor immune microenvironment crosstalk. Collectively, this study has identified what we believe to be a clinically relevant DIPG therapeutic combinational strategy

Chronic fatigue syndrome: Harvey and Wessely's (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways

<p>Abstract</p> <p>Background</p> <p>In a recently published paper, Harvey and Wessely put forward a 'biopsychosocial' explanatory model for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is proposed to be applicable to (chronic) fatigue even when apparent medical causes are present.</p> <p>Methods</p> <p>Here, we review the model proposed by Harvey and Wessely, which is the rationale for behaviourally oriented interventions, such as cognitive behaviour therapy (CBT) and graded exercise therapy (GET), and compare this model with a biological model, in which inflammatory, immune, oxidative and nitrosative (IO&NS) pathways are key elements.</p> <p>Discussion</p> <p>Although human and animal studies have established that the pathophysiology of ME/CFS includes IO&NS pathways, these abnormalities are not included in the model proposed by Harvey and Wessely. Activation of IO&NS pathways is known to induce fatigue and somatic (F&S) symptoms and can be induced or maintained by viral and bacterial infections, physical and psychosocial stressors, or organic disorders such as (auto)immune disorders. Studies have shown that ME/CFS and major depression are both clinical manifestations of shared IO&NS pathways, and that both disorders can be discriminated by specific symptoms and unshared or differentiating pathways. Interventions with CBT/GET are potentially harmful for many patients with ME/CFS, since the underlying pathophysiological abnormalities may be intensified by physical stressors.</p> <p>Conclusions</p> <p>In contrast to Harvey and Wessely's (bio)psychosocial model for ME/CFS a bio(psychosocial) model based upon IO&NS abnormalities is likely more appropriate to this complex disorder. In clinical practice, we suggest physicians should also explore the IO&NS pathophysiology by applying laboratory tests that examine the pathways involved.</p

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty