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BackgroundA balanced approach toward sun exposure and protection is needed by young people. Excessive sun exposure increases their risk for skin cancers such as melanoma, whereas some exposure is necessary for vitamin D and healthy bones. We have developed a new iOS smartphone app—Sun Safe—through a co-design process, which aims to support healthy and balanced decision-making by young teenagers (aged 12-13 years). ObjectiveThe aim of this study was to test the capacity of Sun Safe to improve sun health knowledge and behaviors of young teenagers in 3 pilot intervention studies completed in 2020. MethodsYoung teenagers (aged 12-13 years; N=57) were recruited through the web or through a local school via an open-access website and given access to Sun Safe (29/57, 51%) or a placebo (SunDial) app (28/57, 49%). Participants completed sun health questionnaires and knowledge quizzes before and after the 6-week intervention (either on the web or in class) and rated the quality of the app they used via a survey. ResultsOf the 57 participants, 51 (89%) participants (26, 51% for placebo arm and 25, 49% for the Sun Safe arm) completed these studies, with most (>50%) reporting that they used a smartphone to access their designated app either “once a fortnight” or “once/twice in total.” Improved sun health knowledge—particularly about the UV Index—was observed in participants who were given access to Sun Safe compared with those who used the placebo (−6.2 [percentage correct] difference in predicted means, 95% CI –12.4 to –0.03; P=.049; 2-way ANOVA). Unexpectedly, there were significantly more sunburn events in the Sun Safe group (relative risk 1.7, 95% CI 1.1-1.8; P=.02; Fisher exact test), although no differences in time spent outdoors or sun-protective behaviors were reported. COVID-19 pandemic–related community-wide shutdowns during April 2020 (when schools were closed) reduced the time spent outdoors by >100 minutes per day (–105 minutes per day difference in predicted means, 95% CI –150 to –59 minutes per day; P=.002; paired 2-tailed Student t test). Sun Safe was well-rated by participants, particularly for information (mean 4.2, SD 0.6 out of 5). ConclusionsAccess to the Sun Safe app increased sun health knowledge among young teenagers in these pilot intervention studies. Further investigations with larger sample sizes are required to confirm these observations and further test the effects of Sun Safe on sun-protective behaviors.

We present a healthy adolescent male with no past surgical history who presented with acute onset abdominal pain. Cross-sectional imaging was concerning for possible ileocecal intussusception, and repeat imaging demonstrated an internal hernia. The patient was taken to the operating room for exploration. He was discovered to have an ileocecal intussusception with a large cecal mass, as well as a left paraduodenal hernia. Closure of the mesenteric defect and ileocecectomy with primary anastomosis were performed. Pathology of the mass was consistent with colonic lipoma. Postoperatively, he had slow return of bowel function, but his recovery was otherwise uncomplicated. This case reports a rare presentation of concomitant ileocecal intussusception due to a cecal lipoma and congenital internal hernia. Intussusception in the pediatric population is typically idiopathic, and intussusception with a pathologic lead point is far more common in adults. Gastrointestinal lipomas are also uncommon in pediatric patients, and when discovered are generally small and asymptomatic. Internal hernias most commonly are due to acquired mesenteric defects or adhesive disease, though may present congenitally as seen in this patient. This case is unique because of the simultaneous occurrence of two separate surgical problems, both with atypical etiologies based on patient history and demographics.

Abstract Background Recent changes in communication technologies, including increased reliance on mobile phones and the internet, may present challenges and/or opportunities to re-engaging inactive study cohorts. We evaluate our ability to recruit participants for the Kidskin Young Adult Myopia Study (KYAMS), a follow-up of the Kidskin Study. Methods KYAMS participants were recruited from the Kidskin Study, a sun exposure-intervention study for 5–6 year-olds running from 1995 to 1999 with most recent follow-up in 2005. From 2015 to 2019, the KYAMS used mail-outs, phone calls and social media to contact Kidskin Study participants. Multivariable logistic regression was used to identify variables associated with successful contact of a Kidskin Study participant or family member and KYAMS participation. Results Of 1695 eligible participants, 599 (35.5%) participants (or a family member) were contacted and 303 (17.9%) participated in the KYAMS. KYAMS participation was more likely in those who participated in the 2005 follow-up (odds ratio [OR] = 5.09, 95% confidence interval [CI]: 3.67–7.06) and had a mobile phone number on record (OR = 2.25, CI: 1.57–3.23). Of those contacted, participants who were the first point of contact (OR = 4.84, CI: 2.89–8.10) and who were contacted by letter in the first (OR = 6.53, CI: 3.35–12.75) or second (OR = 5.77, CI: 2.85–11.67) round were more likely to participate in the KYAMS, compared to contact by landline phone. Conclusions We recruited approximately one-fifth of Kidskin Study participants for the KYAMS. Participants were more likely to participate in the KYAMS if they were contacted directly, rather than through a family member, and if they were contacted by invitation letter. Trial registration ACTRN12617000812392 .

The recent discovery of an upper limit in the tolerance of an extremotolerant tardigrade to high temperatures is astounding. Although these microinvertebrates are able to endure severe environmental conditions, including desiccation, freezing and high levels of radiation, high temperatures seem to be an Achilles’ heel for active tardigrades. Moreover, exposure-time appears to be a limiting factor for the heat stress tolerance of the otherwise highly resilient desiccated (anhydrobiotic) tardigrades. Indeed, the survival rate of desiccated tardigrades exposed to high temperatures for 24 hours is significantly lower than for exposures of only 1 hour. Here, we investigate the effect of 1 week of high temperature exposures on desiccated tardigrades with the aim of elucidating whether exposure-times longer than 24 hours decrease survival even further. From our analyses we estimate a significant decrease in the 50% mortality temperature from 63ºC to 56ºC for Ramazzottius varieornatus exposed to high temperatures in the desiccated tun state for 24 hours and 1 week, respectively. This negative correlation between exposure-time and tolerance to high temperatures probably results from the interference of intracellular temperature with the homeostasis of macromolecules. We hypothesize that high temperatures denature molecules that play a vital role in sustaining and protecting the anhydrobiotic state.

Abstract Objective To determine whether serum neurofilament light chain (sNfL) levels are suppressed in patients with the clinically isolated syndrome (CIS) following narrowband ultraviolet B phototherapy (UVB‐PT). Methods sNfL levels were measured using a sensitive single‐molecule array assay at baseline and up to 12 months in 17 patients with CIS, 10 of whom received UVB‐PT, and were compared with healthy control (HC) and early relapsing remitting multiple sclerosis (RRMS) group. sNfL levels were correlated with magnetic resonance imaging total lesion volume (LV) determined using icobrain version 4.4.1 and with clinical outcomes. Results Baseline median sNfL levels were significantly higher in the CIS (20.6 pg/mL, interquartile range [IQR] 13.7–161.4) and RRMS groups (36.6 pg/ml [IQR] 16.2–212.2) than in HC (10.7 pg/ml [IQR] 4.9–21.5) (p = .012 and p = .0002, respectively), and were strongly correlated with T2 and T1 LV at 12 months (r = .800; p = .014 and r = .833; p = .008, respectively) in the CIS group. Analysis of changes in sNfL levels over time in the CIS group showed a significant cumulative suppressive effect of UVB‐PT in the first 3 months (UVB‐PT −10.6% vs non‐UVB‐PT +58.3%; p = .04) following which the levels in the two groups converged and continued to fall. Conclusions Our findings provide the basis for further studies to determine the utility of sNfL levels as a marker of neuro‐axonal damage in CIS and early MS and for assessing the efficacy of new therapeutic interventions such as UVB‐PT.

Background: In its severest form, non-accidental injury (NAI) in children is fatal. South Africa has been reported to have double the global average of child homicides. Autopsy is the main investigation in fatal NAI with post-mortem skeletal surveys (PMSS) playing an adjunctive role. Whilst fracture patterns associated with NAI in living patients have been established, this has not been investigated in PMSS in South Africa. Objectives: To determine the incidence and characteristics of fractures in suspected fatal NAI cases. To calculate the incidence of fractures according to high-, moderate- and low-specificity fracture locations for NAI. Methods: A retrospective review of all PMSS performed between 01 January 2012 and 03 December 2018 was conducted at the Charlotte Maxeke Johannesburg Academic Hospital. Results: Of the 73 PMSS, 33 (45.2%) demonstrated fractures. No statistical significance in sex was found: 38 (52.1%) were male and 35 (47.9%) were female (p 0.05). The mean age of those who sustained fractures was 28 months (standard deviation [s.d.]: 21 months). A total of 115 fractures were sustained, of that the top five bones fractured were the ribs 37 (32.2%), parietal bone 13 (11.3%), ulna 13 (11.3%), femur 13 (11.3%), and radius 11 (9.6%). High-specificity fracture locations accounted for 40/133 (30.1%). Conclusion: The fracture types in PMSS were similar to those in live skeletal surveys. Our study’s fracture rate was higher in comparison to international studies. The PMSS is a valuable adjunct to autopsy in detecting occult fractures of the limbs. We recommend that PMSS be performed in suspected fatal NAI cases at least in children up to 24 months of age.

Abstract Background People experiencing homelessness are known to suffer from poor health and can be reluctant to seek healthcare except in crisis. Foot and ankle problems are a concern; as well as causing discomfort and pain, they may escalate from a minor problem to a very serious one without timely and appropriate treatment. Little is known about the foot and ankle problems of people experiencing homelessness. This paper describes a podiatric service specifically for people experiencing homelessness, which includes a fixed site as well as outreach services. The service operates as part of the Homelessness Team program at Cohealth, a large community health service in Melbourne. Methods The study used routinely collected data. Every person who was seen by the podiatrist in the Cohealth Homelessness Team in 2019, whether on site or on outreach, was included in the study (n = 295). Of these, 156 were attending for the first time and 139 were returning clients. People who used the service were predominantly rough sleeping (45.2%), with 32.2% in unstable or insecure housing and 22.6% recently housed. Results Skin and nail pathologies (68.1%), inadequate footwear (51.9%) and biomechanical issues (44.1%) were the most common presentations. People sleeping rough were particularly likely to present with biomechanical issues (50.8%), acute wound care needs (17.4%) or traumatic injury (10.6%). Most people presented with more than one issue (mean = 2.4), and new clients (mean = 2.53) and those rough sleeping (mean = 2.69) had more issues than others. Outreach was the most effective way to reach clients in the most difficult circumstances (48.9% of those in unstable housing, 34.8% of rough sleepers). Most of the clients (81.4%) had connections with other services offered by Cohealth, such as social work or physiotherapy. Conclusions This study demonstrated that reaching and intervening on foot and ankle problems of people experiencing homelessness who may not seek care on their own could be achieved through a publicly funded health service, using simplified pathways to care including outreach. In addition to the long‐ and short‐ term benefits of the immediate podiatric treatment, building trust and connections through footcare may provide an entry point into accepting other health and welfare services.

Dysferlinopathies are a clinically heterogeneous group of muscular dystrophies caused by a genetic deficiency of the membrane-associated protein dysferlin, which usually manifest post-growth in young adults. The disease is characterized by progressive skeletal muscle wasting in the limb-girdle and limbs, inflammation, accumulation of lipid droplets in slow-twitch myofibers and, in later stages, replacement of muscles by adipose tissue. Previously we reported myofiber-type specific differences in muscle contractile function of 10-month-old dysferlin-deficient BLAJ mice that could not be fully accounted for by altered myofiber-type composition. In order to further investigate these findings, we examined the impact of dysferlin deficiency on the abundance of calcium (Ca2+) handling and glucose/glycogen metabolism-related proteins in predominantly slow-twitch, oxidative soleus and fast-twitch, glycolytic extensor digitorum longus (EDL) muscles of 10-month-old wild-type (WT) C57BL/6J and dysferlin-deficient BLAJ male mice. Additionally, we compared the Ca2+ activation properties of isolated slow- and fast-twitch myofibers from 3-month-old WT and BLAJ male mice. Differences were observed for some Ca2+ handling and glucose/glycogen metabolism-related protein levels between BLAJ soleus and EDL muscles (compared with WT) that may contribute to the previously reported differences in function in these BLAJ muscles. Dysferlin deficiency did not impact glycogen content of whole muscles nor Ca2+ activation of the myofilaments, although soleus muscle from 10-month-old BLAJ mice had more glycogen than EDL muscles. These results demonstrate a further impact of dysferlin deficiency on proteins associated with excitation-contraction coupling and glycogen metabolism in skeletal muscles, potentially contributing to altered contractile function in dysferlinopathy.

Biomolecular ocean observing and research is a rapidly evolving field that uses omics approaches to describe biodiversity at its foundational level, giving insight into the structure and function of marine ecosystems over time and space. It is an especially effective approach for investigating the marine microbiome. To mature marine microbiome research and operations within a global ocean biomolecular observing network (OBON) for the UN Decade of Ocean Science for Sustainable Development and beyond, research groups will need a system to effectively share, discover, and compare “omic” practices and protocols. While numerous informatic tools and standards exist, there is currently no global, publicly-supported platform specifically designed for sharing marine omics [or any omics] protocols across the entire value-chain from initiating a study to the publication and use of its results. Toward that goal, we propose the development of the Minimum Information for an Omic Protocol (MIOP), a community-developed guide of curated, standardized metadata tags and categories that will orient protocols in the value-chain for the facilitated, structured, and user-driven discovery of suitable protocol suites on the Ocean Best Practices System. Users can annotate their protocols with these tags, or use them as search criteria to find appropriate protocols. Implementing such a curated repository is an essential step toward establishing best practices. Sharing protocols and encouraging comparisons through this repository will be the first steps toward designing a decision tree to guide users to community endorsed best practices.

Approximately 85% of tuberculosis (TB) related deaths occur in low- and middle-income countries where health resources are scarce. Effective priority setting is required to maximise the impact of limited budgets. The Optima TB tool has been developed to support analytical capacity and inform evidence-based priority setting processes for TB health benefits package design. This paper outlines the Optima TB framework and how it was applied in Belarus, an upper-middle income country in Eastern Europe with a relatively high burden of TB. Optima TB is a population-based disease transmission model, with programmatic cost functions and an optimisation algorithm. Modelled populations include age-differentiated general populations and higher-risk populations such as people living with HIV. Populations and prospective interventions are defined in consultation with local stakeholders. In partnership with the latter, demographic, epidemiological, programmatic, as well as cost and spending data for these populations and interventions are then collated. An optimisation analysis of TB spending was conducted in Belarus, using program objectives and constraints defined in collaboration with local stakeholders, which included experts, decision makers, funders and organisations involved in service delivery, support and technical assistance. These analyses show that it is possible to improve health impact by redistributing current TB spending in Belarus. Specifically, shifting funding from inpatient- to outpatient-focused care models, and from mass screening to active case finding strategies, could reduce TB prevalence and mortality by up to 45% and 50%, respectively, by 2035. In addition, an optimised allocation of TB spending could lead to a reduction in drug-resistant TB infections by 40% over this period. This would support progress towards national TB targets without additional financial resources. The case study in Belarus demonstrates how reallocations of spending across existing and new interventions could have a substantial impact on TB outcomes. This highlights the potential for Optima TB and similar modelling tools to support evidence-based priority setting.

Objective: Emotional eating (EE) is prevalent in people seeking obesity treatment and is a contributor to poor weight loss outcomes. We aimed to delineate the emotions most associated with this type of eating, and whether they differ by sex in people undergoing obesity treatment. Methods: A cross-sectional study recruiting 387 adults from a hospital obesity management service. Emotional eating was measured using the Emotional Eating Scale (EES). Separate analyses included all participants, and those undergoing lifestyle interventions alone or in combination with obesity medication and/or bariatric surgery. Results: A total of 387 people (71% women) participated in the study (n = 187 receiving lifestyle modification alone; n = 200 in combination with additional treatments). Feeling ‘bored’ was most commonly and most strongly associated with the urge to eat, regardless of sex or treatment. Women had higher scores for total EES, for subscales of depression and anger, and individual feelings of ‘blue’, ‘sad’ and ‘upset’ compared to men. Conclusions: Understanding why certain emotions differentially trigger an urge to eat in men and women, and finding strategies to break the link between boredom and eating may enable better personalisation of lifestyle interventions for people with obesity.

Germline heterozygous PTEN mutations have been associated with high prevalence of autism spectrum disorder (ASD) and elevated rates and severity of broadly defined behavioral problems. However, limited progress has been made toward understanding whether PTEN mutation is associated with specific psychiatric co-morbidity profiles when compared to idiopathic ASD. The current study aimed to utilize a cross-measure approach to compare concurrent psychiatric characteristics across children and adolescents with PTEN mutation with (PTEN-ASD; n = 38) and without ASD (PTEN-No ASD; n = 23), and ASD with macrocephaly but no PTEN mutation (macro-ASD; n = 25) using the Child Behavior Checklist (CBCL) and the Aberrant Behavior Checklist (ABC). There were significant group effects for the CBCL Internalizing and Externalizing broad symptom score, the majority of specific CBCL syndrome scores, and all ABC subscale scores. Post-hoc comparisons revealed greater behavioral symptoms in the ASD groups (PTEN-ASD and macro-ASD) compared to the PTEN-no ASD group on nearly all subtest scores examined. There were no statistically significant differences between the PTEN-ASD and macro-ASD groups; however, there was a trend for the macro-ASD group showing higher levels of aggressive behaviors. Our findings provide evidence of specific behavior profiles across PTEN-No ASD, PTEN-ASD, and macro-ASD groups and highlight the importance of early identification of behavioral vulnerabilities in individuals with PTEN mutations in order to provide access to appropriate evidence-based interventions.

Summary: Background: Vietnam has emerged as one of the world's leading success stories in responding to COVID-19. After a prolonged period of little to no transmission, there was an outbreak of unknown source in July, 2020, in the Da Nang region, but the outbreak was quickly suppressed. We aimed to use epidemiological, behavioural, demographic, and policy data from the COVID-19 outbreak in Da Nang to calibrate an agent-based model of COVID-19 transmission for Vietnam, and to estimate the risk of future outbreaks associated with reopening of international borders in the country. Methods: For this modelling study, we used comprehensive data from June 15 to Oct 15, 2020, on testing, COVID-19 cases, and quarantine breaches within an agent-based model of SARS-CoV-2 transmission to model a COVID-19 outbreak in Da Nang in July, 2020. We applied this model to quantify the risk of future outbreaks in Vietnam in the 3 months after the reopening of international borders, under different behavioural scenarios, policy responses (ie, closure of workplaces and schools), and ongoing testing. Findings: We estimated that the outbreak in Da Nang between July and August, 2020, resulted in substantial community transmission, and that higher levels of symptomatic testing could have mitigated this transmission. We estimated that the outbreak peaked on Aug 2, 2020, with an estimated 1060 active infections (95% projection interval 890–1280). If the population of Vietnam remains highly compliant with mask-wearing policies, our projections indicate that the epidemic would remain under control even if a small but steady flow of imported infections escaped quarantine into the community. However, if complacency increases and testing rates are relatively low (10% of symptomatic individuals are tested), the epidemic could rebound again, resulting in an estimated 2100 infections (95% projected interval 1050–3610) in 3 months. These outcomes could be mitigated if the behaviour of the general population responds dynamically to increases in locally acquired cases that exceed specific thresholds, but only if testing of symptomatic individuals is also increased. Interpretation: The successful response to COVID-19 in Vietnam could be improved even further with higher levels of symptomatic testing. If the previous approaches are used in response to new COVID-19 outbreaks, epidemic control is possible even in the presence of low levels of imported cases. Funding: Ministry of Science and Technology (Vietnam). Translation: For the Vietnamese translation of the abstract see Supplementary Materials section.

The COVID-19 pandemic has created an urgent need for models that can project epidemic trends, explore intervention scenarios, and estimate resource needs. Here we describe the methodology of Covasim (COVID-19 Agent-based Simulator), an open-source model developed to help address these questions. Covasim includes country-specific demographic information on age structure and population size; realistic transmission networks in different social layers, including households, schools, workplaces, long-term care facilities, and communities; age-specific disease outcomes; and intrahost viral dynamics, including viral-load-based transmissibility. Covasim also supports an extensive set of interventions, including non-pharmaceutical interventions, such as physical distancing and protective equipment; pharmaceutical interventions, including vaccination; and testing interventions, such as symptomatic and asymptomatic testing, isolation, contact tracing, and quarantine. These interventions can incorporate the effects of delays, loss-to-follow-up, micro-targeting, and other factors. Implemented in pure Python, Covasim has been designed with equal emphasis on performance, ease of use, and flexibility: realistic and highly customized scenarios can be run on a standard laptop in under a minute. In collaboration with local health agencies and policymakers, Covasim has already been applied to examine epidemic dynamics and inform policy decisions in more than a dozen countries in Africa, Asia-Pacific, Europe, and North America.

The consequences of blast exposure (including both high-level and low-level blast) have been a focal point of military interest and research for years. Recent mandates from Congress (e.g., National Defense Authorization Act for Fiscal Year 2018, section 734) have further accelerated these efforts, facilitating collaborations between research teams from a variety of disciplinary backgrounds. Based on findings from a recent scoping review, we argue that the scientific field of blast research is plagued by inconsistencies in both conceptualization of relevant constructs and terminology used to describe them. These issues hamper our ability to interpret study methods and findings, hinder efforts to integrate findings across studies to reach scientific consensus, and increase the likelihood of redundant efforts. We argue that multidisciplinary experts in this field require a universal language and clear, standardized terminology to further advance the important work of examining the effects of blast exposure on human health, performance, and well-being. To this end, we present a summary of descriptive conventions regarding the language scientists currently use when discussing blast-related exposures and outcomes based on findings from a recent scoping review. We then provide prescriptive conventions about how these terms should be used by clearly conceptualizing and explicitly defining relevant constructs. Specifically, we summarize essential concepts relevant to the study of blast, precisely distinguish between high-level blast and low-level blast, and discuss how the terms acute, chronic, exposure, and outcome should be used when referring to the health-related consequences of blast exposure.

Abstract Background Health resources are limited, which means spending should be focused on the people, places and programs that matter most. Choosing the mix of programs to maximize a health outcome is termed allocative efficiency. Here, we extend the methodology of allocative efficiency to answer the question of how resources should be distributed among different geographic regions. Methods We describe a novel geographical optimization algorithm, which has been implemented as an extension to the Optima HIV model. This algorithm identifies an optimal funding of services and programs across regions, such as multiple countries or multiple districts within a country. The algorithm consists of three steps: (1) calibrating the model to each region, (2) determining the optimal allocation for each region across a range of different budget levels, and (3) finding the budget level in each region that minimizes the outcome (such as reducing new HIV infections and/or HIV-related deaths), subject to the constraint of fixed total budget across all regions. As a case study, we applied this method to determine an illustrative allocation of HIV program funding across three representative oblasts (regions) in Ukraine (Mykolayiv, Poltava, and Zhytomyr) to minimize the number of new HIV infections. Results Geographical optimization was found to identify solutions with better outcomes than would be possible by considering region-specific allocations alone. In the case of Ukraine, prior to optimization (i.e. with status quo spending), a total of 244,000 HIV-related disability-adjusted life years (DALYs) were estimated to occur from 2016 to 2030 across the three oblasts. With optimization within (but not between) oblasts, this was estimated to be reduced to 181,000. With geographical optimization (i.e., allowing reallocation of funds between oblasts), this was estimated to be further reduced to 173,000. Conclusions With the increasing availability of region- and even facility-level data, geographical optimization is likely to play an increasingly important role in health economic decision making. Although the largest gains are typically due to reallocating resources to the most effective interventions, especially treatment, further gains can be achieved by optimally reallocating resources between regions. Finally, the methods described here are not restricted to geographical optimization, and can be applied to other problems where competing resources need to be allocated with constraints, such as between diseases.

In this paper, we present the initial changes and continuing challenges that are faced by teachers and students due to the unexpected transition to online learning from the COVID-19 pandemic at Bahir Dar University, Ethiopia. For this, the authors applied a phenomenological-case-study design, collecting qualitative data from purposively selected Ph.D. students (n = 10) and teachers (n = 4), examiners (n = 2), as well as the postgraduate coordinator. The results indicate that the teachers experienced some difficulties in effectively using learning technologies. Moreover, the students were overburdened with increased accountability and excessive challenges. However, the institutional capacity to support was relatively minimal. Despite these odds, the study participants showed higher levels of willingness and completed the program successfully. The study participants reported moderate satisfaction with their personal and professional experiences. The COVID-19 pandemic is an opportunity to remind universities and colleges about the essential skills that students need in this unpredictable world, for example, informed decision making, creative problem solving, and adaptability.

Teacher questions have long been considered important in mediating students’ learning in language classrooms. This paper examined the mediated-learning behaviors involved in teacher questions during whole-class instruction in high schools of China. Five lessons of different topics were observed. Conversation analytic approach was applied to analyze teachers’ verbal interactions with students during whole-class teaching. Teachers’ questions and students’ responses were transcribed and categorized as display questions or referential questions. The mediated-learning behaviors involved in the two types of questions were discussed by presenting six sessions of interaction. The study investigated which question type initiated the interaction involving more variety of mediated-learning behaviors and what pedagogical implications this may have for teacher questioning techniques that enhance student learning. The study found the interactions initiated by referential questions contain more varieties of mediated-learning behaviors. This study suggests that teachers need to be encouraged to use referential questions more frequently whether in display interactions or in referential interactions.

Objectives The early stages of the COVID-19 pandemic illustrated that SARS-CoV-2, the virus that causes the disease, has the potential to spread exponentially. Therefore, as long as a substantial proportion of the population remains susceptible to infection, the potential for new epidemic waves persists even in settings with low numbers of active COVID-19 infections, unless sufficient countermeasures are in place. We aim to quantify vulnerability to resurgences in COVID-19 transmission under variations in the levels of testing, tracing and mask usage.Setting The Australian state of New South Wales (NSW), a setting with prolonged low transmission, high mobility, non-universal mask usage and a well-functioning test-and-trace system.Participants None (simulation study).Results We find that the relative impact of masks is greatest when testing and tracing rates are lower and vice versa. Scenarios with very high testing rates (90% of people with symptoms, plus 90% of people with a known history of contact with a confirmed case) were estimated to lead to a robustly controlled epidemic. However, across comparable levels of mask uptake and contact tracing, the number of infections over this period was projected to be 2–3 times higher if the testing rate was 80% instead of 90%, 8–12 times higher if the testing rate was 65% or 30–50 times higher with a 50% testing rate. In reality, NSW diagnosed 254 locally acquired cases over this period, an outcome that had a moderate probability in the model (10%–18%) assuming low mask uptake (0%–25%), even in the presence of extremely high testing (90%) and near-perfect community contact tracing (75%–100%), and a considerably higher probability if testing or tracing were at lower levels.Conclusions Our work suggests that testing, tracing and masks can all be effective means of controlling transmission. A multifaceted strategy that combines all three, alongside continued hygiene and distancing protocols, is likely to be the most robust means of controlling transmission of SARS-CoV-2.

Although blast exposure has been recognized as a significant source of morbidity and mortality in military populations, our understanding of the effects of blast exposure, particularly low-level blast (LLB) exposure, on health outcomes remains limited. This scoping review provides a comprehensive, accessible review of the peer-reviewed literature that has been published on blast exposure over the past two decades, with specific emphasis on LLB. We conducted a comprehensive scoping review of the scientific literature published between January 2000 and 2019 pertaining to the effects of blast injury and/or exposure on human and animal health. A three-level review process with specific inclusion and exclusion criteria was used. A full-text review of all articles pertaining to LLB exposure was conducted and relevant study characteristics were extracted. The research team identified 3,215 blast-relevant articles, approximately half of which (55.4%) studied live humans, 16% studied animals, and the remainder were non-subjects research (e.g., literature reviews). Nearly all (99.49%) of the included studies were conducted by experts in medicine or epidemiology; approximately half of these articles were categorized into more than one medical specialty. Among the 51 articles identified as pertaining to LLB specifically, 45.1% were conducted on animals and 39.2% focused on human subjects. Animal studies of LLB predominately used shock tubes to induce various blast exposures in rats, assessed a variety of outcomes, and clearly demonstrated that LLB exposure is associated with brain injury. In contrast, the majority of LLB studies on humans were conducted among military and law enforcement personnel in training environments and had remarkable variability in the exposures and outcomes assessed. While findings suggest that there is the potential for LLB to harm human populations, findings are mixed and more research is needed. Although it is clear that more research is needed on this rapidly growing topic, this review highlights the detrimental effects of LLB on the health of both animals and humans. Future research would benefit from multidisciplinary collaboration, larger sample sizes, and standardization of terminology, exposures, and outcomes.

This randomized, double-blind controlled trial of everolimus in individuals with germline phosphatase and tensin homolog mutations (PTEN) was designed to evaluate the safety of everolimus compared with placebo and to evaluate the efficacy of everolimus on neurocognition and behavior compared to placebo as measured by standardized neurocognitive and motor measures as well as behavioral questionnaires. The safety profile of everolimus is characterized by manageable adverse events that are generally reversible and non-cumulative. The primary safety endpoint of this study was drop-out rate due to side effects, comparing everolimus versus placebo. We also sought to determine the frequency of adverse events by type and severity. The main efficacy endpoint was a neurocognitive composite computed in two ways: 1) an average for working memory, processing speed, and fine motor subtests; and 2) the same average as above except weighted 2/3, and an additional average based on all other available neurocognitive testing measures assessing the additional domains of nonverbal ability, visuomotor skills, verbal learning, and receptive and expressive language, weighted 1/3. Secondary efficacy endpoints examined the effect of everolimus on overall global clinical improvement, autism symptoms, behavioral problems, and adaptive abilities as measured by validated, standardized instruments. We predicted that the rate of adverse events would be no more than 10% higher in the everolimus group compared to placebo, and overall severity of side effects would be minimal. We also expected that individuals receiving everolimus would show more improvement, relative to those taking placebo, on the composite neurocognitive index.

Despite education about the risks of excessive sun exposure, teenagers in Australia are sun-seeking, with sunburn common in summer. Conversely, some regular (time-limited) exposure to sunlight (that avoids sunburn) is necessary for vitamin D and healthy bones and other molecules important for immune and metabolic health. New interventions are thus required to better support teenagers to make healthy and balanced decisions about their sun behaviors. This paper describes the development of a prototype online tool—a smartphone app—that aimed to foster safe sun practices in teenagers. We recruited young adolescents (aged 12–13 years, n = 24) as “co-researchers” to provide ongoing input into the nature and design of the online tool. This age group was selected, as it is a critical time when young people transition from primary education, where “SunSmart” behaviors are entrenched in Australian schools, to high school, where risky behaviors emerge. Through a series of interviews and workshops, we codesigned an Apple iOS smartphone app with the co-researchers, leading health promotion professionals, researchers, and app designers. The developed app, Sun Safe, contains educational content relevant to teenagers about safe sun behaviors, complemented by other features requested by co-researchers and stakeholders to help engage young people, including gamified quizzes to test their sun health knowledge, real-time weather data on the UV Index and temperature, a sunscreen application timer, and reminders to check the UV Index. The developed prototype app was rated well by co-researchers, suggesting it is suitable for further feasibility and efficacy testing as an intervention tool to improve knowledge and promote safe sun behaviors by young adolescents.

From noble beginnings as a prospective forage, polyploid Sorghum halepense (‘Johnsongrass’) is both an invasive species and one of the world’s worst agricultural weeds. Formed by S. bicolor x S. propinquum hybridization, we show S. halepense to have S. bicolor-enriched allele composition and striking mutations in 5,957 genes that differentiate it from representatives of its progenitor species and an outgroup. The spread of S. halepense may have been facilitated by introgression from closely-related cultivated sorghum near genetic loci affecting rhizome development, seed size, and levels of lutein, a photochemical protectant and abscisic acid precursor. Rhizomes, subterranean stems that store carbohydrates and spawn clonal propagules, have growth correlated with reproductive rather than other vegetative tissues, and increase survival of both temperate cold seasons and tropical dry seasons. Rhizomes of S. halepense are more extensive than those of its rhizomatous progenitor S. propinquum, with gene expression including many alleles from its non-rhizomatous S. bicolor progenitor. The first surviving polyploid in its lineage in ∼96 million years, its post-Columbian spread across six continents carried rich genetic diversity that in the United States has facilitated transition from agricultural to non-agricultural niches. Projected to spread another 200–600 km northward in the coming century, despite its drawbacks S. halepense may offer novel alleles and traits of value to improvement of sorghum.

Background: Persons with disabilities are generally at greater risk of experiencing violence than their peers without a disability. Within the sphere of disability, individuals with severe communication disabilities are particularly vulnerable and have an increased risk of being a victim of abuse or violence and typically turn to their country’s criminal justice system to seek justice. Unfortunately, victims with disabilities are often denied fair and equal treatment before the court. Transformative equality should be pursued when identifying accommodations in court for persons with communication disabilities, as the aim should be to enable such individuals to participate equally in court, without barriers and discrimination. Objectives: This research aimed to identify court accommodations recommended by legal experts, which could assist individuals with severe communication disabilities in the South African court. Method: A qualitative design was used to conduct a discussion with a panel of legal experts. Results: Using Article 13 (Access to Justice) of the Convention on the Rights of Persons with Disabilities (CRPD) as a human rights framework, four themes were identified: equality, accommodations, participation and training of professionals. Conclusion: Foreign and national law clearly prohibits discrimination against persons with communication disabilities because of their disability and state that they should be given fair and equal access to the court system. For transformative equality to be achieved, certain rules and laws need to be changed to include specific accommodations for persons with communication disabilities so that they may be enabled to participate effectively in court in the criminal justice system.

IntroductionEye diseases and visual impairment more commonly affect elderly adults, thus, the majority of ophthalmic cohort studies have focused on older adults. Cohort studies on the ocular health of younger adults, on the other hand, have been few. The Raine Study is a longitudinal study that has been following a cohort since their birth in 1989–1991. As part of the 20-year follow-up of the Raine Study, participants underwent a comprehensive eye examination. As part of the 27- and 28-year follow-ups, eye assessments are being conducted and the data collected will be compared with those of the 20-year follow-up. This will provide an estimate of population incidence and updated prevalence of ocular conditions such as myopia and keratoconus, as well as longitudinal change in ocular parameters in young Australian adults. Additionally, the data will allow exploration of the environmental, health and genetic factors underlying inter-subject differential long-term ocular changes.Methods and analysisParticipants are being contacted via telephone, email and/or social media and invited to participate in the eye examination. At the 27-year follow-up, participants completed a follow-up eye screening, which assessed visual acuity, autorefraction, ocular biometry and ocular sun exposure. Currently, at the 28-year follow-up, a comprehensive eye examination is being conducted which, in addition to all the eye tests performed at the 27-year follow-up visit, includes tonometry, optical coherence tomography, funduscopy and anterior segment topography, among others. Outcome measures include the incidence of refractive error and pterygium, an updated prevalence of these conditions, and the 8-year change in ocular parameters.Ethics and disseminationThe Raine Study is registered in the Australian New Zealand Clinical Trials Registry. The Gen2 20-year, 27-year and 28-year follow-ups are approved by the Human Research Ethics Committee of the University of Western Australia. Findings resulting from the study will be published in health or medical journals and presented at conferences.Trial registration numberACTRN12617001599369; Active, not recruiting.

IntroductionGreat strides in responding to the HIV epidemic have led to improved access to and uptake of HIV services in Guyana, a lower-middle-income country with a generalized HIV epidemic. Despite efforts to scale up HIV treatment and adopt the test and start strategy, little is known about costs of HIV services across the care cascade.MethodsWe collected cost data from the national laboratory and nine selected treatment facilities in five of the country's ten Regions, and estimated the costs associated with HIV testing and services (HTS) and antiretroviral therapy (ART) from a provider perspective from January 1, 2016 to December 31, 2016. We then used the unit costs to construct four resource allocation scenarios. In the first two scenarios, we calculated how close Guyana would currently be to its 2020 targets if the allocation of funding across programs and regions over 2017-2020 had (a) remained unchanged from latest-reported levels, or (b) been optimally distributed to minimize incidence and deaths. In the next two, we estimated the resources that would have been required to meet the 2020 targets if those resources had been distributed (a) according to latest-reported patterns, or (b) optimally to minimize incidence and deaths.ResultsThe mean cost per test was US$15 and the mean cost per person tested positive was US$796. The mean annual cost per of maintaining established adult and pediatric patients on ART were US$428 and US$410, respectively. The mean annual cost of maintaining virally suppressed patients was US$648. Cost variation across sites may suggest opportunities for improvements in efficiency, or may reflect variation in facility type and patient volume. There may also be scope for improvements in allocative efficiency; we estimated a 28% reduction in the total resources required to meet Guyana's 2020 targets if funds had been optimally distributed to minimize infections and deaths.ConclusionsWe provide the first estimates of costs along the HIV cascade in the Caribbean and assessed efficiencies using novel context-specific data on the costs associated with diagnostic, treatment, and viral suppression. The findings call for better targeting of services, and efficient service delivery models and resource allocation, while scaling up HIV services to maximize investment impact.

Epilepsy is clinically heterogeneous, and neurological or psychiatric comorbidities are frequently observed in patients. It has not been tested whether common risk variants for generalized or focal epilepsy are enriched in people with other disorders or traits related to brain or cognitive function. Here, we perform two brain-focused phenome association studies of polygenic risk scores (PRS) for generalized epilepsy (GE-PRS) or focal epilepsy (FE-PRS) with all binary brain or cognitive function-related traits available for 334,310 European-ancestry individuals of the UK Biobank. Higher GE-PRS were associated with not having a college or university degree (P = 3.00x10-4), five neuroticism-related personality traits (P

Introduction: Cascades, which track the progressive stages of engagement on the path towards a successful outcome, are increasingly being employed to quantitatively assess progress towards targets associated with health and development responses. Maximizing the proportion of people with successful outcomes within a budget-constrained context requires identifying and implementing interventions that are not only effective, but also cost-effective. Methods: We developed a software application called the Cascade Analysis Tool that implements advanced analysis and optimization methods for understanding cascades, combined with the flexibility to enable application across a wide range of areas in health and development. The tool allows users to design the cascade, collate and enter data, and then use the built-in analysis methods in order to answer key policy questions, such as: understanding where the biggest drop-offs along the cascade are; visualizing how the cascade varies by population; investigating the impact of introducing a new intervention or scaling up/down existing interventions; and estimating how available funding should be optimally allocated among available interventions in order to achieve a variety of different objectives selectable by the user (such as optimizing cascade outcomes in target years). The Cascade Analysis Tool is available via a user-friendly web-based application, and comes with a user guide, a library of pre-made examples, and training materials. Discussion: Whilst the Cascade Analysis Tool is still in the early stages of existence, it has already shown promise in preliminary applications, and we believe there is potential for it to help make sense of the increasing quantities of data on cascades.

Although uncommon, pancreas and bile duct injuries can yield devastating outcomes following blunt abdominal trauma. Optimal management of these injuries is widely debated, but historically, surgical repair has been the recommended treatment for high-grade lesions. More recently, there has been interest in non-operative and endoscopic management strategies as less invasive alternatives, especially for pediatric patients. A successful outcome for any of these treatment options depends on several factors including proper diagnosis, stability of the patient, and time from diagnosis to treatment intervention. In this case, we present a 13 year old male who sustained a grade IV pancreatic injury with Grade V common bile duct transection in a remote area of North Dakota. The patient was promptly diagnosed and stabilized with drains. An early decision for endoscopic management was made and successfully carried out several months from the initial injury. The patient has since gone over one year without secondary complications. This case highlights the benefits of a rural trauma system that allowed for cutting edge management for high-grade traumatic injuries. Keywords: Pancreatic injury, Bile duct injury, Non-operative management

Abstract Background Child stunting due to chronic malnutrition is a major problem in low- and middle-income countries due, in part, to inadequate nutrition-related practices and insufficient access to services. Limited budgets for nutritional interventions mean that available resources must be targeted in the most cost-effective manner to have the greatest impact. Quantitative tools can help guide budget allocation decisions. Methods The Optima approach is an established framework to conduct resource allocation optimization analyses. We applied this approach to develop a new tool, ‘Optima Nutrition’, for conducting allocative efficiency analyses that address childhood stunting. At the core of the Optima approach is an epidemiological model for assessing the burden of disease; we use an adapted version of the Lives Saved Tool (LiST). Six nutritional interventions have been included in the first release of the tool: antenatal micronutrient supplementation, balanced energy-protein supplementation, exclusive breastfeeding promotion, promotion of improved infant and young child feeding (IYCF) practices, public provision of complementary foods, and vitamin A supplementation. To demonstrate the use of this tool, we applied it to evaluate the optimal allocation of resources in 7 districts in Bangladesh, using both publicly available data (such as through DHS) and data from a complementary costing study. Results Optima Nutrition can be used to estimate how to target resources to improve nutrition outcomes. Specifically, for the Bangladesh example, despite only limited nutrition-related funding available (an estimated $0.75 per person in need per year), even without any extra resources, better targeting of investments in nutrition programming could increase the cumulative number of children living without stunting by 1.3 million (an extra 5%) by 2030 compared to the current resource allocation. To minimize stunting, priority interventions should include promotion of improved IYCF practices as well as vitamin A supplementation. Once these programs are adequately funded, the public provision of complementary foods should be funded as the next priority. Programmatic efforts should give greatest emphasis to the regions of Dhaka and Chittagong, which have the greatest number of stunted children. Conclusions A resource optimization tool can provide important guidance for targeting nutrition investments to achieve greater impact.

Cooperative learning (CL) is a teaching and learning pedagogy that has been used widely in school but there is limited information on instructors’ perceptions of CL nor observations of how CL is implemented in higher education settings. In this study, we used an interpretative-qualitative approach to investigate the advantages and challenges of embedding CL in instructors’ teaching in Iran and Australia. Data were collected through interviews and observations and thematic analysis method was used to analyse the data. Results showed that despite challenges such as the lack of familiarity with CL and how it can be implemented in university curricula, issues associated with assessment, and time constraints, CL created an interactive, pleasant, and safe environment for deep learning in both countries. The findings showed that there were challenges in Iran such as a tendency to use traditional approaches to teaching, insufficient understanding of how to establish teamwork, and a lack of up-to-date teaching resources. In Australia, changing courses, working with external students, catering for individual differences, and building positive relationships were some of the challenges of implementing CL. We believe that these challenges can be overcome if university instructors are prepared to address them.

Human APOBEC3 enzymes are a family of single-stranded (ss)DNA and RNA cytidine deaminases that act as part of the intrinsic immunity against viruses and retroelements. These enzymes deaminate cytosine to form uracil which can functionally inactivate or cause degradation of viral or retroelement genomes. In addition, APOBEC3s have deamination-independent antiviral activity through protein and nucleic acid interactions. If expression levels are misregulated, some APOBEC3 enzymes can access the human genome leading to deamination and mutagenesis, contributing to cancer initiation and evolution. While APOBEC3 enzymes are known to interact with large ribonucleoprotein complexes, the function and RNA dependence are not entirely understood. To further understand their cellular roles, we determined by affinity purification mass spectrometry (AP-MS) the protein interaction network for the human APOBEC3 enzymes and mapped a diverse set of protein-protein and protein-RNA mediated interactions. Our analysis identified novel RNA-mediated interactions between APOBEC3C, APOBEC3H Haplotype I and II, and APOBEC3G with spliceosome proteins, and APOBEC3G and APOBEC3H Haplotype I with proteins involved in tRNA methylation and ncRNA export from the nucleus. In addition, we identified RNA-independent protein-protein interactions with APOBEC3B, APOBEC3D, and APOBEC3F and the prefoldin family of protein-folding chaperones. Interaction between prefoldin 5 (PFD5) and APOBEC3B disrupted the ability of PFD5 to induce degradation of the oncogene cMyc, implicating the APOBEC3B protein interaction network in cancer. Altogether, the results uncover novel functions and interactions of the APOBEC3 family and suggest they may have fundamental roles in cellular RNA biology, their protein-protein interactions are not redundant, and there are protein-protein interactions with tumor suppressors, suggesting a role in cancer biology. Data are available via ProteomeXchange with the identifier PXD044275.

During HIV infection of CD4+ T cells, ubiquitin pathways are essential to viral replication and host innate immune response; however, the role of specific E3 ubiquitin ligases is not well understood. Proteomics analyses identified 116 single-subunit E3 ubiquitin ligases expressed in activated primary human CD4+ T cells. Using a CRISPR-based arrayed spreading infectivity assay, we systematically knocked out 116 E3s from activated primary CD4+ T cells and infected them with NL4-3 GFP reporter HIV-1. We found 10 E3s significantly positively or negatively affected HIV infection in activated primary CD4+ T cells, including UHRF1 (pro-viral) and TRAF2 (anti-viral). Furthermore, deletion of either TRAF2 or UHRF1 in three JLat models of latency spontaneously increased HIV transcription. To verify this effect, we developed a CRISPR-compatible resting primary human CD4+ T cell model of latency. Using this system, we found that deletion of TRAF2 or UHRF1 initiated latency reactivation and increased virus production from primary human resting CD4+ T cells, suggesting these two E3s represent promising targets for future HIV latency reversal strategies.ImportanceHIV, the virus that causes AIDS, heavily relies on the machinery of human cells to infect and replicate. Our study focuses on the host cell's ubiquitination system which is crucial for numerous cellular processes. Many pathogens, including HIV, exploit this system to enhance their own replication and survival. E3 proteins are part of the ubiquitination pathway that are useful drug targets for host-directed therapies. We interrogated the 116 E3s found in human immune cells known as CD4+ T cells, since these are the target cells infected by HIV. Using CRISPR, a gene-editing tool, we individually removed each of these enzymes and observed the impact on HIV infection in human CD4+ T cells isolated from healthy donors. We discovered that 10 of the E3 enzymes had a significant effect on HIV infection. Two of them, TRAF2 and UHRF1, modulated HIV activity within the cells and triggered an increased release of HIV from previously dormant or "latent" cells in a new primary T cell assay. This finding could guide strategies to perturb hidden HIV reservoirs, a major hurdle to curing HIV. Our study offers insights into HIV-host interactions, identifies new factors that influence HIV infection in immune cells, and introduces a novel methodology for studying HIV infection and latency in human immune cells.

PurposeChronic inflammation is integral to myeloproliferative neoplasm (MPN) pathogenesis. JAK inhibitors reduce cytokine levels, but not without significant side effects. Nutrition is a low-risk approach to reduce inflammation and ameliorate symptoms in MPN. We performed a randomized, parallel-arm study to determine the feasibility of an education-focused Mediterranean diet intervention among patients with MPN.Experimental designWe randomly assigned patients with MPN to either a Mediterranean diet or standard U.S. Dietary Guidelines for Americans (USDA). Groups received equal but separate education with registered dietician counseling and written dietary resources. Patients were prospectively followed for feasibility, adherence, and symptom burden assessments. Biological samples were collected at four timepoints during the 15-week study to explore changes in inflammatory biomarkers and gut microbiome.ResultsThe Mediterranean diet was as easy to follow for patients with MPN as the standard USDA diet. Approximately 80% of the patients in the Mediterranean diet group achieved a Mediterranean Diet Adherence Score of ≥8 throughout the entire active intervention period, whereas less than 50% of the USDA group achieved a score of ≥8 at any timepoint. Improvement in symptom burden was observed in both diet groups. No significant changes were observed in inflammatory cytokines. The diversity and composition of the gut microbiome remained stable throughout the duration of the intervention.ConclusionsWith dietician counseling and written education, patients with MPN can adhere to a Mediterranean eating pattern. Diet interventions may be further developed as a component of MPN care, and potentially incorporated into the management of other hematologic conditions.SignificanceDiet is a central tenant of management of chronic conditions characterized by subclinical inflammation, such as cardiovascular disease, but has not entered the treatment algorithm for clonal hematologic disorders. Here, we establish that a Mediterranean diet intervention is feasible in the MPN patient population and can improve symptom burden. These findings warrant large dietary interventions in patients with hematologic disorders to test the impact of diet on clinical outcomes.

Abstract Background The high burden of malaria and limited funding means there is a necessity to maximize the allocative efficiency of malaria control programmes. Quantitative tools are urgently needed to guide budget allocation decisions. Methods A geospatial epidemic model was coupled with costing data and an optimization algorithm to estimate the optimal allocation of budgeted and projected funds across all malaria intervention approaches. Interventions included long-lasting insecticide-treated nets (LLINs), indoor residual spraying (IRS), intermittent presumptive treatment during pregnancy (IPTp), seasonal mass chemoprevention in children (SMC), larval source management (LSM), mass drug administration (MDA), and behavioural change communication (BCC). The model was applied to six geopolitical regions of Nigeria in isolation and also the nation as a whole to minimize incidence and malaria-attributable mortality. Results Allocative efficiency gains could avert approximately 84,000 deaths or 15.7 million cases of malaria in Nigeria over 5 years. With an additional US$300 million available, approximately 134,000 deaths or 37.3 million cases of malaria could be prevented over 5 years. Priority funding should go to LLINs, IPTp and BCC programmes, and SMC should be expanded in seasonal areas. To minimize mortality, treatment expansion is critical and prioritized over some LLIN funding, while to minimize incidence, LLIN funding remained a priority. For areas with lower rainfall, LSM is prioritized over IRS but MDA is not recommended unless all other programmes are established. Conclusions Substantial reductions in malaria morbidity and mortality can be made by optimal targeting of investments to the right malaria interventions in the right areas.

Central venous access is a common procedure that is performed for a variety of reasons. However, occasionally these lines can be misplaced at an improper anatomic location despite fluoroscopic guidance. Here we present a pediatric case in which a central venous port appeared correctly located on anterior-posterior (AP) fluoroscopic view. However, it was later discovered on lateral views that the catheter was placed in the azygos vein. The catheter eroded through the azygos vein and into the pleural space. This article highlights the importance of proper technique when placing central lines and discusses additional techniques and avenues of research in order to prevent this complication in the future. Keywords: Central venous access, Complications, Azygos vein

Abstract Background Photodamage is partially mitigated by darker skin pigmentation, but immune suppression, photoaging and cataracts occur among individuals with all skin types. Methods To assess practices and acceptability to Black African mothers of sun protection equipment for their children living in a rural area, participants were recruited at the time of their child’s 18-month vaccinations. Mothers completed a baseline questionnaire on usual sun behaviours and sun protection practices. They were then provided with sun protection equipment and advice. A follow-up questionnaire was administered two weeks later. Results Mothers reported that during the week prior to the baseline questionnaire, children spent on average less than 1 hour of time outdoors (most often spent in the shade). Most mothers (97%) liked the sun protection equipment. However, many (78 of 86) reported that their child did not like any of the sun protection equipment and two-thirds stated that the sun protection equipment was not easy to use. Conclusions Among Black Africans in rural northern South Africa, we found a mismatch between parental preferences and child acceptance for using sun protection when outdoors. A better understanding of the health risks of incidental excess sun exposure and potential benefits of sun protection is required among Black Africans.

Professional antigen presenting cells (APC) are the major activator of T cells that then hone to sites of inflammation. Using islet cell grafts, here the authors show that parenchymal cells can present antigen to activate CD8+T cells at inflammatory sites, coining this a ‘mezzanine response’ distinct from primary and secondary responses associated with professional APCs.

Abstract High-force eccentric exercise results in sustained increases in cytoplasmic Ca2+ levels ([Ca2+]cyto), which can cause damage to the muscle. Here we report that a heavy-load strength training bout greatly alters the structure of the membrane network inside the fibres, the tubular (t-) system, causing the loss of its predominantly transverse organization and an increase in vacuolation of its longitudinal tubules across adjacent sarcomeres. The transverse tubules and vacuoles displayed distinct Ca2+-handling properties. Both t-system components could take up Ca2+ from the cytoplasm but only transverse tubules supported store-operated Ca2+ entry. The retention of significant amounts of Ca2+ within vacuoles provides an effective mechanism to reduce the total content of Ca2+ within the fibre cytoplasm. We propose this ability can reduce or limit resistance exercise-induced, Ca2+-dependent damage to the fibre by the reduction of [Ca2+]cyto to help maintain fibre viability during the period associated with delayed onset muscle soreness.

Abstract Background Vaccination is a mainstay of preventive healthcare, reducing the incidence of serious childhood infections. Ecological studies have demonstrated an inverse association between markers of high ambient ultraviolet (UV) radiation exposure (e.g., sunny season, low latitude of residence) and reduction in the vaccination-associated immune response. Higher sun exposure on the day prior to and spanning the day of vaccination has been associated with a reduced antigen-specific immune response independent of skin pigmentation. The South African Department of Health’s Expanded Programme on Immunisation provides free vaccinations in government primary health care clinics. In some areas, these clinics may have only a small waiting room and patients wait outside in full sun conditions. In rural areas, patients may walk several kilometres to and from the clinic. We hypothesised that providing sun protection advice and equipment to mothers of children (from 18 months) who were waiting to be vaccinated would result in a more robust immune response for those vaccinated. Methods We conducted an intervention study among 100 children receiving the booster measles vaccination. We randomised clinics to receive (or not) sun protection advice and equipment. At each clinic we recorded basic demographic data on the child and mother/carer participants, their sun exposure patterns, and the acceptability and uptake of the provided sun protection. At 3–4 weeks post-vaccination, we measured measles IgG levels in all children. Discussion This is the first intervention study to assess the effect of sun protection measures on vaccine effectiveness in a rural, real-world setting. The novel design and rural setting of the study can contribute much needed evidence to better understand sun exposure and protection, as well as factors determining vaccine effectiveness in rural Africa, and inform the design of immunisation programmes. (TRN PACTCR201611001881114, 24 November 2016, retrospective registration)

Pulmonary histoplasmosis is caused by infection with Histoplasma capsulatum, resulting in a variety of clinical manifestations. We describe a case of an asymptomatic mediastinal mass and calcified pulmonary nodules discovered in immunocompetent child from the Southeastern United States. In the setting of inconclusive noninvasive diagnostic tests and the inability to completely exclude malignancy, the patient was taken to the operating room for excisional biopsy of the mass and right upper lobe lung nodules. A diagnosis of histoplasmosis with mediastinal granulomas was established. The patient was subsequently treated with itraconazole. This article underscores the importance of including endemic mycoses in the differential for mediastinal mass and discusses the utility of surgical intervention for the diagnosis and treatment of histoplasmosis. Keywords: Histoplasmosis, Mediastinal mass, Cryptococcus

Background: After several years of storing a large number of historical medical books that had been weeded from the general collection, the University of New Mexico Health Sciences Library and Informatics Center developed a set of evaluation criteria to determine whether the material should be kept and included in the library catalog or discarded. The purpose of this article is to share lessons learned in evaluating and processing a historical medical book collection. The authors share how we determined review criteria as well as cataloging and processing procedures. Case Presentation: Best practices for evaluating, cataloging, and processing historical library material were determined through a literature search and then reviewed and adapted for application to this project. Eight hundred sixty-two titles were selected to add to the catalog and were added to a shelving location in our offsite storage facility. Conclusions: These materials are now discoverable in the library’s catalog for library users who are interested in historical research, and the materials have been processed for easy retrieval as well as preservation purposes.

The red-eared slider turtle (Trachemys scripta elegans; RES) is often considered one of the world’s most invasive species. Results from laboratory and mesocosm experiments suggest that introduced RES outcompete native turtles for key ecological resources, but such experiments can overestimate the strength of competition. We report on the first field experiment with a wild turtle community, involving introduced RES and a declining native species of conservation concern, the western pond turtle (Emys marmorata; WPT). Using a before/after experimental design, we show that after removing most of an introduced RES population, the remaining RES dramatically shifted their spatial basking distribution in a manner consistent with strong intraspecific competition. WPT also altered their spatial basking distribution after the RES removal, but in ways inconsistent with strong interspecific competition. However, we documented reduced levels of WPT basking post-removal, which may reflect a behavioral shift attributable to the lower density of the turtle community. WPT body condition also increased after we removed RES, consistent with either indirect or direct competition between WPT and RES and providing the first evidence that RES can compete with a native turtle in the wild. We conclude that the negative impacts on WPT basking by RES in natural contexts are more limited than suggested by experiments with captive turtles, although wild WPT do appear to compete for food with introduced RES. Our results highlight the importance of manipulative field experiments when studying biological invasions, and the potential value of RES removal as a management strategy for WPT.

Oncology treatment has been revolutionized by the introduction of immune checkpoint inhibitor drugs, which enable 20–40% of patients to generate anti-tumor immune responses. Combination treatment approaches with chemotherapeutic drugs may enable responses in the remaining patient cohorts. In this regard, a handful of drugs are promising due to their ability to induce immunogenic cell death in target cells. However, these agents are systemically delivered and indiscriminately cytotoxic to proliferating cells. By contrast, antibody-drug conjugates can selectively deliver a cytotoxic payload to a tumor, sparing most healthy cells. The ability of antibody-drug conjugates to induce immunogenic cell death in target cells has not yet been determined, although preclinical in vivo studies suggest this possibility. Here, we describe for the first time production of the in vitro hallmarks of immunogenic cell death – ecto-calreticulin and secreted ATP and HMGB1 protein – by cells in response to treatment with antibody-drug conjugates bearing a maytansine payload.