Loneliness in the lives of Danish adolescents: Associations with health and sleep

Aim. We examined the relationship between loneliness and health among young adolescents. We also investigated the validity of a single item measure of loneliness by comparing this to a composite score. Methods. The current data comes from a nationally representative sample of 11-15 year old adolescents (N = 3305; F = 52%) from Denmark collected in 2014 as part of the Health Behaviour in School-aged Children (HBSC) collaborative cross-national survey. Results. A series of binary logistic regressions showed that higher loneliness among adolescents, whether measured using the single- or multi-item measurement, was associated with poorer self-rated health, higher frequency of headache, stomach-ache, back-ache, difficulties sleeping, greater sleep disturbance, and more instances of feeling tired in the morning. Those associations were relatively consistent across gender and age groups. Conclusions. Loneliness is associated with poorer self-reported health and sleep problems among young adolescents. Those findings are similar across two measures of loneliness, suggesting robust findings. The development of interventions and health education efforts to fight loneliness in adolescence is important

Efficacy of Online Training for Improving Camp Staff Competency

Preparing competent staff is a critical issue within the camp community. This quasi-experimental study examined the effectiveness of an online course for improving staff competency in camp healthcare practices among college-aged camp staff and a comparison group (N = 55). We hypothesized that working in camp would increase competency test scores due to opportunities for staff to experientially apply knowledge learned online. Hierarchical linear modeling was used to analyse the cross-level effects of a between-individuals factor (assignment to experimental or comparison group) and within-individual effects of time (pre-test, post-test #1, and post-test #2) on online course test scores. At post-test #2, the difference in average test scores between groups was ~30 points, with the treatment group scoring lower on average than the comparison group. Factors that may have influenced these findings are explored, including fatigue and the limited durability of online learning. Recommendations for research and practice are discussed

A comparative study of microwave and barrier discharge plasma for the regeneration of spent zeolite catalysts

Due to their acid characteristics and pore structure, which can induce high product selectivity; zeolite catalysts are used extensively in industry to catalyse reactions involving hydrocarbons. However, these catalysts can suffer from deactivation due to cracking reactions that result in the deposition of carbon leading to poisoning of the acid sites and blocking of the pores [1]. Depending upon the reaction and the particular catalyst involved this deactivation may take place over several months or even years but in some cases occurs in minutes. Therefore, zeolite catalysts are frequently reactivated / regenerated. This generally involves a thermal treatment involving air which results in oxidation of the carbon [2]. However, the oxidation of carbon is highly exothermic, and if not carefully controlled, results in the generation of exceedingly high localized temperatures which can destroy the zeolite structure and result in subsequent loss of catalyst activity. More conservative thermal treatments can result in incomplete regeneration and again a catalyst displaying inferior activity. This paper explores the use of non-thermal plasma which had been either generated using microwaves or via a barrier discharge to regenerate spent zeolite catalysts. The catalyst, H-mordenite, was tested for the disproportionation of toluene (Figure 1) using conventional heating. The spent catalyst was then regenerated using a plasma or conventional thermal treatment before having its activity re-evaluated for the toluene disproportionation reaction as previous. Fig. 1. Reaction Scheme for Toluene Disproportionation. Interestingly, not only is plasma regeneration highly effective but also catalysts can be regenerated in greatly reduced times. There is an additional advantage in that plasma regeneration can impart physical properties that result in a zeolite that is resistant to further deactivation. However, the results are highly dependent upon the experimental conditions involved for plasma regeneration. References Wu J, Leu L., Appl. Catal., 1983; 7:283-294. M. Guisnet and P. Magnoux, Deactivation of Zeolites by Coking. Prevention of Deactivation and Regeneration. In: Zeolite Microporous Solids: Synthesis, Structure, and Reactivity. E.G. Derouane, F Lemos, C. Naccache, F. Ramôa Ribeiro, Eds. Pages 437-456. Springer 1992

Academic self-concept, gender and single-sex schooling

This paper assesses gender differences in academic self-concept for a cohort of children born in 1958 (the National Child Development Study). We address the question of whether attending single-sex or co-educational schools affected students’ perceptions of their own academic abilities (academic self-concept). Academic selfconcept was found to be highly gendered, even controlling for prior test scores. Boys had higher self-concepts in maths and science, and girls in English. Single-sex schooling reduced the gender gap in self-concept, while selective schooling was linked to lower academic self-concept overall

Quantifying prediction of pathogenicity for within-codon concordance (PM5) using 7541 functional classifications of BRCA1 and MSH2 missense variants.

PURPOSE: Conditions and thresholds applied for evidence weighting of within-codon concordance (PM5) for pathogenicity vary widely between laboratories and expert groups. Because of the sparseness of available clinical classifications, there is little evidence for variation in practice. METHODS: We used as a truthset 7541 dichotomous functional classifications of BRCA1 and MSH2, spanning 311 codons of BRCA1 and 918 codons of MSH2, generated from large-scale functional assays that have been shown to correlate excellently with clinical classifications. We assessed PM5 at 5 stringencies with incorporation of 8 in silico tools. For each analysis, we quantified a positive likelihood ratio (pLR, true positive rate/false positive rate), the predictive value of PM5-lookup in ClinVar compared with the functional truthset. RESULTS: pLR was 16.3 (10.6-24.9) for variants for which there was exactly 1 additional colocated deleterious variant on ClinVar, and the variant under examination was equally or more damaging when analyzed using BLOSUM62. pLR was 71.5 (37.8-135.3) for variants for which there were 2 or more colocated deleterious ClinVar variants, and the variant under examination was equally or more damaging than at least 1 colocated variant when analyzed using BLOSUM62. CONCLUSION: These analyses support the graded use of PM5, with potential to use it at higher evidence weighting where more stringent criteria are met

Cancer Variant Interpretation Group UK (CanVIG-UK): an exemplar national subspecialty multidisciplinary network.

Advances in technology have led to a massive expansion in the capacity for genomic analysis, with a commensurate fall in costs. The clinical indications for genomic testing have evolved markedly; the volume of clinical sequencing has increased dramatically; and the range of clinical professionals involved in the process has broadened. There is general acceptance that our early dichotomous paradigms of variants being pathogenic-high risk and benign-no risk are overly simplistic. There is increasing recognition that the clinical interpretation of genomic data requires significant expertise in disease-gene-variant associations specific to each disease area. Inaccurate interpretation can lead to clinical mismanagement, inconsistent information within families and misdirection of resources. It is for this reason that 'national subspecialist multidisciplinary meetings' (MDMs) for genomic interpretation have been articulated as key for the new NHS Genomic Medicine Service, of which Cancer Variant Interpretation Group UK (CanVIG-UK) is an early exemplar. CanVIG-UK was established in 2017 and now has >100 UK members, including at least one clinical diagnostic scientist and one clinical cancer geneticist from each of the 25 regional molecular genetics laboratories of the UK and Ireland. Through CanVIG-UK, we have established national consensus around variant interpretation for cancer susceptibility genes via monthly national teleconferenced MDMs and collaborative data sharing using a secure online portal. We describe here the activities of CanVIG-UK, including exemplar outputs and feedback from the membership

Not Perfect, but Better: Primary Care Providers’ Experiences with Electronic Referrals in a Safety Net Health System

BackgroundElectronic referrals can improve access to subspecialty care in safety net settings. In January 2007, San Francisco General Hospital (SFGH) launched an electronic referral portal that incorporated subspecialist triage, iterative communication with referring providers, and existing electronic health record data to improve access to subspecialty care.ObjectiveWe surveyed primary care providers (PCPs) to assess the impact of electronic referrals on workflow and clinical care.DesignWe administered an 18-item, web-based questionnaire to all 368 PCPs who had the option of referring to SFGH.MeasurementsWe asked participants to rate time spent submitting a referral, guidance of workup, wait times, and change in overall clinical care compared to prior referral methods using 5-point Likert scales. We used multivariate logistic regression to identify variables associated with perceived improvement in overall clinical care.ResultsTwo hundred ninety-eight PCPs (81.0%) from 24 clinics participated. Over half (55.4%) worked at hospital-based clinics, 27.9% at county-funded community clinics, and 17.1% at non-county-funded community clinics. Most (71.9%) reported that electronic referrals had improved overall clinical care. Providers from non-county-funded clinics (AOR 0.40, 95% CI 0.14-0.79) and those who spent > or =6 min submitting an electronic referral (AOR 0.33, 95%CI 0.18-0.61) were significantly less likely than other participants to report that electronic referrals had improved clinical care.ConclusionsPCPs felt electronic referrals improved health-care access and quality; those who reported a negative impact on workflow were less likely to agree. While electronic referrals hold promise as a tool to improve clinical care, their impact on workflow should be considered

Joint hypermobility links neurodivergence to dysautonomia and pain

Objectives: Autism, attention deficit hyperactivity disorder (ADHD), and tic disorder (Tourette syndrome; TS) are neurodevelopmental conditions that frequently co-occur and impact psychological, social, and emotional processes. Increased likelihood of chronic physical symptoms, including fatigue and pain, are also recognized. The expression of joint hypermobility, reflecting a constitutional variant in connective tissue, predicts susceptibility to psychological symptoms alongside recognized physical symptoms. Here, we tested for increased prevalence of joint hypermobility, autonomic dysfunction, and musculoskeletal symptoms in 109 adults with neurodevelopmental condition diagnoses. Methods: Rates of generalized joint hypermobility (GJH, henceforth hypermobility) in adults with a formal diagnosis of neurodevelopmental conditions (henceforth neurodivergent group, n = 109) were compared to those in the general population in UK. Levels of orthostatic intolerance and musculoskeletal symptoms were compared to a separate comparison group (n = 57). Age specific cut-offs for GJH were possible to determine in the neurodivergent and comparison group only. Results: The neurodivergent group manifested elevated prevalence of hypermobility (51%) compared to the general population rate of 20% and a comparison population (17.5%). Using a more stringent age specific cut-off, in the neurodivergent group this prevalence was 28.4%, more than double than the comparison group (12.5%). Odds ratio for presence of hypermobility in neurodivergent group, compared to the general population was 4.51 (95% CI 2.17–9.37), with greater odds in females than males. Using age specific cut-off, the odds ratio for GJH in neurodivergent group, compared to the comparison group, was 2.84 (95% CI 1.16–6.94). Neurodivergent participants reported significantly more symptoms of orthostatic intolerance and musculoskeletal skeletal pain than the comparison group. The number of hypermobile joints was found to mediate the relationship between neurodivergence and symptoms of both dysautonomia and pain. Conclusions: In neurodivergent adults, there is a strong link between the expression of joint hypermobility, dysautonomia, and pain, more so than in the comparison group. Moreover, joint hypermobility mediates the link between neurodivergence and symptoms of dysautonomia and pain. Increased awareness and understanding of this association may enhance the management of core symptoms and allied difficulties in neurodivergent people, including co-occurring physical symptoms, and guide service delivery in the future

Quantifying evidence toward pathogenicity for rare phenotypes: The case of succinate dehydrogenase genes, SDHB and SDHD.

PURPOSE: The weight of the evidence to attach to observation of a novel rare missense variant in SDHB or SDHD in individuals with the rare neuroendocrine tumors, pheochromocytomas and paragangliomas (PCC/PGL), is uncertain. METHODS: We compared the frequency of SDHB and SDHD very rare missense variants (VRMVs) in 6328 and 5847 cases of PCC/PGL, respectively, with that of population controls to generate a pan-gene VRMV likelihood ratio (LR). Via windowing analysis, we measured regional enrichments of VRMVs to calculate the domain-specific VRMV-LR (DS-VRMV-LR). We also calculated subphenotypic LRs for variant pathogenicity for various clinical, histologic, and molecular features. RESULTS: We estimated the pan-gene VRMV-LR to be 76.2 (54.8-105.9) for SDHB and 14.8 (8.7-25.0) for SDHD. Clustering analysis revealed an SDHB enriched region (ɑɑ 177-260, P = .001) for which the DS-VRMV-LR was 127.2 (64.9-249.4) and an SDHD enriched region (ɑɑ 70-114, P = .000003) for which the DS-VRMV-LR was 33.9 (14.8-77.8). Subphenotypic LRs exceeded 6 for invasive disease (SDHB), head-and-neck disease (SDHD), multiple tumors (SDHD), family history of PCC/PGL, loss of SDHB staining on immunohistochemistry, and succinate-to-fumarate ratio >97 (SDHB, SDHD). CONCLUSION: Using methodology generalizable to other gene-phenotype dyads, the LRs relating to rarity and phenotypic specificity for a single observation in PCC/PGL of a SDHB/SDHD VRMV can afford substantial evidence toward pathogenicity

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations