Angiomatoid Fibrous Histiocytoma With ALK Expression in an Unusual Location and Age Group

Angiomatoid fibrous histiocytoma (AFH) is a relatively rare soft tissue tumor of intermediate malignant potential, occurring most commonly in young adults, with a recognized propensity for local recurrence and occasional metastasis. A case of AFH occurring on the finger of a 60-year-old man is described in which the unusual location and age group for this entity raised the original wrong diagnosis of an aneurysmal and cellular fibrous histiocytoma. Further workup demonstrated an EWSR1-CREB1 translocation, confirming the correct diagnosis of AFH. Strong anaplastic lymphoma kinase (ALK) expression using the antibody clone D5F3 was demonstrated in our case on immunohistochemistry, which is in concordance with recent findings of anaplastic lymphoma kinase positivity with this antibody in the majority of AFHs

Contemporary practices of strength and conditioning coaches in professional soccer

This study describes the contemporary practices of strength and conditioning coaches in professional soccer. Fifty-two strength and conditioning coaches from professional leagues across 18 countries completed an online survey, consisting of 45 questions, with eight sections: (a) background information, (b) muscular strength and power development, (c) speed development, (d) plyometrics, (e) flexibility development, (f) physical testing, (g) technology use, and (h) programing. A frequency analysis was used to assess and report responses to fixed response questions, and thematic-analysis used for open-ended questions to create clear, identifiable and distinct themes. All strength and conditioning coaches were educated to degree level or higher, 65% held strength and conditioning certifications and 54% held soccer coaching certifications. Concentric (100%) and eccentric (98%) modes of resistance were the most commonly prescribed, whereas the squat (including variations) (52%) was deemed the most important exercise for soccer players. Hang clean (33%) and multiple hops/lunges (89%) were the most programed Olympic weightlifting and plyometric exercises. Global Positioning Systems (94%) were the most utilized technology-based equipment. Time, scheduling and fixtures were the biggest issues faced, which made it difficult to periodize training programs and apply appropriate training loads. Furthermore, strength and conditioning coaches would like to further integrate technology to comprehensively monitor and test players, while also believing that technology will continue to be developed and integrated in the future. Strength and conditioning coaches from professional soccer can use the information from this study to review current practices and also provide ideas for diversifying or modifying future practices

Inspired by Friends: Adolescents' Network Homophily Moderates the Relationship between Social Comparison, Envy, and Inspiration on Instagram

© Copyright 2019, Mary Ann Liebert, Inc. Research on the negative psycho-emotional implications of social comparisons on social network sites such as Instagram has rapidly accumulated in recent years. However, little research has considered the extent to which such comparisons can elicit positive motivational outcomes for adolescent users, specifically inspiration. Furthermore, little is known about whether it matters whom young people compare themselves to on Instagram (i.e., network composition) and how this may modulate the emotional outcomes of Instagram social comparisons. The present study thus sought to determine how adolescents' Instagram comparisons of ability associate with inspiration through the mechanism of benign and malicious envy. We further examined whether two key aspects of network composition - perceived similarity and the amount of strangers followed - moderated these relationships. Results from a paper survey among n = 266 British adolescents confirm the hypothesis that those adolescents who compare more strongly on Instagram also report more inspiration from Instagram use. While benign envy positively mediated this relationship, malicious envy worked in the opposite direction, indicating the need to distinguish these two types of envy in future research. In addition, while the amount of strangers followed did not significantly affect the relationships between social comparison, envy, and inspiration, higher perceived network homophily positively moderated the relationship between social comparison and inspiration by eliciting more benign and less malicious envy. Results overall suggest that social comparisons on Instagram may be more inspiring when adolescents compare themselves to similar others and avoid unachievable false role models in their online networks

Calibration and Cross-Validation of Accelerometery for Estimating Movement Skills in Children Aged 8-12 Years

This study sought to calibrate triaxial accelerometery, worn on both wrists, waist and both ankles, during children’s physical activity (PA), with particular attention to object control motor skills performed at a fast and slow cadence, and to cross-validate the accelerometer cut-points derived from the calibration using an independent dataset. Twenty boys (10.1 ±1.5 years) undertook seven, five-minute bouts of activity lying supine, standing, running (4.5kmph−1) instep passing a football (fast and slow cadence), dribbling a football (fast and slow cadence), whilst wearing five GENEActiv accelerometers on their non-dominant and dominant wrists and ankles and waist. VO2 was assessed concurrently using indirect calorimetry. ROC curve analysis was used to generate cut-points representing sedentary, light and moderate PA. The cut-points were then cross-validated using independent data from 30 children (9.4 ± 1.4 years), who had undertaken similar activities whilst wearing accelerometers and being assessed for VO2. GENEActiv monitors were able to discriminate sedentary activity to an excellent level irrespective of wear location. For moderate PA, discrimination of activity was considered good for monitors placed on the dominant wrist, waist, non-dominant and dominant ankles but fair for the non-dominant wrist. Applying the cut-points to the cross-validation sample indicated that cut-points validated in the calibration were able to successfully discriminate sedentary behaviour and moderate PA to an excellent standard and light PA to a fair standard. Cut-points derived from this calibration demonstrate an excellent ability to discriminate children’s sedentary behaviour and moderate intensity PA comprising motor skill activity.N/

Modeling payback from research into the efficacy of left-ventricular assist devices as destination therapy

Objectives: Ongoing developments in design have improved the outlook for left-ventricular assist device (LVAD) implantation as a therapy in end-stage heart failure. Nevertheless, early cost-effectiveness assessments, based on first-generation devices, have not been encouraging. Against this background, we set out (i) to examine the survival benefit that LVADs would need to generate before they could be deemed cost-effective; (ii) to provide insight into the likelihood that this benefit will be achieved; and (iii) from the perspective of a healthcare provider, to assess the value of discovering the actual size of this benefit by means of a Bayesian value of information analysis. Methods: Cost-effectiveness assessments are made from the perspective of the healthcare provider, using current UK norms for the value of a quality-adjusted life-year (QALY). The treatment model is grounded in published analyses of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial of first-generation LVADs, translated into a UK cost setting. The prospects for patient survival with second-generation devices is assessed using Bayesian prior distributions, elicited from a group of leading clinicians in the field. Results: Using established thresholds, cost-effectiveness probabilities under these priors are found to be low (.2 percent) for devices costing as much as £60,000. Sensitivity of the conclusions to both device cost and QALY valuation is examined. Conclusions: In the event that the price of the device in use would reduce to £40,000, the value of the survival information can readily justify investment in further trials

Skin microvascular vasodilatory capacity in offspring of two parents with Type 2 diabetes

Aims<br/> Microvascular dysfunction occurs in Type 2 diabetes and in subjects with fasting hyperglycaemia. It is unclear whether this dysfunction relates to dysglycaemia. This study investigated in normogylcaemic individuals whether a genetic predisposition to diabetes, or indices of insulin resistance including endothelial markers, were associated with impaired microvascular function.<br/> Methods<br/> Maximum microvascular hyperaemia to local heating of the skin was measured using laser Doppler flowmetry in 21 normoglycaemic subjects with no family history of diabetes (Group 1) and 21 normoglycaemic age, sex and body mass index-matched offspring of two parents with Type 2 diabetes (Group 2). <br/>Results<br/> Although Group 2 had normal fasting plasma glucose and glucose tolerance tests, the 120-min glucose values were significantly higher at 6.4 (5.3-6.6) mmol/l (median (25th-75th centile)) than the control group at 4.9 (4.6-5.9) mmol/l (P=0.005) and the insulinogenic index was lower at 97.1 (60.9-130.8) vs. 124.0 (97.2-177.7) (P=0.027). Skin maximum microvascular hyperaemia (Group 1: 1.56 (1.39- 1.80) vs. Group 2: 1.53 (1.30-1.98) V, P=0.99) and minimum microvascular resistance which normalizes the hyperaemia data for blood pressure (Group 1: 52.0 (43.2-67.4) vs. Group 2: 56.0 (43.7-69.6) mmHgN, P=0.70) did not differ in the two groups. Significant positive associations occurred between minimum microvascular resistance and indices of the insulin resistance syndrome; plasminogen activator inhibitor type 1 (R-s=0.46, P=0.003), t-PA (R-s=0.36, P=0.03), total cholesterol (R-s=0.35, P=0.02), and triglyceride concentration (R-s=0.35, P=0.02), and an inverse association with insulin sensitivity (R-s=-0.33, P=0.03).<br/> Conclusions<br/> In normoglycaemic adults cutaneous microvascular vasodilatory capacity is associated with features of insulin resistance syndrome, particularly with plasminogen activator inhibitor type 1. A strong family history of Type 2 diabetes alone does not result in impairment in the maximum hyperaemic response

Occupational bladder cancer: a cross section survey of previous employments, tasks and exposures matched to cancer phenotypes

Objectives Up to 10% of Bladder Cancers may arise following occupational exposure to carcinogens. We hypothesised that different cancer phenotypes reflected different patterns of occupational exposure. Methods Consecutive participants, with bladder cancer, self-completed a structured questionnaire detailing employment, tasks, exposures, smoking, lifestyle and family history. Our primary outcome was association between cancer phenotype and occupational details. Results We collected questionnaires from 536 patients, of whom 454 (85%) participants (352 men and 102 women) were included. Women were less likely to be smokers (68% vs. 81% Chi sq. p<0.001), but more likely than men to inhale environmental tobacco smoke at home (82% vs. 74% p = 0.08) and use hair dye (56% vs. 3%, p<0.001). Contact with potential carcinogens occurred in 282 (62%) participants (mean 3.1 per worker (range 0–14)). High-grade cancer was more common than low-grade disease in workers from the steel, foundry, metal, engineering and transport industries (p<0.05), and in workers exposed to crack detection dyes, chromium, coal/oil/gas by-products, diesel fumes/fuel/aircraft fuel and solvents (such as trichloroethylene). Higher staged cancers were frequent in workers exposed to Chromium, coal products and diesel exhaust fumes/fuel (p<0.05). Various workers (e.g. exposed to diesel fuels or fumes (Cox, HR 1.97 (95% CI 1.31–2.98) p = 0.001), employed in a garage (HR 2.19 (95% CI 1.31–3.63) p = 0.001), undertaking plumbing/gas fitting/ventilation (HR 2.15 (95% CI 1.15–4.01) p = 0.017), undertaking welding (HR 1.85 (95% CI 1.24–2.77) p = 0.003) and exposed to welding materials (HR 1.92 (95% CI 1.27–2.91) p = 0.002)) were more likely to have disease progression and receive radical treatment than others. Fewer than expected deaths were seen in healthcare workers (HR 0.17 (95% CI 0.04–0.70) p = 0.014). Conclusions We identified multiple occupational tasks and contacts associated with bladder cancer. There were some associations with phenotype, although our study design precludes robust assessment

Achieving equity through 'gender autonomy': the challenges for VET policy and practice

This paper is based on research carried out in an EU Fifth Framework project on 'Gender and Qualification'. The research partners from five European countries investigated the impact of gender segregation in European labour markets on vocational education and training, with particular regard to competences and qualifications. The research explored the part played by gender in the vocational education and training experiences of (i) young adults entering specific occupations in child care, electrical engineering and food preparation/service (ii) adults changing occupations

Heterochromatic DNA Double Strand Break Repair

Eukaryotic chromatin is segregated into highly condensed heterochromatin and comparably relaxed euchromatin. Although heterochromatic gene expression is either transiently or permanently impeded, the integrity of heterochromatic DNA is critical for cell survival as it contributes to the regulation of nuclear architecture, gene expression, ribosome biogenesis, chromosome stability and mitosis. Formed by a plethora of proteins, structurally complex heterochromatin is generally inaccessible to DNA processing enzymes, including those repair factors required to rejoin DNA double strand breaks (DSBs). To be repaired, heterochromatic lesions require the Ataxia Telangiectasia Mutated (ATM) pathway to transiently modify heterochromatic factors surrounding the DSB, relaxing its structure and thereby allowing DNA non-homologous end-joining (NHEJ) to function. Cells deficient for ATM or proteins involved in its signalling cascade repair euchromatic DSBs normally but are unable to resolve lesions within heterochromatin. Depletion of key heterochromatic proteins, including the KAP-1 transcriptional co-repressor, Heterochromatin Protein 1 (HP1) or histone deacetylases 1&2 (HDAC1&2), relieves the requirement for ATM signalling in DSB repair. Importantly, KAP-1 is a highly dose dependent, transient and specific substrate of ATM and the manipulation of KAP-1 phosphorylation regulates heterochromatic DSB repair. We propose that KAP-1 is a critical heterochromatic factor that undergoes specific modifications following DSB formation to promote repair in a manner that allows localised and transient chromatin relaxation but precludes widespread dismantling of the heterochromatic superstructure

Requirement for PBAF in transcriptional repression and repair at DNA breaks in actively transcribed regions of chromatin

Actively transcribed regions of the genome are vulnerable to genomic instability. Recently, it was discovered that transcription is repressed in response to neighboring DNA double-strand breaks (DSBs). It is not known whether a failure to silence transcription flanking DSBs has any impact on DNA repair efficiency or whether chromatin remodelers contribute to the process. Here, we show that the PBAF remodeling complex is important for DSB-induced transcriptional silencing and promotes repair of a subset of DNA DSBs at early time points, which can be rescued by inhibiting transcription globally. An ATM phosphorylation site on BAF180, a PBAF subunit, is required for both processes. Furthermore, we find that subunits of the PRC1 and PRC2 polycomb group complexes are similarly required for DSB-induced silencing and promoting repair. Cancer-associated BAF180 mutants are unable to restore these functions, suggesting PBAF's role in repressing transcription near DSBs may contribute to its tumor suppressor activity