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Kids SIP"smart"ER is a 6-month behavioral and health literacy intervention effective at reducing sugar-sweetened beverage (SSB) intake among middle school students and their caregivers in the rural Appalachian region. This exploratory mixed methods study utilized a convergent parallel design to assess participant acceptability of a school-based curriculum for students and a text messaging program for caregivers. Acceptability was assessed using surveys (873 students and 453 caregivers), five focus groups (34 students) and telephone interviews (22 caregivers). Quantitative data were analyzed descriptively, and qualitative data were content coded. On a 5-point scale, average quantitative survey acceptability ratings ranged from 2.7 to 3.3 among three student-rated questions and 4.1 to 4.2 among four caregiver-rated questions. Qualitative focus group findings suggested that students preferred curricular activities that were hands-on and involved social interaction, while caregiver interview results showed high acceptability of the text messaging program's design, including usability, content messages and personalization. Students and caregivers reported similar program benefits: increased knowledge of SSBs and health risks, increased awareness of SSB behaviors and support to make beverage behavior changes. Results from this study can be used to understand Kids SIP"smart"ER's effectiveness data, communicate the intervention's acceptability with stakeholders and plan for future implementation studies.

Background: Adolescents with overweight or obesity are at greater risk of having physical and psychosocial consequences. With increased disparities and inadequate literature on prevalence of adolescent weight status in rural Appalachia, there is potential for further complications. Unfortunately, adolescent obesity treatment options are often limited, especially in medically underserved regions. Methods: This cross-sectional study of adolescents at eight rural Appalachian schools examined weight status among and associations between body mass index percentile (BMIp) categories and health-related perceptions and weight-control intentions. Previously validated instruments were utilized. Analyses included independent samples t-tests, ANOVA tests, and chi-squared tests. Results: Of 814 adolescents (ages 11-13; 55.0% girls), BMIp revealed 20.8% overweight, 22.7% obese, and 10.6% severely obese. Adolescents with higher BMIp categories reported poorer self-rated health, inaccurate weight perceptions, and greater weight loss intentions (all p < 0.05). Conclusions: Findings, including high prevalence of adolescents with overweight and obesity, emphasize the need for more obesity prevention and treatment options. Schools may be an ideal setting to reach at-risk adolescents and provide obesity prevention and treatment options, especially in medically underserved regions such as rural Appalachia. Opportunities and challenges to apply findings, including school-based obesity programs, are discussed.

Public health campaigns have the potential to correct vaping misperceptions. However, campaigns highlighting vaping harms to youth may increase misperceptions that vaping is equally/more harmful than smoking. Vaping campaigns have been implemented in the United States and Canada since 2018 and in England since 2017 but with differing focus: youth vaping prevention (United States/Canada) and smoking cessation (England). We therefore examined country differences and trends in noticing vaping campaigns among youth and, using 2022 data only, perceived valence of campaigns and associations with harm perceptions. Seven repeated cross-sectional surveys of 16-19 year-olds in United States, Canada and England (2018-2022, n = 92 339). Over half of youth reported noticing vaping campaigns, and noticing increased from August 2018 to February 2020 (United States: 55.2% to 74.6%, AOR = 1.21, 95% CI = 1.18-1.24; Canada: 52.6% to 64.5%, AOR = 1.13, 1.11-1.16; England: 48.0% to 53.0%, AOR = 1.05, 1.02-1.08) before decreasing (Canada) or plateauing (England/United States) to August 2022. Increases were most pronounced in the United States, then Canada. Noticing was most common on websites/social media, school and television/radio. In 2022 only, most campaigns were perceived to negatively portray vaping and this was associated with accurately perceiving vaping as less harmful than smoking among youth who exclusively vaped (AOR = 1.46, 1.09-1.97). Consistent with implementation of youth vaping prevention campaigns in the United States and Canada, most youth reported noticing vaping campaigns/messages, and most were perceived to negatively portray vaping.

Abstract Background Prevalence of youth nicotine vaping has increased, heightening concerns around negative health effects. This study aimed to compare self-reported respiratory symptoms among youth by vaping behaviours. Methods Participants (n = 39,214) aged 16–19 from the 2020 and 2021 International Tobacco Control Policy Evaluation Project (ITC) Youth Tobacco and Vaping Surveys (Canada, England, US). Weighted multivariable logistic regression assessed associations between reporting any of five respiratory symptoms in the past week (shortness of breath, wheezing, chest pain, phlegm, cough) and: past 30-day smoking and/or vaping; lifetime/current vaping. Among past-30-day vapers (n = 4644), we assessed associations between symptoms and vaping frequency, use of nicotine salts, usual flavour and device type(s). Results Overall, 27.8% reported experiencing any of the five respiratory symptoms. Compared with youth who had only vaped, those who had only smoked had similar odds of symptoms [adjusted odds ratio, OR (95% confidence interval, CI): 0.97 (0.85–1.10)], those who both smoked and vaped had higher odds [1.26 (1.12–1.42)], and those who had done neither, lower odds [0.67 (0.61–0.72)]. Compared with those who had never vaped, past use, experimentation and current regular or occasional use were all associated with higher odds. Reporting usually using nicotine salts was associated with higher odds of symptoms [1.43 (1.22–1.68)] than non-salt but was often uncertain. Compared with tobacco flavour (including with menthol), menthol/mint and sweets flavours were associated with similar odds; fruit [1.44 (1.07–1.93)], multiple [1.76 (1.30–2.39)] and ‘other’ [2.14 (1.45–3.16)] flavours with higher odds. All device types were associated with similar odds. Conclusions Among youth, vaping was associated with increased reporting of past-week respiratory symptoms. Among those who vaped, some flavour types and potentially nicotine salts were associated with respiratory symptoms.

We demonstrate resonant excitation of a plasma wave by a train of short laser pulses guided in a preformed plasma channel, for parameters relevant to a plasma-modulated plasma accelerator (P-MoPA). We show experimentally that a train of N≈10 short pulses, of total energy ∼1J, can be guided through 110mm long plasma channels with on-axis densities in the range 10^{17}–10^{18}cm^{−3}. The spectrum of the transmitted train is found to be strongly red shifted when the plasma period is tuned to the intratrain pulse spacing. Numerical simulations are found to be in excellent agreement with the measurements and indicate that the resonantly excited plasma waves have an amplitude in the range 3–10GVm^{−1}, corresponding to an accelerator stage energy gain of order 1GeV.

Abstract Plasma circulating tumour DNA (ctDNA) has been suggested to be a viable biomarker of response to treatment in patients with high grade serous ovarian carcinoma (HGSOC). TP53 mutations are present in more than 90% of HGSOCs but somatic variants are distributed across all exonic regions of the gene, requiring next generation sequencing (NGS) technologies for mutational analysis. In this study, we compared the suitability of the Accel (Swift) and Oncomine (ThermoFisher) panels for identification of TP53 mutations in ctDNA of HGSOC patients (N = 10). Only 6 patients (60%) were found to have TP53 mutations using the ACCEL panel but the addition of molecular tags in the Oncomine panel improved ctDNA detection with at least one mutation detected in all cases (100%). Orthogonal validation of the 14 somatic variants found by Oncomine, using droplet digital PCR, confirmed 79% (11/14) of the identified mutations. Overall, the Oncomine panel with unique molecular identifiers (UMI) appears more useful for ctDNA analysis in HGSOC.

Objectives: This paper describes trends in youth e-cigarette (EC) and tobacco cigarette (TC) purchasing behaviors in Canada, England, and the United States (US) in relationship to changing minimum legal age (MLA) laws.Methods: Data are from eight cross-sectional online surveys among national samples of 16- to 19-year-olds in Canada, England, and the US conducted from 2017 to 2022 (N = 104,467). Average wave percentage change in EC and TC purchasing prevalence and purchase locations were estimated using Joinpoint regressions.Results: EC purchasing increased between 2017 and 2022, although the pattern of change differed by country. EC purchasing plateaued in 2019 for the US and in 2020 for Canada, while increasing through 2022 for England. TC purchasing declined sharply in the US, with purchasing from traditional retail locations declining, while purchasing from social sources increased. Vape shops were the most common location for EC purchasing, although declining in England and the US.Conclusion: Trends in EC and TC purchasing trends in the US are consistent with the expected impact of the federal MLA law increasing the legal age to 21 years in December 2019.

Several nicotine vaping product (NVP) device types are available to consumers, and many people who smoke report vaping to help them quit. This study included data from the Wave 3 (2020) ITC Smoking and Vaping Survey in the US, Canada, and England and included 2324 adults who were smoking cigarettes and vaping at least weekly. Device types currently used most often (disposables, cartridges/pods, or tank systems) were assessed using weighted descriptive statistics. Multivariable regression analyses were used to compare differences between respondents who reported vaping to quit smoking (‘yes’ vs. ‘no/don’t know’) by device type, overall and by country. Overall, 71.3% of respondents reported vaping to help them quit smoking, with no country differences (p = 0.12). Those using tanks (78.7%, p

Abstract This study investigated morphological characteristics of the soleus muscle in cerebral palsy (CP) and typically developing (TD) cohorts using a statistical shape model and differentiated dominant features between the two cohorts. We generated shape models of CP and TD cohorts to characterize dominant features within each. We then generated a combined shape model of both CP and TD to assess deviations of the cohorts’ soleuses from a common mean shape, and statistically analysed differences between the cohorts. The shape models revealed similar principal components (PCs) with different variance between groups. The CP shape model yielded a distinct feature (superior–inferior shift of the broad central region) accounting for 8.1% of the model’s cumulative variance. The combined shape model presented two PCs where differences arose between CP and TD cohorts: size and aspect ratio of length–width–thickness. The distinct appearance characteristic in the CP model—described above—may implicate impaired muscle function in children with CP. Overall, children with CP had smaller muscles that also tended to be long, thin, and narrow. Shape modelling captures dominant morphological features of structures, which was used here to quantitatively describe CP muscles and further probe our understanding of the disease’s impact on the muscular system.

Summary: Background: Communication is the foundation of a strong doctor–patient relationship. Holistic care of the patient involves good communication and empathy. There are various tools and interventions aimed at increasing the Surgeon's performance, but these have the drawback of heavy cost and time commitments. In contrast, patient focused interventions are often simple and cheap. In surgery this is an evolving field, and little is known about the impact these interventions have on clinical encounters. The aim of this review is to determine how patient focussed interventions impact communication in the Surgical Outpatient Consultation. Methods: In this systematic review and meta-analysis, two reviewers independently searched MEDLINE (incl. PubMed), EMBASE, EMCARE, CINAHL, and the Cochrane Library for the period starting 01 February 1990 to 01 February 2022. Filtration and screening was performed in accordance with PRISMA guidelines. Conflicts were resolved by discussion. Risk of Bias was assessed using the RoB 2 tool. Meta-analyses were conducted by an independent statistician using Stata Statistical Software. This systematic review was prospectively registered with PROSPERO (ID CRD42022311112). Findings: After screening, 38 papers were included in the final analysis. These involved 6392 patients consisting of 32 randomised controlled trials (RCT), one crossover RCT, three non-randomised experimental studies, and three cohort studies. All articles were published between 1999 and 2022. Four types of intervention were identified: Patient Decision Aids, Educational Materials, Question Prompt Lists and Patient Reported Outcome Measures. There was much heterogeneity in the reported results but ultimately four recurring domains for assessing quality of communication were identified: Patient knowledge; decisional conflict; satisfaction; and anxiety. Meta-analyses showed that patient focussed interventions increased patient knowledge and reduced decisional conflict. Meta-regression demonstrated significant knowledge increases in females compared with males. Results regarding satisfaction and anxiety were not statistically significant. Interpretation: Our study suggested that patient focused interventions demonstrate promising results for increasing patient engagement and improving communication. Further multicentre randomised controlled trials with consistent validated endpoints should be conducted to evaluate this evolving field. Funding: There was no funding source for this study.

ABSTRACT Perennial grass energy crop production is necessary for the successful and sustainable expansion of bioenergy in North America. Numerous environmental advantages are associated with perennial grass cropping systems, including their potential to promote soil carbon accrual. Despite growing research interest in the abiotic and biotic factors driving soil carbon cycling within perennial grass cropping systems, soil fauna remain a critical yet largely unexplored component of these ecosystems. By regulating microbial activity and organic matter decomposition dynamics, soil fauna influence soil carbon stability with potentially significant implications for soil carbon accrual. We begin by reviewing the diverse, predominantly indirect effects of soil fauna on soil carbon dynamics in the context of perennial grass cropping systems. Since the impacts of perennial grass energy crop production on soil fauna will mediate their potential contributions to soil carbon accrual, we then discuss how perennial grass energy crop traits, diversity, and management influence soil fauna community structure and activity. We assert that continued research into the interactions of soil fauna, microbes, and organic matter will be important for advancing our understanding of soil carbon dynamics in perennial grass cropping systems. Furthermore, explicit consideration of soil faunal effects on soil carbon can improve our ability to predict changes in soil carbon following perennial grass cropping system establishment. We conclude by addressing the major knowledge gaps that should be prioritized to better understand and model the complex connections between perennial grass bioenergy systems, soil fauna, and carbon accrual.

Abstract We conducted a systematic review on the impacts of natural causes of variation or changes in flow magnitude (resulting from climatic variability and broad‐scale drivers such as climate‐induced change) on fish abundance and biomass in temperate regions. Following our systematic review protocol (Birnie‐Gauvin et al., 2021), we examined commercially published and grey literature originally identified during a recent systematic map process (Rytwinski et al., 2020) and a systematic search update. Articles were screened using an a priori eligibility criteria, with consistency checks performed at the title and abstract, and full text screening stages. All eligible articles were assessed for study validity. A narrative synthesis included all available evidence (300 studies from 219 articles), and meta‐analyses (1863 datasets from 193 studies) were conducted where appropriate. Most studies were conducted in the United States (65%) on genera in the Salmonidae and Leuciscidae families (29% and 28%, respectively), and mainly investigated variation in flow magnitude, followed by droughts and floods. We found that fish abundance and biomass responses to changes in natural flow magnitude were mainly negative, but analyses do not support clear generalizable signals across all contexts (e.g. types of changes in flow magnitude, taxa, locations). When exploring reasons for heterogeneity in effect sizes, we found a detectable effect of intervention type on average fish abundance within the first year of the natural change in flow magnitude, with floods and droughts associated with overall negative responses. However, these patterns were more variable when considering between‐year variation or specific taxonomic responses. Our results suggest that while immediate responses were more apparent and relatively consistent within specific types of natural events, fish populations may recover after such events (i.e. ≥2 years post‐natural event); however, most studies were short in duration (

Skeletal muscle regulation is responsible for voluntary muscular movement in vertebrates. The genes of two essential proteins, teneurins and latrophilins (LPHN), evolving in ancestors of multicellular animals form a ligand-receptor pair, and are now shown to be required for skeletal muscle function. Teneurins possess a bioactive peptide, termed the teneurin C-terminal associated peptide (TCAP) that interacts with the LPHNs to regulate skeletal muscle contractility strength and fatigue by an insulin-independent glucose importation mechanism in rats. CRISPR-based knockouts and siRNA-associated knockdowns of LPHN-1 and-3 in the C2C12 mouse skeletal cell line shows that TCAP stimulates an LPHN-dependent cytosolic Ca2+ signal transduction cascade to increase energy metabolism and enhance skeletal muscle function via increases in type-1 oxidative fiber formation and reduce the fatigue response. Thus, the teneurin/TCAP-LPHN system is presented as a novel mechanism that regulates the energy requirements and performance of skeletal muscle.

Duchenne muscular dystrophy (DMD) is a progressive, X-linked childhood neuromuscular disorder that results from loss-of-function mutations in the DYSTROPHIN gene. DMD patients exhibit muscle necrosis, cardiomyopathy, respiratory failure, and loss of ambulation. One of the major driving forces of DMD disease pathology is chronic inflammation. The current DMD standard of care is corticosteroids; however, there are serious side effects with long-term use, thus identifying novel anti-inflammatory and anti-fibrotic treatments for DMD is of high priority. We investigated the next-generation SINE compound, KPT−8602 (eltanexor) as an oral therapeutic to alleviate dystrophic symptoms. We performed pre-clinical evaluation of the effects of KPT−8602 in DMD zebrafish (sapje) and mouse (D2-mdx) models. KPT−8602 improved dystrophic skeletal muscle pathologies, muscle architecture and integrity, and overall outcomes in both animal models. KPT−8602 treatment ameliorated DMD pathology in D2-mdx mice, with increased locomotor behavior and improved muscle histology. KPT−8602 altered the immunological profile of the dystrophic mice, and reduced circulating osteopontin serum levels. These findings demonstrate KPT−8602 as an effective therapeutic in DMD through by promotion of an anti-inflammatory environment and overall improvement of DMD pathological outcomes.

At the Stollery Children’s Chronic Pain Clinic, new referrals are assessed by an interdisciplinary team. The final part of the intake assessment typically involves an explanation and compassionate validation of the etiology of chronic pain and an invitation to the youth to attend the group outpatient Cognitive Behavioural Therapy (CBT) program, called Pain 101, or to individual outpatient CBT. It was hypothesized that a brief physician-delivered CBT (brief-CBT) intervention at first point of contact improves subsequent pain acceptance. Using a randomized double blinded methodology, 26 participants received a standard intake assessment and 26 the standard assessment plus the brief-CBT intervention. Measures were taken at three points: pre and post-intake assessment and after Pain 101 or individual CBT (or day 30 post-assessment for those attending neither). The primary outcome measure was the Chronic Pain Acceptance Questionnaire—Adolescent version (CPAQ-A). Comparing pre and post-intake measures, there was a significant (p = 0.002) increase in the CPAQ-A scores—four-fold more in the brief-CBT intervention group (p = 0.045). Anxiety (RCADS-T Score) was significantly reduced post-intake and significantly more reduced in the intervention group compared to the control group (p = 0.024). CPAQ-A scores were significantly increased (p < 0.001) (N = 28) and anxiety (RCADs-T) was significantly reduced by the end of Pain 101 (p < 0.003) (N = 29) as was fear of pain as measured by the Tampa Scale for Kinesiophobia (p = 0.021). A physician-delivered brief-CBT intervention significantly and meaningfully increased CPAQ-A scores and reduced anxiety in youth with chronic pain. Furthermore, CBT through Pain 101 is effective at increasing acceptance, as well as reducing anxiety and fear of movement.

Teneurin C-terminal associated peptides (TCAP), bioactive peptides located on the C-terminal end of teneurin proteins, have been shown to regulate stress axis functions due to the high conservation between TCAP and corticotropin releasing factor (CRF). Additionally, recent work demonstrated that TCAP can increase metabolism in rats via glucose metabolism. These metabolic actions are not well described in other organisms, including teleosts. Here we investigated the expression of a tcap isoform, tcap-3, and the potential role of TCAP-3 as a regulator of metabolism across zebrafish life-stages. Using pcr-based analyses, tcap-3 appears to be independently transcribed, in relation to teneurin-3, in muscle tissue of adult zebrafish. Resazurin, respirometry chambers, and mitochondrial metabolism analyses were used to study the metabolic effects of synthetic rainbow trout TCAP-3 (rtTCAP-3) in larval and adult zebrafish. Overall, metabolic activity was enhanced by 48 h of rtTCAP-3 treatment in larvae (bath immersion) and adults (intraperitoneal injections). This metabolic activity increase was due to mitochondrial uncoupling, as mitochondrial respiration increase by rtTCAP-3 was due to proton leak. Additionally, rtTCAP-3 protected larval fish from reduced metabolic activity induced by low temperatures. Subsequently, rtTCAP-3 increased metabolic output in adult zebrafish subjected to accelerated swimming speeds, demonstrating the potent role of rtTCAP-3 in zebrafish metabolism regulation during metabolic challenges. Collectively, these results demonstrate the conserved roles for rtTCAP-3 as a metabolic activator in zebrafish.

The economic valuation of ecosystem services in part reflects the desire to use conventional economic tools (markets and economic instruments) to conserve ecosystem services. However, for regulating and supporting ecosystem services that depend on ecosystem structure and function, estimation of economic value requires estimates of the current level of underlying ecological functions first. This primary step is in principle, the job of environmental scientists, not economists. Here, we provide a coarse-level quantitative assessment of the relationship between the research effort expended by environmental scientists (on the biophysical values) and economists (on the monetary values) on 15 different regulating and supporting services in 32 ecosystem types using peer-reviewed article hits retrieved from bibliographic databases as a measure of research effort. We find a positive, moderately strong (r = 0.69) correlation between research efforts in the two domains, a result that, while encouraging, is likely to reflect serendipity rather than the deliberate design of integrated environmental science-economics research programs. Our results suggest that compared to environmental science research effort economic valuation is devoted to a smaller, less diverse set of ecosystem services but a broader, more diverse, set of ecosystem types. The two domains differed more with respect to the ecosystem services that are the major focus of research effort than they did with respect to the ecosystem types of principal research interest. For example, carbon sequestration, erosion regulation, and nutrient cycling receive more relative research effort in the environmental sciences; air quality regulation in economic valuations. For both domains, cultivated areas, wetlands, and urban/semi-urban ecosystem types received relatively large research effort, while arctic and mountain tundra, cave and subterranean, cryosphere, intertidal/littoral zone, and kelp forest ecosystem types received negligible research effort. We suggest ways and means by which the field of sustainability science may be improved by the design and implementation of a searchable database of environmental science and economic valuation literature as well as a global ecosystem service research network and repository that explicitly links research on the estimation and prediction of biophysical ecosystem functions with that of the social sciences and other knowledge systems. These suggestions would, at least in principle, facilitate a more efficient research agenda between economists and environmental scientists and aid management, regulatory and judicial decision-makers.

Objectives There is a gap in research exploring perceptions of runners and healthcare professionals (HCPs) about running footwear and injury risk. The objectives of this study were: (1) to document factors considered by runners when selecting footwear; (2) to compare perceptions on footwear and injury risk in runners and HCPs; and (3) to evaluate the perceived usefulness of an online educational module.Methods Using an online survey, we collected information on demographics and perceptions about footwear and injury risk. Runners reported their footwear selection strategy, and HCPs their typical recommendations. An evidence-based educational module was presented, and participants rated its usefulness.Results The survey was completed by 2442 participants, of which 1035 completed the optional postmodule questions. Runners reported relying mostly on comfort and advice from retailers when selecting shoes. Perceptions regarding the effects of specific footwear types (minimalist, maximalist), characteristics (softness, drop) and selection strategy (foot type, transition) on biomechanics and injury risk were different between HCPs and runners. Overall, runners perceived footwear as more important to prevent injury than did HCPs (7.6/10, 99% CI 7.4 to 7.7 vs 6.2/10, 99% CI 6.0 to 6.5; p

Integrated or interdisciplinary curriculum (IC) is an effective and relevant way to teach the 21st century competencies and to apply the transdisciplinary skills necessary for solving complex global problems. We review the underpinnings of both traditional and progressive education and past periods of implementation of IC in order to understand its history. Multiple definitions of IC are identified on a continuum. Reasons to dismiss the continuum are also offered. Two periods when IC was implemented in a consistent way in the United States are explored: the progressive era from 1919 to 1955, and the late 1980s and early 1990s. Similarities in each era are identified such as progressive principles of teaching and learning. Differences are also considered in basic assumptions held by curriculum developers of the day with the 1980s and 1990s lacking the 1930s deep social purpose of teaching for a democratic society. The socio-political context is visited to understand the beginnings and endings of these eras. The current educational context is then viewed from a global context. We see a landscape in which accountability and disciplines are counterbalanced by a global redefinition of what’s worth knowing and a shift toward interdisciplinary competencies/skills/capabilities, well-being and teaching the whole child. Indeed, this is happening in places around the planet such as Finland. The ideas are reminiscent of the 1930s progressive movement—a time of experimentation when student interests and needs more than disciplinary content shaped an IC. We propose that the current global conversation can offer conceptual cohesion to encourage and support the implementation of IC and can act as a proxy for the Progressive Education Association that guided practitioners from 1919 to 1955.

Background: The development of biomarkers predictive of response to immune checkpoint inhibitor (ICI) therapies in advanced melanoma is an area of great interest in oncology. Our study evaluated the potential role of serum vascular endothelial growth factor (VEGF) as a predictive biomarker of clinical benefit and response to treatment with ICIs.Methods: Pre-treatment peripheral blood samples were obtained from advanced melanoma patients undergoing ICI therapy as monotherapy or in combination at two tertiary care hospitals in Western Australia. Serum VEGF levels were correlated with response to therapy and survival outcomes.Results: Serum VEGF samples were collected from a total of 130 patients treated with ICI therapy (pembrolizumab 73, ipilimumab 15, and ipilimumab/nivolumab combination 42). Median serum VEGF level was significantly higher in the non-responders (82.15 pg/mL) vs. responders (60.40 pg/mL) in the ipilimumab monotherapy cohort (P < 0.0352). However, no difference was seen in VEGF levels between non-responders and responders in pembrolizumab and ipilimumab/nivolumab treated patients.Conclusions: The results of our study confirm previous observations that that high pre-treatment serum VEGF levels in advanced melanoma patients may predict poor response to ipilimumab. However, serum VEGF is not predictive of outcome in patients treated with anti-PD-1 agents alone or in combination with ipilimumab.

Circulating tumor DNA (ctDNA) may serve as a surrogate to tissue biopsy for noninvasive identification of mutations across multiple genetic loci and for disease monitoring in melanoma. In this study, we compared the mutation profiles of tumor biopsies and plasma ctDNA from metastatic melanoma patients using custom sequencing panels targeting 30 melanoma‐associated genes. Somatic mutations were identified in 20 of 24 melanoma biopsies, and 16 of 20 (70%) matched‐patient plasmas had detectable ctDNA. In a subgroup of seven patients for whom matching tumor tissue and plasma were sequenced, 80% of the mutations found in tumor tissue were also detected in ctDNA. However, TERT promoter mutations were only detected by ddPCR, and promoter mutations were consistently found at lower concentrations than other driver mutations in longitudinal samples. In vitro experiments revealed that mutations in promoter regions of TERT and DPH3 are underrepresented in ctDNA. While the results underscore the utility of using ctDNA as an alternative to tissue biopsy for genetic profiling and surveillance of the disease, our study highlights the underrepresentation of promoter mutations in ctDNA and its potential impact on quantitative liquid biopsy applications.

Inhibition and switching are executive functions (EFs) that have different developmental trajectories across childhood. The development of specific processes unique to each EF may contribute to these trajectories. Interference suppression and reversal were examined in a large sample of children aged 7 and 9 years (n = 120) and followed-up after two-years to investigate developmental trajectories of inhibition and switching. The N2 and P3b components provided neural correlates of conflict monitoring and attentional processing of conflict involved in interference suppression and reversal. Interference suppression improved over time, however, switching performance did not significantly change between 7 and 11 years. Improvements in correct RT with age and time indicated increased efficiency of stimulus evaluation, response preparation and execution. N2 amplitude decreased with both age and time, indicating less reliance on conflict monitoring to signal cognitive control to manage stimulus and response conflict. P3b amplitude modulations indicated that different amounts of attention were allocated to updating mental representations of interference suppression and reversal task features. These data indicated different developmental trajectories of specific processes unique to inhibition and switching across the childhood period of 7–11 years, providing further empirical evidence that 7–11 years is a critical period for cognitive development. Keywords: Inhibition, Switching, Conflict monitoring, N2, Executive functions, Development

Abstract Background The contribution of beverages to overall diet is of increasing interest to researchers and policymakers, particularly in terms of consumption of drinks high in added sugars; however, few tools to assess beverage intake have been developed and evaluated. This study aimed to evaluate the relative validity of a new online Beverage Frequency Questionnaire (BFQ) among young adults in Canada. Methods A cross-sectional relative validation study was conducted among young adults aged 16–30 years (n = 50). Participants completed a 17-item BFQ, a 7-day food record (7dFR), and a single-item measure of sugary drink intake. Pearson correlations and paired t-tests were used to evaluate correlation and agreement between the measures for 17 individual beverage categories, total drink consumption, total alcoholic beverage consumption, and two definitions of drinks with excess sugars. Cognitive interviews were conducted to examine participant interpretation and comprehensiveness of the BFQ. Results Estimates of beverage intake based on the BFQ and the 7dFR were highly correlated, specifically for the total number and volume of beverages consumed, total alcoholic beverage consumption, sugary drink intake, and each of the 17 beverage categories with 3 exceptions: coffee or tea with sugar or cream, specialty coffees, and hard alcohol with caloric mix. Paired t-tests between the BFQ and the 7dFR indicated that the average reported volume was significantly different only for sweetened fruit drinks. The single-item measure of sugary beverage intake was not significantly correlated with the 7dFR. Cognitive interviewing demonstrated high comprehension levels, and confirmed the appropriateness of the BFQ beverage categories and sizes. Conclusions Overall, the results suggest that the BFQ performed well relative to a 7dFR and had high usability among this study population, indicating its promise for collecting population-level data on beverage intake, including sugar-sweetened beverages, which are known indicators of diet and health.

The current study assessed youth and young adults’ perceptions and attitudes toward caffeine and energy drinks (EDs). An online survey was conducted with 2036 panelists aged 12–24, about caffeine and ED knowledge, caffeine perceptions, and perceptions of ED safety. Few respondents (2.1%) could state Health Canada’s recommended limit for caffeine intake, although most participants (64.9%) correctly stated the maximum number of EDs that should be consumed per day. When shown four beverages, only 17.5% correctly identified the beverage with the most caffeine. Overall, young people generally have low levels of knowledge about caffeine amounts and intake from caffeinated beverages.

Cette étude visait à évaluer les perceptions et les attitudes des adolescents et des jeunes adultes à l’égard de la caféine et des boissons énergisantes. Un sondage en ligne a été mené auprès de 2 036 participants de 12 à 24 ans afin de savoir quelles étaient leurs connaissances sur la caféine et les boissons énergisantes ainsi que leurs perceptions concernant la caféine et l’innocuité des boissons énergisantes. Peu de répondants (2,1 %) ont été en mesure de préciser l’apport maximal en caféine recommandé par Santé Canada, bien que la plupart (64,9 %) aient indiqué sans se tromper le nombre maximal de boissons énergisantes pouvant être consommé quotidiennement. Seulement 17,5 % des répondants ont su repérer, parmi quatre boissons présentées, celle qui contenait le plus de caféine. Dans l’ensemble, les jeunes ont généralement une faible connaissance des quantités de caféine contenues dans les boissons et de l’apport en caféine provenant des boissons caféinées.

The growing market for caffeinated energy drinks (CEDs) has caused concern about excessive caffeine intake and potential adverse effects, particularly among young people. The current study examined patterns of CED consumption among youth and young adults in Canada, using data from a national online survey conducted in October 2014. Data from a non-probability sample of 2040 respondents aged 12–24 from a consumer panel was weighted to national proportions; measures of CED consumption were estimated, including prevalence, excessive daily consumption, and context for use (locations and reasons). Separate logistic regression models for two outcomes, past-week consumption and “ever” exceeding two energy drinks in a day (as per common guidance), were conducted to examine associations with demographic variables (sex, age, geographic region, race/ethnicity, and language). Overall, 73.6% of respondents reported “ever” consuming energy drinks; 15.6% had done so in the past week. Any consumption of energy drinks in the past week was more prevalent among males, Aboriginal respondents (vs. white only or mixed/other), and residents of British Columbia. Among “ever-consumers,” 16.0% reported ever consuming more than two energy drinks in a day. Exceeding two in a day was more prevalent among older respondents (young adults aged 18–24), aboriginal respondents (vs. white only), and British Columbia residents. While the majority of youth and young adults had consumed energy drinks, about half were “experimental” consumers (i.e., consumed ≤5 drinks in their lifetime). Approximately one in six consumers had exceeded the usual guidance for maximum daily consumption, potentially increasing their risk of experiencing adverse effects.

Small bowel obstruction (SBO) is a commonly encountered medical condition, typically a result of extrinsic causes, including post-operative adhesions. Less frequently, intrinsic and intraluminal factors may cause obstruction. Barium sulfate is a widely used contrast agent for radiography of suspected SBO, though it is rarely encountered in histologic sections and is an uncommon cause of SBO. Here, we present a case of a patient with several risk factors for SBO who received routine diagnostic imaging. Surgical resection revealed gross adhesions and histology showed intraluminal foreign material, determined to be barium sulfate by scanning electron microscopy with energy dispersive x-ray spectroscopy. Keywords: Small bowel obstruction, Barium sulfate, Dysmotility

**Background**: Sarcomas comprise a heterogenous group of malignant tumours of mesenchymal origin and can arise in the skin. Definitive management of skin sarcoma usually entails surgical resection with wide margins, often requiring reconstruction. The incidence and demographics of these neoplasms in Australia are poorly understood. **Method**: Incidence, sex and age distribution data for skin sarcomas for the period 1982–2009 were obtained from the Australian Cancer Database (ACD). Morphology and topographical region coding via the International Classification of Diseases for Oncology third edition (ICD-O-3)1 were used to identify the data. **Results**: A total of 5453 cases of skin sarcoma in the Australian population were identified over the 28-year period. Anatomically, 1610 cases (29%) occurred on the limbs, 1416 (26%) on the head and neck area, 957 (18%) on the trunk and 1470 (27%) had an unspecified skin origin. Overall incidence was 2.09 per 100,000 population. Males were more commonly affected (70%), most commonly in the 30–49 years and 70+ years age groups. The most common pathological subtypes were fibromatous sarcoma (including dermatofibrosarcoma protuberans), Kaposi’s sarcoma and pleomorphic dermal sarcoma. **Conclusion**: The Australian Cancer Database data used to describe the pattern and epidemiological trends for skin sarcoma in Australia demonstrated variation from international trends and highlight the need for further research into the aetiology of these tumours.

Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease caused by a pathogenic disruption of the DYSTROPHIN gene that results in non-functional dystrophin protein. DMD patients experience loss of ambulation, cardiac arrhythmia, metabolic syndrome, and respiratory failure. At the molecular level, the lack of dystrophin in the muscle results in myofiber death, fibrotic infiltration, and mitochondrial dysfunction. There is no cure for DMD, although dystrophin-replacement gene therapies and exon-skipping approaches are being pursued in clinical trials. Mitochondrial dysfunction is one of the first cellular changes seen in DMD myofibers, occurring prior to muscle disease onset and progresses with disease severity. This is seen by reduced mitochondrial function, abnormal mitochondrial morphology and impaired mitophagy (degradation of damaged mitochondria). Dysfunctional mitochondria release high levels of reactive oxygen species (ROS), which can activate pro-inflammatory pathways such as IL-1β and IL-6. Impaired mitophagy in DMD results in increased inflammation and further aggravates disease pathology, evidenced by increased muscle damage and increased fibrosis. This review will focus on the critical interplay between mitophagy and inflammation in Duchenne muscular dystrophy as a pathological mechanism, as well as describe both candidate and established therapeutic targets that regulate these pathways.

Salvage logging after a natural disturbance is controversial because it may disrupt forest succession and reduce the value of wildlife habitat, but few studies have examined consequences on predator-prey systems. For herbivores that consume early-seral vegetation, salvage logging may simultaneously improve food abundance and reduce protective cover, imposing trade-offs that influence their habitat selection and that of their predators. We examined habitat use by snowshoe hares (Lepus americanus)—a keystone prey species in the boreal forest—and their primary predators, Canada lynx (Lynx canadensis) and coyotes (Canis latrans), in response to salvage logging following a bark beetle outbreak in Yukon, Canada. We monitored hare, lynx, and coyote presence in beetle-affected forests and salvage-logged stands of different tree retention levels and ages (up to 25 years post-logging) using wildlife cameras, and modelled species occupancy as a function of forest structure at local and landscape scales. Snowshoe hares occupied stands with dense canopies and avoided salvage-logged stands regardless of retention class or age, selecting habitat with the most cover from aerial and terrestrial predators. Lynx and coyote generally used the same habitat as hares, selecting unsalvaged stands with high snowshoe hare occupancy. Habitat use by coyote and hare was more strongly linked than that of lynx and hare, perhaps because coyotes are versatile predators that can adjust their hunting tactics in dense habitat. Our study demonstrates that salvage-logged stands have lower value than beetle-affected forest for snowshoe hares and their predators in the short-term—regardless of retention levels—which may have localized impacts on boreal forest food webs. Higher tree retention, long harvest intervals, and small cut areas interspersed with large unlogged forest patches are recommended to mitigate negative impacts of salvage logging on these species. Keywords: Salvage logging, Boreal forest, Snowshoe hare, Canada lynx, Coyote, Occupancy modelling

The aim of this study was to evaluate the association of contractures, fractures, and deformities in four patients with Bruck syndrome treated in our facility. Data were collected from medical records, radiographs, dual-energy X-ray absorptiometry (DEXA) scans, genetic tests, and gait analysis. All had contractures at birth and genotypic findings including mutations in PLOD2 or FPKB10. Three cases were treated with bisphosphonates with improvement in bone density verified by DEXA. In Bruck syndrome, orthopedic deformities include the following sequential aspects: contractures, characterized by upper and lower extremity contractures such as clubfeet; fractures, characterized by multiple diaphyseal fractures in the long bones of the extremities; and deformities, characterized by malalignment of extremities and the spine. Physical therapy and bracing proved helpful for the contractures to try to stop progression. Bone fragility needs to be considered when deciding to attempt cast correction. Surgeries in the soft tissues can be performed to retain joint movement. In fractures with angulation, intramedullary nail fixation was useful, and in cases without deformity, casting alone was successful. We suggest monitoring the bone density with DEXA, nutrition support with vitamin D and calcium, and treatment with bisphosphonates. Spine deformities were successfully treated by spinal fusion and instrumentation.