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Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.
A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.
Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.
In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.
Selective laser sintering methods are workhorses for additively manufacturing polymer-based components. The ease of rapid prototyping also means it is easy to produce illicit components. It is necessary to have a data-calibrated in-situ physical model of the build process in order to predict expected and defective microstructure characteristics that inform component provenance. Toward this end, sintering models are calibrated and characteristics such as component defects are explored. This is accomplished by assimilating multiple data streams, imaging analysis, and computational model predictions in an adaptive Bayesian parameter estimation algorithm. From these data sources, along with a phase-field model, bulk porosity distributions are inferred. Model parameters are constrained to physically-relevant search directions by sensitivity analysis, and then matched to predictions using adaptive sampling. Using this feedback loop, data-constrained estimates of sintering model parameters along with uncertainty bounds are obtained.
Angiostrongylus cantonensis is a pathogenic nematode and the cause of neuroangiostrongyliasis, an eosinophilic meningitis more commonly known as rat lungworm disease. Transmission is thought to be primarily due to ingestion of infective third stage larvae (L3) in gastropods, on produce, or in contaminated water. The gold standard to determine the effects of physical and chemical treatments on the infectivity of A. cantonensis L3 larvae is to infect rodents with treated L3 larvae and monitor for infection, but animal studies are laborious and expensive and also raise ethical concerns. This study demonstrates propidium iodide (PI) to be a reliable marker of parasite death and loss of infective potential without adversely affecting the development and future reproduction of live A. cantonensis larvae. PI staining allows evaluation of the efficacy of test substances in vitro, an improvement upon the use of lack of motility as an indicator of death. Some potential applications of this assay include determining the effectiveness of various anthelmintics, vegetable washes, electromagnetic radiation and other treatments intended to kill larvae in the prevention and treatment of neuroangiostrongyliasis.
The purpose of this paper is to determine the origin of the photometric variations of 48 Lib using the data from the STEREO and to investigate their relations with the disk structure. The photometric data comprise a period of five years from 2007 to 2011. The spectroscopic data covering the same time interval are provided from the BeSS database. The Hα lines are examined by measuring their equivalent widths and line intensities. Hα variations are then compared with those displayed by the photometric data. From the photometry, high-precision results (10−5 c d−1 in frequency and 10−4 mag in amplitude) are obtained. It is detected that the star has shown 24 frequencies, mainly clustered around the peaks at 2.48896(1) and 5.08150(2) c d−1. The analysis reveals that the photometric frequencies are not due to pulsation, but caused by the rotation, and that the remaining frequencies arise from transient activities on or just above the photosphere. Also, it is shown that the spectroscopic data exhibit a significant Hα variability, and that the Hα line variation depends on the variation of frequency and amplitude, something which has been often proposed in the literature but has never before been demonstrated observationally. This proves that the disk structure and photometric variations are related.
The aim of this study is to accurately calculate the rotational period of CS Vir by using STEREO observations and investigate a possible period variation of the star with the help of all accessible data. The STEREO data that cover 5-yr time interval between 2007 and 2011 are analysed by means of the Lomb–Scargle and Phase Dispersion Minimization methods. In order to obtain a reliable rotation period and its error value, computational algorithms such as the Levenberg–Marquardt and Monte Carlo simulation algorithms are applied to the data sets. Thus, the rotation period of CS Vir is improved to be 9.29572(12) d by using the 5-yr of combined data set. Also, the light elements are calculated as HJDmax = 2454715.975(11) + 9d· 29572(12) × E + 9d· 78(1.13) × 10 − 8 × E2 by means of the extremum times derived from the STEREO light curves and archives. Moreover, with this study, a period variation is revealed for the first time, and it is found that the period has lengthened by 0.66(8) s y−1, equivalent to 66 s per century. Additionally, a time-scale for a possible spin-down is calculated around τSD ~ 106 yr. The differential rotation and magnetic braking are thought to be responsible of the mentioned rotational deceleration. It is deduced that the spin-down time-scale of the star is nearly three orders of magnitude shorter than its main-sequence lifetime (τMS ~ 109 yr). It is, in return, suggested that the process of increase in the period might be reversible.
An internationally approved and globally used classification scheme for the diagnosis of CHD has long been sought. The International Paediatric and Congenital Cardiac Code (IPCCC), which was produced and has been maintained by the International Society for Nomenclature of Paediatric and Congenital Heart Disease (the International Nomenclature Society), is used widely, but has spawned many “short list” versions that differ in content depending on the user. Thus, efforts to have a uniform identification of patients with CHD using a single up-to-date and coordinated nomenclature system continue to be thwarted, even if a common nomenclature has been used as a basis for composing various “short lists”. In an attempt to solve this problem, the International Nomenclature Society has linked its efforts with those of the World Health Organization to obtain a globally accepted nomenclature tree for CHD within the 11th iteration of the International Classification of Diseases (ICD-11). The International Nomenclature Society has submitted a hierarchical nomenclature tree for CHD to the World Health Organization that is expected to serve increasingly as the “short list” for all communities interested in coding for congenital cardiology. This article reviews the history of the International Classification of Diseases and of the IPCCC, and outlines the process used in developing the ICD-11 congenital cardiac disease diagnostic list and the definitions for each term on the list. An overview of the content of the congenital heart anomaly section of the Foundation Component of ICD-11, published herein in its entirety, is also included. Future plans for the International Nomenclature Society include linking again with the World Health Organization to tackle procedural nomenclature as it relates to cardiac malformations. By doing so, the Society will continue its role in standardising nomenclature for CHD across the globe, thereby promoting research and better outcomes for fetuses, children, and adults with congenital heart anomalies.
Hippocampal volume reductions in major depression have been frequently reported. However, evidence for functional abnormalities in the same region in depression has been less clear. We investigated hippocampal function in depression using functional magnetic resonance imaging (fMRI) and neuropsychological tasks tapping spatial memory function, with complementing measures of hippocampal volume and resting blood flow to aid interpretation.
A total of 20 patients with major depressive disorder (MDD) and a matched group of 20 healthy individuals participated. Participants underwent multimodal magnetic resonance imaging (MRI): fMRI during a spatial memory task, and structural MRI and resting blood flow measurements of the hippocampal region using arterial spin labelling. An offline battery of neuropsychological tests, including several measures of spatial memory, was also completed.
The fMRI analysis showed significant group differences in bilateral anterior regions of the hippocampus. While control participants showed task-dependent differences in blood oxygen level-dependent (BOLD) signal, depressed patients did not. No group differences were detected with regard to hippocampal volume or resting blood flow. Patients showed reduced performance in several offline neuropsychological measures. All group differences were independent of differences in hippocampal volume and hippocampal blood flow.
Functional abnormalities of the hippocampus can be observed in patients with MDD even when the volume and resting perfusion in the same region appear normal. This suggests that changes in hippocampal function can be observed independently of structural abnormalities of the hippocampus in depression.
Individuals with the short variant of the serotonin transporter linked polymorphic region gene are more susceptible than individuals homozygous for the long allele to the effects of stressful life events on risk for internalizing and externalizing problems. We tested whether individual differences in coping style explained this increased risk for problem behavior among youth who were at both genetic and environmental risk. Participants included 279 children, ages 8–11, from the Children's Experiences and Development Study. Caregivers and teachers reported on children's internalizing and externalizing symptoms, and caregivers and children on children's exposure to harsh parenting and parental warmth in middle childhood, and traumatic events. Children reported how frequently they used various coping strategies. Results revealed that short/short homozygotes had higher levels of internalizing problems compared with long allele carriers and that short allele carriers had higher levels of externalizing problems compared with long/long homozygotes under conditions of high cumulative risk. Moreover, among children who were homozygous for the short allele, those who had more cumulative risk indicators less frequently used distraction coping strategies, which partly explained why they had higher levels of internalizing problems. Coping strategies did not significantly mediate Gene × Environment effects on externalizing symptoms.
Insecticidal activities of five pesticidal plant species, Tephrosia vogelii, Dysphania (Syn: Chenopodium) ambrosioides, Lippia javanica, Tithonia diversifolia and Vernonia amygdalina, which have been reported to control storage pests, were evaluated as leaf powders against Callosobruchus maculatus (Fabricius 1775) in stored cowpea. Their efficacy was compared with the commercial pesticide Actellic dust (pirimiphos-methyl) at the recommended concentration (50 g/90 kg), and with untreated cowpea seeds as a negative control. The plant powders were applied at concentrations of 0.01, 0.1, 1 and 3 g/10 g of cowpea seeds in 250 ml plastic containers (to measure contact toxicity), or 0.005, 0.05, 0.5 and 5 g tied in small muslin cloth bags and hung in 500 ml plastic bottles containing 10 g of cowpea seeds (to measure fumigant toxicity). Mortality of adults, oviposition deterrence, adult emergence, and percent seed damage were recorded. Complete protection of seeds and inhibition of adult emergence were achieved in Actellic dust-treated seeds; contact toxicity using leaf powders of T. vogelii at all concentrations, D. ambrosioides at concentrations of 0.1, 1 and 3 g and L. javanica at concentrations of 1 and 3 g; and fumigant toxicity using D. ambrosioides at concentrations of 0.5 and 5 g and L. javanica at a concentration of 5 g. Head space analysis of D. ambrosioides and L. javanica identified ascaridole and camphor, respectively, as components that could be responsible for the bioactivity of these plant species. These plants may, therefore, serve as effective but less harmful biopesticide alternatives to Actellic. Conversely, V. amygdalina and T. diversifolia were not effective, indicating that they should not be promoted for controlling bruchids in cowpea.