Analysis of bolted flanged panel joint for GRP sectional tanks

Peer reviewedPublisher PD

A missense TGFB2 variant p.(Arg320Cys) causes a paradoxical and striking increase in aortic TGFB1/2 expression.

Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder with a range of cardiovascular, skeletal, craniofacial and cutaneous manifestations. LDS type 4 is caused by mutations in TGFβ ligand 2 (TGFB2) and based on the family pedigrees described to date, appears to have a milder clinical phenotype, often presenting with isolated aortic disease. We sought to investigate its molecular basis in a new pedigree. We identified a missense variant p.(Arg320Cys) (NM_003238.3) in a highly evolutionary conserved region of TGFB2 in a new LDS type 4 pedigree with multiple cases of aortic aneurysms and dissections. There was striking upregulation of TGFB1 and TGFB2 expression on immunofluorescent staining, and western blotting of the aortic tissue from the index case confirming the functional importance of the variant. This case highlights the striking paradox of predicted loss-of-function mutations in TGFB2 causing enhanced TGFβ signaling in this emerging familial aortopathy.Raya Al Maskari has a PhD studentship funded by the Omani government.This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/ejhg.2016.14

Multisensory information facilitates reaction speed by enlarging activity difference between superior colliculus hemispheres in rats

Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement activity of another population of neurons decreased with faster reaction speed for the ipsiversive movement. When visual and auditory stimuli were presented simultaneously, the premovement activity of a population of neurons for the contraversive movement was enhanced, whereas the premovement activity of another population of neurons for the ipsiversive movement was depressed. Unilateral inactivation of SC using muscimol prolonged reaction times of contraversive movements, but it shortened those of ipsiversive movements. These findings suggest that the difference in activity between the SC hemispheres regulates the reaction speed of motor responses, and multisensory information enlarges the activity difference resulting in faster responses

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

Cognitive Effects of Risperidone in Children with Autism and Irritable Behavior

Objective: The objective of this research was to explore the effects of risperidone on cognitive processes in children with autism and irritable behavior. Method: Thirty-eight children, ages 5-17 years with autism and severe behavioral disturbance, were randomly assigned to risperidone (0.5 to 3.5 mg/day) or placebo for 8 weeks. This sample of 38 was a subset of 101 subjects who participated in the clinical trial; 63 were unable to perform the cognitive tasks. A double-blind placebo-controlled parallel groups design was used. Dependent measures included tests of sustained attention, verbal learning, hand-eye coordination, and spatial memory assessed before, during, and after the 8-week treatment. Changes in performance were compared by repeated measures ANOVA. Results: Twenty-nine boys and 9 girls with autism and severe behavioral disturbance and a mental age ≥18 months completed the cognitive part of the study. No decline in performance occurred with risperidone. Performance on a cancellation task (number of correct detections) and a verbal learning task (word recognition) was better on risperidone than on placebo (without correction for multiplicity). Equivocal improvement also occurred on a spatial memory task. There were no significant differences between treatment conditions on the Purdue Pegboard (hand-eye coordination) task or the Analog Classroom Task (timed math test). Conclusion: Risperidone given to children with autism at doses up to 3.5 mg for up to 8 weeks appears to have no detrimental effect on cognitive performance

Effect of parasympathetic stimulation on brain activity during appraisal of fearful expressions

Autonomic nervous system activity is an important component of human emotion. Mental processes influence bodily physiology, which in turn feeds back to influence thoughts and feelings. Afferent cardiovascular signals from arterial baroreceptors in the carotid sinuses are processed within the brain and contribute to this two-way communication with the body. These carotid baroreceptors can be stimulated non-invasively by externally applying focal negative pressure bilaterally to the neck. In an experiment combining functional neuroimaging (fMRI) with carotid stimulation in healthy participants, we tested the hypothesis that manipulating afferent cardiovascular signals alters the central processing of emotional information (fearful and neutral facial expressions). Carotid stimulation, compared with sham stimulation, broadly attenuated activity across cortical and brainstem regions. Modulation of emotional processing was apparent as a significant expression-by-stimulation interaction within left amygdala, where responses during appraisal of fearful faces were selectively reduced by carotid stimulation. Moreover, activity reductions within insula, amygdala, and hippocampus correlated with the degree of stimulation-evoked change in the explicit emotional ratings of fearful faces. Across participants, individual differences in autonomic state (heart rate variability, a proxy measure of autonomic balance toward parasympathetic activity) predicted the extent to which carotid stimulation influenced neural (amygdala) responses during appraisal and subjective rating of fearful faces. Together our results provide mechanistic insight into the visceral component of emotion by identifying the neural substrates mediating cardiovascular influences on the processing of fear signals, potentially implicating central baroreflex mechanisms for anxiolytic treatment targets

Are mammography image acquisition factors, compression pressure and paddle tilt, associated with breast cancer detection in screening?

Objectives: To assess the associations between objectively measured mammographic compression pressure and paddle tilt and breast cancer (BC) detected at the same (“contemporaneous”) screen, subsequent screens, or in-between screens (interval cancers). Methods: Automated pressure and paddle tilt estimates were derived for 80,495 mammographic examina-tions in a UK population-based screening programme. Adjusted logistic regression models were fitted to estimate the associations of compression parameters with BC detected at contemporaneous screen (777 cases). Nested case-control designs were used to estimate associations of pressure and tilt with: (a) interval cancer (148 cases/625 age-matched controls) and (b) subsequent screen-detected cancer (344/1436), via condi-tional logistic regression. Results: Compression pressure was negatively associated with odds of BC at contemporaneous screen (odds ratio (OR) for top versus bottom third of the pressure distribution: 0.74; 95% CI 0.60, 0.92; P-for-linear-trend (Pt) = 0.007). There was weak evidence that moderate pressure at screening was associated with lower odds of interval cancer (OR for middle versus bottom third: 0.63; 95% CI 0.38, 1.05; p = 0.079), but no association was found between pressure and the odds of BC at subsequent screen. There was no evidence that paddle tilt was associated with the odds of contemporaneous, subsequent screen or interval cancer detection. Conclusions: Findings are consistent with compression pressure, but not paddle tilt, affecting the performance of mammographic screening by interfering with its ability to detect cancers. Advances in knowledge: Inadequate or excessive compression pressure at screening may contribute to a reduced ability to detect cancers, resulting in a greater number of interval cancer cases

Left-right breast asymmetry and risk of screen-detected and interval cancers in a large population-based screening population

OBJECTIVES: To assess the associations between automated volumetric estimates of mammographic asymmetry and breast cancers detected at the same ("contemporaneous") screen, at subsequent screens, or in between (interval cancers). METHODS: Automated measurements from mammographic images (N = 79,731) were used to estimate absolute asymmetry in breast volume (BV) and dense volume (DV) in a large ethnically diverse population of attendees of a UK breast screening programme. Logistic regression models were fitted to assess asymmetry associations with the odds of a breast cancer detected at contemporaneous screen (767 cases), adjusted for relevant confounders.Nested case-control investigations were designed to examine associations between asymmetry and the odds of: (a) interval cancer (numbers of cases/age-matched controls: 153/646) and (b) subsequent screen-detected cancer (345/1438), via conditional logistic regression. RESULTS: DV, but not BV, asymmetry was positively associated with the odds of contemporaneous breast cancer (P-for-linear-trend (Pt) = 0.018). This association was stronger for first (prevalent) screens (Pt = 0.012). Both DV and BV asymmetry were positively associated with the odds of an interval cancer diagnosis (Pt = 0.060 and 0.030, respectively). Neither BV nor DV asymmetry were associated with the odds of having a subsequent screen-detected cancer. CONCLUSIONS: Increased DV asymmetry was associated with the risk of a breast cancer diagnosis at a contemporaneous screen or as an interval cancer. BV asymmetry was positively associated with the risk of an interval cancer diagnosis. ADVANCES IN KNOWLEDGE: The findings suggest that DV and BV asymmetry may provide additional signals for detecting contemporaneous cancers and assessing the likelihood of interval cancers in population-based screening programmes

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition