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When Flory the night fairy's wings are accidentally broken and she cannot fly, she has to learn to do everything differently.

Obesity is a common disease and a known risk factor for many other conditions such as hypertension, type 2 diabetes, and cancer. Treatment options for obesity include lifestyle changes, pharmacotherapy, and surgical interventions such as bariatric surgery. In this study, we examine the use of prescription drugs and dietary supplements by the individuals with obesity. We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) data 2003-2018. We used multivariate logistic regression to analyze the correlations of demographics and obesity status with the use of prescription drugs and dietary supplement use. We also built machine learning models to classify prescription drug and dietary supplement use using demographic data and obesity status. Individuals with obesity are more likely to take cardiovascular agents (OR = 2.095, 95% CI 1.989-2.207) and metabolic agents (OR = 1.658, 95% CI 1.573-1.748) than individuals without obesity. Gender, age, race, poverty income ratio, and insurance status are significantly correlated with dietary supplement use. The best performing model for classifying prescription drug use had the accuracy of 74.3% and the AUROC of 0.82. The best performing model for classifying dietary supplement use had the accuracy of 65.3% and the AUROC of 0.71. This study can inform clinical practice and patient education of the use of prescription drugs and dietary supplements and their correlation with obesity.

In Zero K, Don DeLillo relies on the uncanny to investigate the limits of the human condition and to bridge the tension between the transcendental and the everyday. The novel's narrator, Jeff Lockhart, offers readers a tour of the underworld in his visits to the Convergence, a cryonics facility where mannequins and frozen bodies blur the boundaries between life and death. The Convergence's promise of crystalline language, transcendent truth, and immortality is revealed to be a form of skepticism that prevents us from seeing the extraordinariness of the ordinary. An uncanny engagement with the “radiance in dailiness” allows Jeff to escape the solipsism that defines so many of DeLillo's characters and to join the community of humans, linked by finitude and solitude.

Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent edema attacks associated with morbidity and mortality. HAE results from variations in the SERPING1 gene that encodes the C1 inhibitor (C1INH), a serine protease inhibitor (serpin). Reduced plasma levels of C1INH lead to enhanced activation of the contact system, triggering high levels of bradykinin and increased vascular permeability, but the cellular mechanisms leading to low C1INH levels (20%-30% of normal) in heterozygous HAE type I patients remain obscure. Here, we showed that C1INH encoded by a subset of HAE-causing SERPING1 alleles affected secretion of normal C1INH protein in a dominant-negative fashion by triggering formation of protein-protein interactions between normal and mutant C1INH, leading to the creation of larger intracellular C1INH aggregates that were trapped in the endoplasmic reticulum (ER). Notably, intracellular aggregation of C1INH and ER abnormality were observed in fibroblasts from a heterozygous carrier of a dominant-negative SERPING1 gene variant, but the condition was ameliorated by viral delivery of the SERPING1 gene. Collectively, our data link abnormal accumulation of serpins, a hallmark of serpinopathies, with dominant-negative disease mechanisms affecting C1INH plasma levels in HAE type I patients, and may pave the way for new treatments of HAE.

(1) Background: The study examined the reliability (test–retest, intra- and inter-day) and validity of a portable 3D scanning method when quantifying human leg volume. (2) Methods: Fifteen males volunteered to participate (age, 24.6 ± 2.0 years; stature, 178.9 ± 4.5 cm; body mass, 77.4 ± 6.5 kg; mean ± standard deviation). The volume of the lower and upper legs was examined using a water displacement method (the criterion) and two consecutive 3D scans. Measurements were taken at baseline, 1 h post-baseline (intra-day) and 24 h post-baseline (inter-day). Reliability and validity of the 3D scanning method was assessed using Bland–Altman limits of agreement and Pearson’s product moment correlations. (3) Results: With respect to the test–retest reliability, the 3D scanning method had smaller systematic bias and narrower limits of agreement (±1%, and 3–5%, respectively) compared to the water displacement method (1–2% and 4–7%, respectively), when measuring lower and upper leg volume in humans. The correlation coefficients for all reliability comparisons (test–retest, intra-day, inter-day) would all be regarded as ‘very strong’ (all 0.94 or greater). (4) Conclusions: The study’s results suggest that a 3D scanning method is a reliable and valid method to quantify leg volume.

This study’s aim was to assess FreeStyle Libre Flash glucose monitoring (FGM) performance during an oral glucose tolerance test (OGTT) and treadmill exercise in healthy adolescents. This should advance the feasibility and utility of user-friendly technologies for metabolic assessments in adolescents. Seventeen healthy adolescents (nine girls aged 12.8 ± 0.9 years) performed an OGTT and submaximal and maximal treadmill exercise tests in a laboratory setting. The scanned interstitial fluid glucose concentration ([ISFG]) obtained by FGM was compared against finger-prick capillary plasma glucose concentration ([CPG]) at 0 (pre-OGTT), −15, −30, −60, −120 min post-OGTT, pre-, mid-, post- submaximal exercise, and pre- and post- maximal exercise. Overall mean absolute relative difference (MARD) was 13.1 ± 8.5%, and 68% (n = 113) of the paired glucose data met the ISO 15197:2013 criteria. For clinical accuracy, 84% and 16% of FGM readings were within zones A and B in the Consensus Error Grid (CEG), respectively, which met the ISO 15197:2013 criteria of having at least 99% of results within these zones. Scanned [ISFG] were statistically lower than [CPG] at 15 (−1.16 mmol∙L−1, p < 0.001) and 30 min (−0.74 mmol∙L−1, p = 0.041) post-OGTT. Yet, post-OGTT glycaemic responses assessed by total and incremental areas under the curve (AUCs) were not significantly different, with trivial to small effect sizes (p ≥ 0.084, d = 0.14–0.45). Further, [ISFGs] were not different from [CPGs] during submaximal and maximal exercise tests (interaction p ≥ 0.614). FGM can be a feasible alternative to reflect postprandial glycaemia (AUCs) in healthy adolescents who may not endure repeated finger pricks.

Objective: The purpose of this study was to compare two pedagogical methods, active learning and passive instruction, to determine which is more useful in helping students to achieve the learning outcomes in a one-hour research skills instructional session.Methods: Two groups of high school students attended an instructional session to learn about consumer health resources and strategies to enhance their searching skills. The first group received passive instruction, and the second engaged in active learning. We assessed both groups’ learning using 2 methods with differing complexity. A total of 59 students attended the instructional sessions (passive instruction, n=28; active learning, n=31).Results: We found that the active learning group scored more favorably in four assessment categories.Conclusions: Active learning may help students engage with and develop a meaningful understanding of several resources in a single session. Moreover, when using a complex teaching strategy, librarians should be mindful to gauge learning using an equally complex assessment method.

The study examined whether the performance characteristics of male university field hockey players differed when the match format was 2 × 35 min halves compared to 2 × 2 × 17.5 min quarters. Thirty-five male university field hockey players (age 21.2 ± 3.0 years, height 1.81 ± 0.07 m, body mass 75.1 ± 8.9 kg), competing at national level in the UK, were monitored over 52 matches played across the 2018–2019 (2 × 35 min halves) and 2019–2020 (2 × 2 × 17.5 min quarters) seasons using 15 Hz Global Positioning System units and heart rate monitors. Total distance, high-speed running distance (≥15.5 km·h−1), accelerations (≥2 m·s−1), decelerations (≤−2 m·s−1), average heart rate and percentage of time spent at >85% of maximum heart rate were recorded during both match formats. Two-level random intercept hierarchal models (Match—level 1, Player—level 2) suggested that the change in format from 2 × 35 min halves (2018–2019 season) to 2 × 2 × 17.5 min quarters (2019–2020 season) resulted in a reduction in total distance and high-speed running distance completed during a match (by 221 m and 120 m, respectively, both p < 0.001). As no significant cross-level interactions were observed (between season and half), the change from 35 min halves to 17.5 min quarters did not attenuate the reduced physical performance evident during the second half of matches (total distance: −235 m less in second half; high-speed running distance: −70 m less in second half; both p < 0.001). Overall, the findings suggest that the change in match format did alter the performance characteristics of male university field hockey players, but the quarter format actually reduced the total distance and high-speed running distance completed during matches, and did not attenuate the reduction in performance seen during the second half of matches.

Background Despite recent improvements, there is still stark inequity in the funding and provision of 24/7 end-of-life care for children, resulting in many families not receiving the support they need. To inform, plan and implement service changes it is important to take account of what works in current contexts and existing models of care, and to learn how professionals ‘on the ground’ are currently experiencing 24/7 care delivery. Methods The study aimed to explore professionals’ perspectives of delivering 24/7 paediatric palliative care and their expectations and needs of a new service. This qualitative study used focus groups, and a thematic framework approach to analyse the data. Participants were healthcare professionals (HCPs) involved in the delivery of care to children (0–18 years) with palliative care needs and their families. Results Fifty-three healthcare professionals, (25 doctors, 19 nurses, 6 managerial/administration and 3 allied professionals), took part in 11 focus groups. Three themes with sub-themes were developed: (1) Working within a fragmented landscape (Responding to the need for 24/7 end-of-life care, Coordination across teams without infrastructure, Building 24/7 continuity through integration); (2) Constraints on choice: default not preferred choice? (Limits to family choice, Critical yet inconsistent provision of community nursing, Inequality of access to specialist support); and (3) The personal cost of making it work (Gaps in confidence and experience, The price of goodwill). Professionals navigated a disjointed system to deliver 24/7 care to families. They strived to offer care in families’ preferred place; however, choice was constrained by the availability of local services. Professionals stretched themselves to provide around the clock care, often sacrificing their personal wellbeing and in doing so, inadvertently sustaining a broken system. Conclusion Stepping up to support families with 24/7 end-of-life care for their child, has resulted in an unsustainable physical and emotional toll on professionals. The impact of delivering care in an inequitable system is causing significant moral distress, and there is a growing realisation that their goodwill is masking current systemic shortcomings. Integrated Care Boards must work jointly to find economies of scale to establish equitable and sustainable models of delivery that meet national standards and to ensure all children have access to high quality 24/7 end-of-life care. Key statements What is already known about this topic? • Providing 24/7 access to professionals with palliative care knowledge is key to supporting children and their families receiving end-of-life care in their preferred place, however there is stark inequity in funding and provision, resulting in many children and their families not receiving the care they need. What this study adds • Regional service variations meant professionals were reactively finding ad hoc solutions for families; without supporting infrastructure in place, it takes time and resources to coordinate 24/7 end-of-life care across multiple teams. • Professionals experienced moral distress when inequality in service provision constrained their ability to offer some families choice of place of end-of-life care.  • The study showed that sustaining 24/7 end-of-life care often relied on the goodwill of overstretched professionals leading to emotional and physical strain and concerns their efforts were masking systemic shortcomings. How this study might affect research, practice or policy • ICBs need to work jointly to develop equitable and sustainable models of 24/7 end-of-life care to meet statutory duties and to ensure all children have access to high-quality care at the end of their lives.

Background Providing high quality around-the-clock care, is key to supporting families in their preferred place of care. Changing symptoms and parents’ distress cannot wait for ‘opening hours’. Yet in the UK, 24/7 children’s end-of-life care remains a significant postcode lottery. To inform equitable service development this study explored parents’ experiences accessing 24/7 paediatric palliative care, their expectations and needs. Methods Qualitative study using in-depth interviews, analysed using thematic analysis. Parents in one region of England, were eligible if their child had a life-limiting condition and end-of-life care was planned, or if they were bereaved parents whose child had died within the previous 3–36 months. Results Twenty-six parents were interviewed, 13 currently caring for their child and 13 bereaved parents. Two themes were developed: “Scaffolded for uncertainty and crisis” and “Falling through the service gaps”. Most parents want seamless 24/7 end-of-life care for their child at home and to avoid hospital admissions. Despite being desperate to be home and feeling unsafe in hospital, service gaps mean, for some families, there is no option other than their child dying as an inpatient. Conclusion The study found marked inequity in parent’s experiences. Parents are confident when supported by a trusted 24/7 team with experience delivering palliative care, that provides phone support, face-to-face nursing and access to specialist advice. Hospital staff need improved training and consistent support from specialist palliative care teams. Further research with professionals is needed to understand the local and regional barriers that are preventing this support being available to all families.