Neonatal patients are particularly appropriate for utilization of diagnostic exome sequencing (DES), as many Mendelian diseases are known to present in this period of life but often with complex, ...heterogeneous features. We attempted to determine the diagnostic rates and features of neonatal patients undergoing DES.
The clinical histories and results of 66 neonatal patients undergoing DES were retrospectively reviewed.
Clinical DES identified potentially relevant findings in 25 patients (37.9%). The majority of patients had structural anomalies such as birth defects, dysmorphic features, cardiac, craniofacial, and skeletal defects. The average time for clinical rapid testing was 8 days.
Our observations demonstrate the utility of family-based exome sequencing in neonatal patients, including familial cosegregation analysis and comprehensive medical review.
Polyphosphazenes are a class of inorganic polymers characterized by the phosphorus nitrogen repeating unit that forms the backbone. The phosphorus is pentavalent and the backbone has alternating ...single and double bonds. This leaves two coordination sites on the phosphorus free for substituted with a variety of nucleophilic groups. Several hundred polyphosphazene formulations have been reported in the literature. The ease of controlling the type and number of substituents provides a unique opportunity to develop special series of polymers to investigate structure property relationships. In this paper the pure gas permeabilities of a series of substituted bisphenoxyphosphazene polymers is reported. The polymers were exposed to ten different gases and the resulting permeabilities were analyzed using the time lag method. The time lag method enables the permeability to be broken down into its solubility and diffusivity components. Careful examination of the results makes it possible to determine what types of substituent-gas interactions are responsible for the overall permeabilities in the polymers. Some of the polymers showed low permeabilities for all of the test gases, while others showed very large differences among the different gases tested. Especially interesting differences were observed for the series of alkanes tested. The results permit the prediction of what types of mixed gas separations might be worth pursuing.
Research has been conducted at the Idaho National Engineering and Environmental Laboratory to determine the characteristics of phosphazene polymers when used as membranes for chemical separations. ...Phosphazene chemistry allows tailoring of the polymers' mechanical and chemical properties to suit particular applications. Separations discussed in this paper are models for several applications needed in the chemical industry. Ligands on the polymers tested have included modified sugars, various glycols, and substituted phenols. In some cases all of the substituents on the polymer were the same entity. In other cases, up to three different ligands were attached in attempt to develop polymers with all of the needed properties. Physical properties of the different materials varied from film forming rubbers to sticky materials. Some of the polymers gave good fluxes, excellent separations, and lasted for weeks, while others started out with good properties but failed rapidly. A description of the separation performance relative to the separation of isopropanol from dye is given in this paper.
Pediatric low-grade gliomas (pLGG) are frequently driven by genetic alterations in the RAS-mitogen-activated protein kinase (RAS/MAPK) pathway yet show unexplained variability in their clinical ...outcome. To address this, we characterized a cohort of >1,000 clinically annotated pLGG. Eighty-four percent of cases harbored a driver alteration, while those without an identified alteration also often exhibited upregulation of the RAS/MAPK pathway. pLGG could be broadly classified based on their alteration type. Rearrangement-driven tumors were diagnosed at a younger age, enriched for WHO grade I histology, infrequently progressed, and rarely resulted in death as compared with SNV-driven tumors. Further sub-classification of clinical-molecular correlates stratified pLGG into risk categories. These data highlight the biological and clinical differences between pLGG subtypes and opens avenues for future treatment refinement.
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•KIAA1549-BRAF, BRAF p.V600E, and NF1 mutations account for 2/3 of pLGG•Activation of the RAS/MAPK pathway is nearly universal in pLGG•pLGG comprise two distinct clinical subgroups: rearrangement- or SNV-driven•Risk stratification based on alteration type effectively predicts patient outcome
Ryall et al. perform a comprehensive analysis of the molecular underpinnings and clinical correlates of 1000 pediatric low-grade gliomas. They uncover unique clinical features based on the type of molecular alteration identified and provide a risk based stratification to help infer treatment decisions.
Clinical studies have been inconclusive about the effectiveness of N95 respirators and medical masks in preventing health care personnel (HCP) from acquiring workplace viral respiratory infections.
...To compare the effect of N95 respirators vs medical masks for prevention of influenza and other viral respiratory infections among HCP.
A cluster randomized pragmatic effectiveness study conducted at 137 outpatient study sites at 7 US medical centers between September 2011 and May 2015, with final follow-up in June 2016. Each year for 4 years, during the 12-week period of peak viral respiratory illness, pairs of outpatient sites (clusters) within each center were matched and randomly assigned to the N95 respirator or medical mask groups.
Overall, 1993 participants in 189 clusters were randomly assigned to wear N95 respirators (2512 HCP-seasons of observation) and 2058 in 191 clusters were randomly assigned to wear medical masks (2668 HCP-seasons) when near patients with respiratory illness.
The primary outcome was the incidence of laboratory-confirmed influenza. Secondary outcomes included incidence of acute respiratory illness, laboratory-detected respiratory infections, laboratory-confirmed respiratory illness, and influenzalike illness. Adherence to interventions was assessed.
Among 2862 randomized participants (mean SD age, 43 11.5 years; 2369 82.8%) women), 2371 completed the study and accounted for 5180 HCP-seasons. There were 207 laboratory-confirmed influenza infection events (8.2% of HCP-seasons) in the N95 respirator group and 193 (7.2% of HCP-seasons) in the medical mask group (difference, 1.0%, 95% CI, -0.5% to 2.5%; P = .18) (adjusted odds ratio OR, 1.18 95% CI, 0.95-1.45). There were 1556 acute respiratory illness events in the respirator group vs 1711 in the mask group (difference, -21.9 per 1000 HCP-seasons 95% CI, -48.2 to 4.4; P = .10); 679 laboratory-detected respiratory infections in the respirator group vs 745 in the mask group (difference, -8.9 per 1000 HCP-seasons, 95% CI, -33.3 to 15.4; P = .47); 371 laboratory-confirmed respiratory illness events in the respirator group vs 417 in the mask group (difference, -8.6 per 1000 HCP-seasons 95% CI, -28.2 to 10.9; P = .39); and 128 influenzalike illness events in the respirator group vs 166 in the mask group (difference, -11.3 per 1000 HCP-seasons 95% CI, -23.8 to 1.3; P = .08). In the respirator group, 89.4% of participants reported "always" or "sometimes" wearing their assigned devices vs 90.2% in the mask group.
Among outpatient health care personnel, N95 respirators vs medical masks as worn by participants in this trial resulted in no significant difference in the incidence of laboratory-confirmed influenza.
ClinicalTrials.gov Identifier: NCT01249625.
Mental illness among adolescents frequently goes untreated, especially among low income and ethnic minority families. We sought to examine parent and adolescent psychological factors influencing ...mental health service use among 120 urban adolescents (82% African American, Age 13-18 years, M = 14.29, SD = 1.52) who had access to mental health treatment through their community primary care setting. We utilized structural equation modeling (SEM) to explore the independent and combined associations among parent and adolescent variables hypothesized to be associated with the youth's engagement in mental health treatment. Results showed that more than half (63.6%) of youth with clinically significant levels of symptoms were not currently engaged in treatment or seeking mental health services. One latent variable emerged: caregivers' perceptions of adolescent mental health problems (consisted of youth psychological symptoms, youth functional impairment, and strain on caregiver). Together with caregivers' attitude toward professional help, these two caregiver-reported variables, but not adolescents' attitude, were associated with higher likelihood of service utilization among adolescents. Findings suggest caregivers functioned as the "gatekeepers" to mental health services. We discuss findings' implications for engaging youth in mental health services as well as study limitations and future directions.
Public Policy Relevance Statement
Most adolescents with mental health problems do not engage in available treatments. This study found that parents served as gatekeepers and sought help when they hold positive attitudes toward professional help and viewed their teens' behavior problems as (a) numerous, (b) impairing youth functioning, and (c) increasing parental stress. More ways are needed to facilitate parental engagement in active adolescent mental health treatment decision as well as encouraging adolescent input during the decision-making process.
Youth, particularly urban minority youth, are exposed to high levels of stressful and potentially traumatic life events that have been linked to a wide array of negative outcomes including ...internalizing and externalizing problems. Youth perceptions of their interpersonal relationship quality with caregivers and friends were examined as potential promotive and protective factors counteracting the link between exposure to stressful and traumatic events and behavior problems. Participants were 85 urban, predominantly African American of age 13–17 years (60% girls). Results supported the hypothesis that youth report of parent trust and communication would serve as a promotive and protective factor, moderating the association between stressful life events and behavior problems. In contrast, peer trust and communication did not appear to counteract the association between stress and behavior problems. Instead, reports of trust and communication with friends appeared to increase the association between stress exposure and internalizing problems.
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