Ten‐Year Secular Trends in Youth Violence: Results From the Philadelphia Youth Risk Behavior Survey 2003‐2013

BACKGROUNDYouth violence reduction is a public health priority, yet few studies have examined secular trends in violence among urban youth, who may be particularly vulnerable to numerous forms of violence. This study examines 10‐year secular trends in the prevalence of violence‐related behaviors among Philadelphia high school students.METHODSRepeated cross‐sectional data were analyzed from 5 waves of the Philadelphia Youth Risk Behavior Survey (YRBS) from 2003 to 2013. Sex‐specific multivariate regression models were used to examine secular trends in multiple types of violence, accounting for age, race/ethnicity, and sampling strategy.RESULTSIn 2013, the most prevalent violent behavior was physical fighting among boys (38.4%) and girls (32.7%). Among girls, the prevalence of sexual assault and suicide attempts declined between 2003 and 2013 (β = −0.13, p = .04 and β = −0.14, p = .007, respectively). Among boys, significant declines in carrying a weapon (β = −0.31, p < .001), carrying a gun (β = −0.16, p = .01), and physical fighting (β = −0.35, p = .001) were observed.CONCLUSIONSWhereas the prevalence of some forms of violence stabilized or declined among Philadelphia youth during 2003‐2013 time span, involvement in violence‐related behaviors remains common among this population. Continued surveillance and evidence‐based violence reduction strategies are needed to address violence among urban youth.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136403/1/josh12491_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136403/2/josh12491.pd

ADAMTS19-associated heart valve defects: Novel genetic variants consolidating a recognizable cardiac phenotype

Recently, ADAMTS19 was identified as a novel causative gene for autosomal recessive heart valve disease (HVD), affecting mainly the aortic and pulmonary valves. Exome sequencing and data repository (CentoMD) analyses were performed to identify patients with ADAMTS19 variants (two families). A third family was recognized based on cardiac phenotypic similarities and SNP array homozygosity. Three novel loss of function (LoF) variants were identified in six patients from three families. Clinically, all patients presented anomalies of the aortic/pulmonary valves, which included thickening of valve leaflets, stenosis and insufficiency. Three patients had (recurrent) subaortic membrane, suggesting that ADAMTS19 is the first gene identified related to discrete subaortic stenosis. One case presented a bi-commissural pulmonary valve. All patients displayed some degree of atrioventricular valve insufficiency. Other cardiac anomalies included atrial/ventricular septal defects, persistent ductus arteriosus, and mild dilated ascending aorta. Our findings confirm that biallelic LoF variants in ADAMTS19 are causative of a specific and recognizable cardiac phenotype. We recommend considering ADAMTS19 genetic testing in all patients with multiple semilunar valve abnormalities, particularly in the presence of subaortic membrane. ADAMTS19 screening in patients with semilunar valve abnormalities is needed to estimate the frequency of the HVD related phenotype, which might be not so rare

Family physicians' effort to stay in charge of the medical treatment when patients have home care by district nurses. A grounded theory study

<p>Abstract</p> <p>Background</p> <p>District nurses (DNs) provide home care for old persons with a mixture of chronic diseases, symptoms and reduced functional ability. Family physicians (FPs) have been criticised for their lack of involvement in this care. The aim of this study was to obtain increased knowledge concerning the FP's experience of providing medical treatment for patients with home care provided by DNs by developing a theoretical model that elucidates how FPs handle the problems they encounter regarding the individual patients and their conditions.</p> <p>Methods</p> <p>Semi-structured interviews were conducted with 13 Swedish FPs concerning one of their registered patients with home care by a DN, and the treatment of this patient. Grounded theory methodology (GTM) was used in the analyses.</p> <p>Results</p> <p>The core category was the effort to stay in charge of the medical treatment. This involved three types of problems: gaining sufficient insight, making adequate decisions, and maintaining appropriate medical treatment. For three categories of patients, the FPs had problems staying in charge. Patients with reduced functional ability had problems providing information and maintaining treatment. Patients who were "fixed in their ways" did not provide information and did not comply with recommendations, and for patients with complex conditions, making adequate decisions could be problematic. To overcome the problems, four different strategies were used: relying on information from others, supporting close observation and follow-up by others, being constantly ready to change the goal of the treatment, and relying on others to provide treatment.</p> <p>Conclusion</p> <p>The patients in this study differed from most other patients seen at the healthcare centre as the consultation with the patient could not provide the usual foundation for decisions concerning medical treatment. Information from and collaboration with the DN and other home care providers was essential for the FP's effort to stay in charge of the medical treatment. The complexity of the situation made it problematic for the FP to make adequate decisions about the goal of the medical treatment. The goal of the treatment had to be constantly evaluated based on information from the DN and other care providers, and thus this information was absolutely crucial.</p

The Assembly of the Plasmodial PLP Synthase Complex Follows a Defined Course

Background: Plants, fungi, bacteria and the apicomplexan parasite Plasmodium falciparum are able to synthesize vitamin B6 de novo, whereas mammals depend upon the uptake of this essential nutrient from their diet. The active form of vitamin B6 is pyridoxal 5-phosphate (PLP). For its synthesis two enzymes, Pdx1 and Pdx2, act together, forming a multimeric complex consisting of 12 Pdx1 and 12 Pdx2 protomers. Methodology/Principal Findings: Here we report amino acid residues responsible for stabilization of the structural and enzymatic integrity of the plasmodial PLP synthase, identified by using distinct mutational analysis and biochemical approaches. Residues R85, H88 and E91 (RHE) are located at the Pdx1:Pdx1 interface and play an important role in Pdx1 complex assembly. Mutation of these residues to alanine impedes both Pdx1 activity and Pdx2 binding. Furthermore, changing D26, K83 and K151 (DKK), amino acids from the active site of Pdx1, to alanine obstructs not only enzyme activity but also formation of the complex. In contrast to the monomeric appearance of the RHE mutant, alteration of the DKK residues results in a hexameric assembly, and does not affect Pdx2 binding or its activity. While the modelled position of K151 is distal to the Pdx1:Pdx1 interface, it affects the assembly of hexameric Pdx1 into a functional dodecamer, which is crucial for PLP synthesis. Conclusions/Significance: Taken together, our data suggest that the assembly of a functional Pdx1:Pdx2 complex follows

Bmp and Nodal Independently Regulate lefty1 Expression to Maintain Unilateral Nodal Activity during Left-Right Axis Specification in Zebrafish

In vertebrates, left-right (LR) axis specification is determined by a ciliated structure in the posterior region of the embryo. Fluid flow in this ciliated structure is responsible for the induction of unilateral left-sided Nodal activity in the lateral plate mesoderm, which in turn regulates organ laterality. Bmp signalling activity has been implied in repressing Nodal expression on the right side, however its mechanism of action has been controversial. In a forward genetic screen for mutations that affect LR patterning, we identified the zebrafish linkspoot (lin) mutant, characterized by cardiac laterality and mild dorsoventral patterning defects. Mapping of the lin mutation revealed an inactivating missense mutation in the Bmp receptor 1aa (bmpr1aa) gene. Embryos with a mutation in lin/bmpr1aa and a novel mutation in its paralogue, bmpr1ab, displayed a variety of dorsoventral and LR patterning defects with increasing severity corresponding with a decrease in bmpr1a dosage. In Bmpr1a-deficient embryos we observed bilateral expression of the Nodal-related gene, spaw, coupled with reduced expression of the Nodal-antagonist lefty1 in the midline. Using genetic models to induce or repress Bmp activity in combination with Nodal inhibition or activation, we found that Bmp and Nodal regulate lefty1 expression in the midline independently of each other. Furthermore, we observed that the regulation of lefty1 by Bmp signalling is required for its observed downregulation of Nodal activity in the LPM providing a novel explanation for this phenomenon. From these results we propose a two-step model in which Bmp regulates LR patterning. Prior to the onset of nodal flow and Nodal activation, Bmp is required to induce lefty1 expression in the midline. When nodal flow has been established and Nodal activity is apparent, both Nodal and Bmp independently are required for lefty1 expression to assure unilateral Nodal activation and correct LR patterning

Gorenstein Formats, Canonical and Calabi–Yau Threefolds

Gorenstein formats present the equations of regular canonical, Calabi–Yau and Fano varieties embedded by subcanonical divisors. We present a new algorithm for the enumeration of these formats based on orbifold Riemann-Roch and knapsack packing-type algorithms. We apply this to extend the known lists of threefolds of general type beyond the well-known classes of complete intersections and also to find classes of Calabi-Yau threefolds with canonical singularities

What we learn about bipolar disorder from large-scale neuroimaging:Findings and future directions from the ENIGMA Bipolar Disorder Working Group

MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness