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Arthrogryposis multiplex congenita (AMC) is characterized by joint contractures in 2 or more body areas, often resulting in clubfoot deformities that are typically stiffer than those seen in idiopathic clubfoot deformities. While surgery is routinely used to treat clubfoot in AMC, it has a high rate of recurrence and complications. Current literature suggests serial casting (SC) could be useful in treating clubfoot in AMC, though evidence of its effectiveness is limited.Passive range of motion (PROM), dynamic foot pressure, parent-reported Pediatric Outcomes Data Collection Instrument, brace tolerance, and the need for post-casting surgery were evaluated retrospectively in children with AMC treated with SC to address clubfoot deformities. Analysis of variance or paired t tests were used as appropriate on pre-casting, short-term (within 6 mo after SC) and/or longer-term (6 to 18 mo after SC) parameters to determine the effectiveness of SC. Brace tolerance before and after SC was analyzed using the Global Test for Symmetry, and medical records were reviewed to determine the need for surgery post-SC.Forty-six children (6.1±3.1 y old) were cast an average of 2.5±1.9 times, resulting in 206 SC episodes. PROM showed improvement in ankle dorsiflexion and forefoot abduction in the short term (P0.05), returning to baseline measurements in the long term (P=0.09). Brace tolerance improved after casting (P0.05). Only 15% of feet required surgery at follow-up at 10.3±5.5 years. There were no significant changes in dynamic foot pressure or Pediatric Outcomes Data Collection Instrument results after SC, except for an increase in the pain subtest (P0.05).Serial casting in children with AMC can be effective in temporarily improving PROM and improving brace tolerance, but it does not impact dynamic barefoot position. Positive impact of conservative management in children with AMC can potentially delay or reduce the need for invasive surgical intervention by improving PROM and brace tolerance.Level III, Retrospective Comparative Study.

BackgroundThe e-cigarette market has rapidly evolved, with a shift towards higher nicotine concentration and salt-based products, such asJUUL; however, the implications for youth vaping remain unclear.MethodsRepeat cross-sectional online surveys were conducted in 2017, 2018 and 2019, with national samples of youth aged 16–19 years recruited from commercial panels in Canada (n=12 018), England (n=11 362) and the USA (n=12 110). Regression models examined differences between countries and over time in the types of e-cigarette products used (design and nicotine content), reasons for using brands and differences in patterns of use, sociodemographics and dependence symptoms by brand/nicotine content.ResultsIn 2019, the use of pod- or cartridge-style e-cigarettes was greater in Canada and the USA than England, withSmokandJUULthe leading brands in all countries. In 2019, youth vapers in England were less likely to report using e-cigarettes with ≥2% nicotine (12.8%) compared with Canada (40.5%; adjusted OR (AOR)=4.96; 95% CI 3.51 to 7.01) and the USA (37.0%; AOR=3.99, 95% CI 2.79 to 5.71) and less likely to report using nicotine salt-based products (12.3%) compared with Canada (27.1%; AOR=2.77, 95% CI 1.93 to 3.99) and the USA (21.9%; AOR=2.00, 95% CI 1.36 to 2.95). In 2019, self-reported use of products with higher nicotine concentration was associated with significantly greater frequency of vaping, urges to vape and perceived vaping addiction (pConclusionsThe use of high-nicotine salt-based products is associated with greater symptoms of dependence, includingJUULand other higher-nicotine brands. Greater use of high-nicotine salt-based products may account for recent increases in the frequency of vaping among youth in Canada and the USA.

Study Objectives To assess whether the association between insomnia and subclinical myocardial injury, as measured by cardiac troponin T (cTnT), differs across insomnia phenotypes. Methods We measured cTnT in 2188 participants in the Multi-Ethnic Study of Atherosclerosis study who had completed sleep questionnaires and undergone unattended polysomnography (PSG) and 7-day actigraphy. Insomnia symptoms were defined as reporting at least one of the following ≥5 nights/week over the past 4 weeks: trouble falling asleep, waking up several times a night, having trouble getting back to sleep after waking up too early, or taking sleeping pills to help falling asleep. Obstructive sleep apnea (OSA) was defined as an apnea-hypopnea index (AHI >15 events/h). Participants were classified into insomnia phenotypes, including comorbid insomnia and OSA (COMISA) and insomnia associated with actigraphy-estimated short sleep ( Results The mean age was 68.8 (SD 9.2) years, 53.6% were male. In total, 47.8% met threshold levels for insomnia symptoms, and 43.1% had an AHI >15. In adjusted linear regression models COMISA (β 0.08 [standard error (SE) 0.03], p < .01) and insomnia with short sleep duration (β 0.07 [SE 0.03], p < .05) were each associated with higher cTnT compared to a reference group with no insomnia. Insomnia with fragmented sleep (β 0.03 [SE 0.02]) was not associated with higher cTnT (p > .05) in adjusted analyses. OSA was associated with higher cTnT (β 0.09 [SE 0.03], p < .01) in adjusted models. Conclusions COMISA and insomnia with short sleep duration, but not insomnia symptoms alone or fragmented sleep, were associated with increased circulating cTnT in older adults.

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada, Funder: Mitacs, Foresight science is a systematic approach to generate future predictions for planning and management by drawing upon analytical and predictive tools to understand the past and present, while providing insights about the future. To illustrate the application of foresight science in conservation, we present three case studies: identification of emerging risks to conservation, conservation of at-risk species, and aid in the development of management strategies for multiple stressors. We highlight barriers to mainstreaming foresight science in conservation including knowledge accessibility/organization, communication across diverse stakeholders/decision makers, and organizational capacity. Finally, we investigate opportunities for mainstreaming foresight science including continued advocacy to showcase its application, incorporating emerging technologies (i.e., artificial intelligence) to increase capacity/decrease costs, and increasing education/training in foresight science via specialized courses and curricula for trainees and practicing professionals. We argue that failure to mainstream foresight science will hinder the ability to achieve future conservation objectives in the Anthropocene.

Purpose The tobacco and nicotine market is diversifying. Implications for public health will depend on trends in use, including overall use, and who is using these products. This study examined differences over time (2017–2019), across countries (Canada, England, the United States (US)), and by smoking and vaping, in use of other tobacco/nicotine products and overall use. Methods The study includes online repeat cross-sectional surveys of youth aged 16–19 years in Canada (N = 11,714), England (N = 11,170), US (N = 11,838) in 2017, 2018, and 2019. Past 30-day use of tobacco/nicotine products (any, cigarette, e-cigarette, other combusted [cigars/cigarillos/waterpipe], other non-combusted [smokeless tobacco/nicotine replacement therapies) were examined by country, year, and, for other combusted and non-combusted products, past 30-day cigarette smoking and vaping. Use of emerging products (IQOS, nicotine pouches) was explored in 2018–2019. Results From 2017 to 2019, use of any product increased in Canada (17.1%–23.2%, AOR = 1.07 [95% CI = 1.04–1.09]) and the US (18.0%–24.0%, AOR = 1.06 [1.04–1.09]) but not England (20.8%–21.7%, AOR = 1.01 [.99–1.03]). Use of other combusted products (cigars/cigarillos/waterpipe) showed little change (Canada: 8.1%–7.8%; England: 6.3%–7.3%; US: 8.6%–8.5%; p ≥ .151). Use of other non-combusted products (smokeless/nicotine replacement therapies) increased in all countries (Canada: 1.5%–3.2%, AOR = 1.02 [1.01–1.02]; England: 1.4%–2.6%, AOR = 1.02 [1.01–1.03]; US: 3.3%–4.9%, AOR = 1.02 [1.01–1.02]). Vaping increased in all countries (Canada: 8.4%–17.8%; England: 8.7%–12.6%; United States: 11.1%–18.5%; all p Conclusions Youth past 30-day tobacco and nicotine product use increased from 2017 to 2019 in Canada and the United States, largely due to increases in vaping and other non-combusted products. “Other” tobacco/nicotine products were used predominantly by youth who smoked cigarettes and/or vaped.

The civil engineering curriculum in colleges and universities across the United States needs to include information on workplace safety, argued expert panelists during a recent roundtable discussion. Panelists debated how to achieve that goal and learned about the experience of another industry that successfully tackled the same problem.

Mafic-ultramafic plutonic intrusions form an early phase in the emplacement of the predominantly granitic Vioolsdrif Suite, which together with its extrusive carapace, the Orange River Group, form the Richtersveld Magmatic Arc, a Palaeoproterozoic crustal segment formed between 1910 and 1865 Ma. Their lithologic character and distinctive dark weathering features in the mountain desert landscape of the Richtersveld, neighbouring regions of the Northern Cape Province and southern Namibia, make them a separate mappable unit in what is a predominantly granitic terrain. The name of the subsuite is taken from a spectacular twin peak massif near Goodhouse (Vuurdoodberg), while the type locality is one of the best preserved central-type intrusive bodies at Swartkop, situated 2 km off the N7 highway about 20 km south of the border town of Vioolsdrif, where the rock types present include gabbro, metagabbro, quartz-metagabbro, peridotite and troctolite.

A new representative of the Thermosbaenacea, Salishbaena kootenai n. g., n. sp., is described. Based on its specific characteristics and the complexly build maxilla 2, it clearly belongs to the family Halosbaenidae and morphologically seems closest to the European genus Limnosbaena, rather than to the other genera within this family. Updated keys for the identification of the families and genera within the Thermosbaenacea are provided. Given the significant range extension and unusual geologic and biogeographic context that this new record represents within the order Thermosbaenacea, brief observations on habitat and biogeography are included as well.

Background The validity of circulating tumour DNA (ctDNA) as an indicator of disease progression compared to medical imaging in patients with metastatic melanoma requires detailed evaluation. Methods Here, we carried out a retrospective ctDNA analysis of 108 plasma samples collected at the time of disease progression. We also analysed a validation cohort of 66 metastatic melanoma patients monitored prospectively after response to systemic therapy. Results ctDNA was detected in 62% of patients at the time of disease progression. For 67 patients that responded to treatment, the mean ctDNA level at progressive disease was significantly higher than at the time of response (P N = 15). Conclusions These results highlight the low efficacy of ctDNA to detect disease progression in melanoma when compared mainly to standard positron emission tomography imaging.

This study examined reasons why adults who currently smoke or formerly smoked cigarettes use nicotine vaping products (NVPs) by vaping frequency (daily vs. weekly) stratified by smoking status. This cross-sectional study included 3070 adults from the 2020 ITC Four Country Smoking and Vaping Survey (Australia, Canada, England, United States) who reported using a NVP (vaping) at least weekly and who either currently smoke (n = 2467) or formerly smoked (n = 603). Respondents were asked to select the reason(s) they use NVPs, including to manage their smoking (reduce/quit or remain quit) and/or for reasons unrelated to managing smoking (e.g., to save money, enjoyment, flavours). We found that both current and former smokers endorsed an average of six reasons for vaping, with those vaping daily reporting significantly more reasons than those vaping weekly. Among current smokers, 72.8% reported vaping may help them quit smoking, 13.0% reported vaping to reduce smoking but not to quit, and 14.2% reported vaping only for reasons other than to reduce or quit smoking. The most common reason for vaping among current smokers was to reduce smoking (81.3%). Current smokers vaping daily were significantly more likely than those vaping weekly to report using a NVP to reduce smoking, for enjoyment, to reduce harm to themselves and others, to quit smoking, likeable flavours, and to save money. The most common reason cited for vaping by respondents who formerly smoked was enjoyment, with those who vaped daily more likely than those who vaped weekly to report vaping for enjoyment and to reduce harm to themselves. Nearly all reported vaping to help stay abstinent from smoking (92.3%), with no significant difference by vaping frequency. In conclusion, a majority of respondents reported using NVPs to manage their smoking (reduce/quit smoking or remain quit), particularly those vaping daily. Those who were vaping daily also endorsed a greater number of reasons other than managing smoking relative to those who were vaping weekly.

Non-technical skills complement technical skills in surgeons to provide best possible care for patients. The former is essential to promote patient engagement. Coaching has been introduced to surgeons as a method to improve non-technical skills. We aimed to investigate the impact of coaching for surgeons on patient engagement in the outpatient consultation setting.This was a single-centre cohort study conducted in South Australia. Consultant surgeons, suitable coaches, and patients were recruited. Coaches underwent further training by a human factors psychologist on being an effective coach. Outpatient consultations were recorded in an audio-visual format and analysed by investigators. Patient talking time, mutual eye gaze between surgeon and patient, and number of questions asked by the patient were measured as outcomes for patient engagement.182 patients, 12 surgeons, and 4 coaches participated in the study. Each surgeon underwent 3 coaching sessions, 5 to 6 weeks apart. There were 62 pre-coaching patient consultations, 63 patient consultations after one coaching session, and 57 patient consultations after two coaching sessions. The mean talking time of the patient increased significantly after a single coaching session (P 0.05) without making significant difference to the total consultation time (p = 0.76). Coaching sessions did not have a significant effect on mutual eye gaze or mean number of questions asked by the patient.Coaching of non-technical skills for surgeons appears to objectively improve patient engagement during the outpatient consultation. This would suggest that tailored coaching programs should be developed and delivered to surgeons to improve care delivery.

Exercise-induced laryngeal obstruction is a paradoxical laryngeal closure during inspiration at high-intensity exercise, with supraglottic closure being most common. This study develops a model based on the computational fluid dynamics to investigate airflow velocity and pressure and the air-induced loads on the supraglottis at various inspiratory flow rates. It is found that at high flow rates, positive wall pressure is formed in the hypopharynx localise towards its lower region, while posterior supraglottic wall pressures shift from positive to negative. These findings suggest that high inspiratory flow rates may increase supraglottic pressure differentials, ultimately contributing in the collapse.

Introduction. Marketing elements on packaging can influence the appeal of electronic cigarette (EC) products. ECs can contain nicotine and their long-term health effects are unknown; it is important to monitor elements such as packaging which may influence the appeal and uptake of EC products by youth. This study therefore aims to describe marketing elements used on the packaging of commonly used EC products in England, Canada, and the US, countries with different EC marketing regulations. Methods and analysis. We will conduct two content analyses of EC products and their packaging. The first will focus on liquid-containing products (disposable devices, e-liquid refills) in Canada, England, and the US; the second on EC devices (tank, cartridge, and disposable) in England. We will use a codebook to systematically record elements present on EC products and their packaging, including: warnings, product information (e.g., flavour and nicotine), characteristics and design of the packaging and the product (e.g., shape, size), claims (e.g., health-related, cost-related), digital and interactive elements, colours, other graphic elements, and coder impressions. EC products will be sampled based on the most popular brands identified from surveys conducted by the International Tobacco Control Policy Evaluation Project (ITC) and Action on Smoking and Health (ASH). Approximately 144 products will be sampled for the cross-country analysis and 45 for the single-country analysis. We will report frequencies of each element, discuss frequently identified codes, and describe any notable differences between countries and product types. Ethics and dissemination. No ethical concerns. Results will be submitted for publication in a peer-reviewed journal.

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.

BACKGROUND: The prevalence of atrial fibrillation(AF) and diabetes mellitus is rising to epidemic proportions. We aimed to assess the impact of diabetes on the management and outcomes of patients with AF.METHODS: The EORP-AF General Long-Term Registry is a prospective, observational registry from 250 centres across 27 European countries. Outcomes of interest were as follows: i)rhythm control interventions; ii)quality of life; iii)healthcare resource utilisation; and iv)major adverse events.RESULTS: Of 11,028 patients with AF, the median age was 71 (63-77) years and 2537 (23.0%) had diabetes. Median follow-up was 24 months. Diabetes was related to increased use of anticoagulation but less rhythm control interventions. Using multivariable analysis, at 2-year follow-up, patients with diabetes were associated with greater levels of anxiety (p = 0.038) compared to those without diabetes. Overall, diabetes was associated with worse health during follow-up, as indicated by Health Utility Score and Visual Analogue Scale. Healthcare resource utilisation was greater with diabetes in terms of length of hospital stay (8.1 (±8.2) vs. 6.1 (±6.7) days); cardiology and internal medicine/general practitioner visits; and emergency room admissions. Diabetes was an independent risk factor of major adverse cardiovascular event (MACE; HR 1.26 [95% CI, 1.04-1.52]), all-cause mortality (HR 1.28 [95% CI, 1.08-1.52]), and cardiovascular mortality (HR 1.41 [95% CI, 1.09-1.83]).CONCLUSION: In this contemporary AF cohort, diabetes was present in 1 in 4 patients and it served as an independent risk factor for reduced quality of life, greater healthcare resource utilisation and excess MACE, all-cause mortality and cardiovascular mortality. There was increased use of anticoagulation therapy in diabetes but with less rhythm control interventions.

Engineers have played an essential role in preparing cities and states for the 2021 hurricane season. Their efforts to protect the public and public infrastructure range from sea walls to sewer sys...

The Eastern Glades project in Houston has added a new artificial lake and other amenities to the city’s Memorial Park. As a highlight of the park’s 10-year master plan, the multifunction Hines Lake provides the local community with stormwater treatment, flood control protection, aquatic wildlife habitats, recreational facilities, and other benefits.

BACKGROUND: Many studies document associations between low health literacy (HL) and poor health behaviors and outcomes. Yet, HL is understudied among adolescents, particularly from underserved, rural communities. We targeted rural adolescents in this cross-sectional study and explored relationships between HL and (1) energy-balance-related health behaviors and (2) body mass index (BMI) and quality of life (QOL). METHODS: Surveys were administered to 7th graders across 8 middle schools in rural Appalachia. HL was assessed using the Newest Vital Sign. Energy-balance-related behaviors and QOL were assessed using validated instruments. Height and weight were objectively measured. Analyses were conducted using the Hodges-Lehmann nonparametric median difference test. RESULTS: Of the 854 adolescent students (mean age = 12; 55% female), 47% had limited HL. Relative to students with higher HL, students with lower HL reported significantly lower frequency of health-promoting behaviors (water, fruit and vegetable intake, physical activity, sleep), higher frequency of risky health behaviors (sugar-sweetened beverages, junk food, screen time), and had higher BMI percentiles and lower QOL (all p < .05). CONCLUSIONS: Low HL is associated with energy-balance-related behaviors, BMI, and QOL among rural, Appalachian adolescents. Findings underscore the relevance of HL among rural middle school students and highlight implications for school health.

Limb length discrepancy (LLD) is common in both the pediatric and adult population. Length inequalities can be due to a multitude of etiologies including congenital, developmental, and acquired causes. There has been little consensus on the morbidity of LLD and, as a result, the threshold necessary for treatment of LLD to prevent morbidity. Advances in magnetically controlled lengthening devices achieve greater accuracy and patient satisfaction and create an opportunity to lower the threshold for limb lengthening.Asymptomatic LLD is relatively common in both pediatric and adult populations. Only ~10% of the population has equal leg length. LLD of5 cm may lead to long-term morbidities such as scoliosis, lower back pain, gait abnormalities, stress on hip or knee joint, and lower extremity symptomatic versus asymptomatic osteoarthritis. The teaching in most orthopaedic textbooks is to adjust the shoe if symptomatic for discrepancies up to 2 cm; consider an orthotic, epiphysiodesis, or skeletal shortening for 2.5 to 5 cm; and possible limb reconstruction for5 cm. The assumption is that there are no long-term consequences of mild LLD. However, data in recent literature show that small discrepancies may contribute to pathologic changes such as pain, gait abnormalities, and osteoarthritis. Major advances have been made in limb lengthening over the past 40 years. The increased accuracy and superior patient satisfaction of the magnetically controlled lengthening nail versus external fixation methods argue for including lengthening for LLD of5 cm.If mild LLD can cause long-term pathology, it is important to counsel families on the full range of options for limb equalization no matter the size of the discrepancy. The evolution in technology and understanding of limb lengthening has provided additional safe surgical options. Therefore, the historic treatment protocol for addressing limb differences may need to include lengthening for smaller discrepancies even2 cm.

The first phase of the Silicon Valley Extension Program expanded heavyrail transit service in Northern California from the San Francisco Bay Area southward into the Silicon Valley. The $2.3-billion...

Venous invasion (VI) is a powerful prognostic factor in colorectal cancer (CRC) that is widely underreported. The ability of elastin stains to improve VI detection is now recognized in several international CRC pathology protocols. However, concerns related to the cost and time required to perform and evaluate these stains in addition to routine hematoxylin and eosin (HE) stains remains a barrier to their wider use. We therefore sought to determine whether an elastin trichrome (ET) stain could be used as a "stand-alone" stain in CRC resections, by comparing the sensitivity, accuracy, and reproducibility of detection of CAP-mandated prognostic factors using ET and HE stains. Representative HE- and ET-stained slides from 50 CRC resections, including a representative mix of stages and prognostic factors, were used to generate 2 study sets. Each case was represented by HE slides in 1 study set and by corresponding ET slides from the same blocks in the other study set. Ten observers (3 academic gastrointestinal [GI] pathologists, 4 community pathologists, 3 fellows) evaluated each study set for CAP-mandated prognostic factors. ET outperformed HE in the assessment of VI with respect to detection rates (50% vs. 28.6%; P0.0001), accuracy (82% vs. 59%, P0.0001), and reproducibility (k=0.554 vs. 0.394). No significant differences between ET and HE were observed for other features evaluated. In a poststudy survey, most observers considered the ease and speed of assessment at least equivalent for ET and HE for most prognostic factors, and felt that ET would be feasible as a stand-alone stain in practice. If validated by others, our findings support the use of ET, rather than HE, as the primary stain for the evaluation of CRC resections.

Introduction RNA-binding proteins (RBPs) play an important role in skeletal muscle development and disease by regulating RNA splicing. In myotonic dystrophy type 1 (DM1), the RBP MBNL1 (muscleblind-like) is sequestered by toxic CUG repeats, leading to missplicing of MBNL1 targets. Mounting evidence from the literature has implicated other factors in the pathogenesis of DM1. Herein we sought to evaluate the functional role of the splicing factor hnRNP L in normal and DM1 muscle cells. Methods Co-immunoprecipitation assays using hnRNPL and MBNL1 expression constructs and splicing profiling in normal and DM1 muscle cell lines were performed. Zebrafish morpholinos targeting hnrpl and hnrnpl2 were injected into one-cell zebrafish for developmental and muscle analysis. In human myoblasts downregulation of hnRNP L was achieved with shRNAi. Ascochlorin administration to DM1 myoblasts was performed and expression of the CUG repeats, DM1 splicing biomarkers, and hnRNP L expression levels were evaluated. Results Using DM1 patient myoblast cell lines we observed the formation of abnormal hnRNP L nuclear foci within and outside the expanded CUG repeats, suggesting a role for this factor in DM1 pathology. We showed that the antiviral and antitumorigenic isoprenoid compound ascochlorin increased MBNL1 and hnRNP L expression levels. Drug treatment of DM1 muscle cells with ascochlorin partially rescued missplicing of established early biomarkers of DM1 and improved the defective myotube formation displayed by DM1 muscle cells. Discussion Together, these studies revealed that hnRNP L can modulate DM1 pathologies and is a potential therapeutic target.

To keep traffic moving safely and efficiently, engineers are increasingly turning to the modern roundabout, an upgrade on the traditional design that its supporters say is safer and more efficient ...

Drug-delivery technologies for modified drug release have been in existence for decades, but their utilization has been largely limited to post-launch efforts improving therapeutic outcomes. Recently, they have gained renewed importance because the pharmaceutical industry is steadily shifting to a more integrated discovery-development approach. In discovery, modulating target engagement via drug-delivery technologies can enable crucial pharmacological studies for building well-defined criteria for molecular design. In development, earlier implementation of delivery technologies can enhance the value of drug products through reduced dosing frequency and improved tolerability and/or safety profile, thereby leading to better adherence and therapeutic effectiveness.

Research Findings: The present study examined patterns of executive function (EF) development among socio-demographically diverse children in kindergarten, first grade, and second grade. Using nati...

ObjectiveThe current study examined indicators of dependence among youth cigarette smokers and e-cigarette users in Canada, England and the USA, including changes between 2017 and 2019.MethodsData are from repeated cross-sectional online surveys conducted in 2017, 2018 and 2019 with national samples of youth aged 16–19 years, in Canada (n=12 018), England (n=11 362) and the USA (n=12 110). Measures included perceived addiction to cigarettes/e-cigarettes, frequency of experiencing strong urges to smoke/use an e-cigarette, plans to quit smoking/using e-cigarettes and past attempts to quit. Logistic regression models were fitted to examine differences between countries and changes over time.ResultsThe proportion of ever-users who vaped frequently was significantly higher in 2019 compared with 2017 for all outcomes in each country. Between 2017 and 2019, the proportion of past 30-day vapers reporting strong urges to vape on most days or more often increased in each country (Canada: 35.3%, adjusted OR (AOR) 1.69, 95% CI 1.20 to 2.38; England: 32.8%, AOR 1.55, 1.08 to 2.23; USA: 46.1%, AOR 1.88, 1.41 to 2.50), along with perceptions of being ‘a little’ or ‘very addicted’ to e-cigarettes (Canada: 48.3%, AOR 1.99, 1.44 to 2.75; England: 40.1%, AOR 1.44, 1.03 to 2.01; USA: 53.1%, AOR 1.99, 1.50 to 2.63). Indicators of dependence among smokers were consistently greater than e-cigarette users, although differences had narrowed by 2019, particularly in Canada and the USA.ConclusionsPrevalence of dependence symptoms among young e-cigarette users increased between 2017 and 2019, more so in Canada and the USA compared with England. Dependence symptom prevalence was lower for e-cigarettes than smoking; however, the gap has narrowed over time.

To describe characteristics and outcomes of Māori and European patients admitted to New Zealand intensive care units (ICUs) between 2009 and 2018.A retrospectively designed prospective cohort study. New Zealand Ministry of Health National Minimum Dataset matched to the Australia New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database. The primary outcome was day-180 mortality. Secondary outcomes were ICU mortality, hospital mortality, discharge to home, ICU length of stay, hospital length of stay and survival time. We report associations between Māori ethnicity and each outcome, with European as the reference category, using regression analyses to adjust sequentially for site, deprivation status, sex, year of admission, the Charlson comorbidity index, age, admission source and type, ICU admission diagnosis, ventilation status and illness severity based on physiological parameters.Māori admitted to ICU were on average 13 years younger than European patients. A total of 968 of 9,681 (10%) Māori and 2,732 of 42,871 (5.2%) European patients were admitted after trauma, and 740 of 9,681 (7.6%) and 2,318 of 42,871 (4.4%) were admitted with sepsis respectively. A total of 1,550 of 9,681 (16.0%) Māori and 6,407 of 42,871 (14.9%) European patients died within 180 days of ICU admission; odds ratio (OR) 1.08; 95% CI, 1.02 to 1.15. When adjusted for age, the OR for day-180 mortality for Māori versus European patients increased substantially. The OR decreased after adjustment for admission source and type, and after accounting for Māori having a higher comorbidity index and more severe illness than European patients. In the final model, incorporating adjustment for all specified variables, Māori ethnicity was not associated with day-180 mortality (adjusted OR 1.01; 95%CI, 0.92 to 1.10). Findings were similar for all secondary outcomes.Compared to European patients, Māori were markedly more likely to be admitted to the ICU after trauma or with sepsis. Despite Māori being on average 13 years younger at ICU admission than their European counterparts, they had more co-morbidities, higher illness severity and a higher risk of dying within 180 days.

Background: Glucose transport from blood to interstitial fluid impacts performance of interstitially-placed continuous glucose monitoring (CGM) sensors. We examined time series offsets (“lag times”) of the G7 CGM system (Dexcom) . Methods: In a pivotal accuracy study conducted in the US, 316 adults with diabetes wearing 6sensors participated in clinic sessions that included glucose manipulations and frequent venous plasma glucose (YSI) determinations. G7 values were obtained every 5 min and interpolated to provide values at 1-min intervals. Each YSI value was associated with 21 G7 values obtained from min before to min after. The absolute relative difference (ARD) was calculated for each YSI:G7 pair and each sensor’s lag was estimated as the time with the lowest mean ARD. Results: A lag time of 2 minutes provided the lowest mean ARD of 8.6% and the highest %20/20 agreement rate of 94.4%. The Figure shows summary statistics for the distribution of sensor-specific lag times. Lag times of ≤0 min (where interstitial glucose leads blood glucose) were observed for 2 (33.0%) of the sensors. Conclusions: The distribution of G7 time series offsets suggests that CGM values may most accurately reflect previous or upcoming blood glucose values. This finding is likely due to technological innovations in G7’s hardware and algorithm. The minimal lag time observed should provide users with confidence in using CGM to manage their diabetes. Disclosure X.Zhang: Employee; Dexcom, Inc. J.L.Reid: Employee; Dexcom, Inc., GenMark Diagnostics. T.C.Walker: Employee; Dexcom, Inc., Stock/Shareholder; Dexcom, Inc. J.Welsh: Employee; Dexcom, Inc. A.Balo: Employee; Dexcom, Inc. Funding Dexcom, Inc.

Objective:The objective of the current study was to identify factors across the socio-ecological model (SEM) associated with adolescents’ sugar-sweetened beverage (SSB) intake.Design:This cross-sectional study surveyed adolescents using previously validated instruments. Analyses included descriptive statistics, ANOVA tests and stepwise nonlinear regression models (i.e., two-part models) adjusted to be cluster robust. Guided by SEM, a four-step model was used to identify factors associated with adolescent SSB intake – step 1: demographics (i.e., age, gender), step 2: intrapersonal (i.e., theory of planned behaviour (attitudes, subjective norms, perceived behavioural control, behavioural intentions), health literacy, media literacy, public health literacy), step 3: interpersonal (i.e., caregiver’s SSB behaviours, caregiver’s SSB rules) and step 4: environmental (i.e., home SSB availability) level variables.Setting:Eight middle schools across four rural southwest Virginia counties in Appalachia.Participants:Seven hundred ninety seventh grade students (55·4 % female, 44·6 % males, mean age 12 (sd0·5) years).Results:Mean SSB intake was 36·3 (sd42·5) fluid ounces or 433·4 (sd493·6) calories per day. In the final step of the regression model, seven variables significantly explained adolescent’s SSB consumption: behavioural intention (P< 0·05), affective attitude (P< 0·05), perceived behavioural control (P< 0·05), health literacy (P< 0·001), caregiver behaviours (P< 0·05), caregiver rules (P< 0·05) and home availability (P< 0·001).Conclusions:SSB intake among adolescents in rural Appalachia was nearly three times above national mean. Home environment was the strongest predictor of adolescent SSB intake, followed by caregiver rules, caregiver behaviours and health literacy. Future interventions targeting these factors may provide the greatest opportunity to improve adolescent SSB intake.

A series of breakwaters to protect a coastal wildlife refuge in southwestern Louisiana incorporated an innovative, lightweight design. Despite extremely poor soils and ongoing erosion that kept changing the shoreline throughout the project, the breakwaters are already showing dramatic results.

This case series examines the spectrum of imaging findings at chest radiography, US, CT, and MRI in 35 children admitted to a tertiary pediatric hospital in April and May 2020 with a post–coronavirus disease 2019 inflammatory condition known as multisystem inflammatory syndrome in children. The constellation of findings includes airway inflammation and rapid development of pulmonary edema on thoracic images, coronary artery aneurysms, and extensive right iliac fossa inflammatory changes on abdominal images. Awareness of this emerging condition and the expected multi-organ imaging findings will aid radiologists in the assessment of these complex cases. © RSNA, 2020

Purpose: We evaluated the predictive value of pretreatment ctDNA to inform therapeutic outcomes in patients with metastatic melanoma relative to type and line of treatment. Experimental Design: Plasma circulating tumor DNA (ctDNA) was quantified in 125 samples collected from 110 patients prior to commencing treatment with immune checkpoint inhibitors (ICIs), as first- (n = 32) or second-line (n = 27) regimens, or prior to commencing first-line BRAF/MEK inhibitor therapy (n = 66). An external validation cohort included 128 patients commencing ICI therapies in the first- (N = 77) or second-line (N = 51) settings. Results: In the discovery cohort, low ctDNA (≤20 copies/mL) prior to commencing therapy predicted longer progression-free survival (PFS) in patients treated with first-line ICIs [HR, 0.20; 95% confidence interval (CI) 0.07–0.53; P < 0.0001], but not in the second-line setting. An independent cohort validated that ctDNA is predictive of PFS in the first-line setting (HR, 0.42; 95% CI, 0.22–0.83; P = 0.006), but not in the second-line ICI setting. Moreover, ctDNA prior to commencing ICI treatment was not predictive of PFS for patients pretreated with BRAF/MEK inhibitors in either the discovery or validation cohorts. Reduced PFS and overall survival were observed in patients with high ctDNA receiving anti–PD-1 monotherapy, relative to those treated with combination anti–CTLA-4/anti–PD-1 inhibitors. Conclusions: Pretreatment ctDNA is a reliable indicator of patient outcome in the first-line ICI treatment setting, but not in the second-line ICI setting, especially in patients pretreated with BRAF/MEK inhibitors. Preliminary evidence indicated that treatment-naïve patients with high ctDNA may preferentially benefit from combined ICIs.

New York City's new arts center, The Shed, features a 120 ft tall, steel-framed shell clad in translucent cushions that rolls out from around a fixed building to cover the adjacent public plaza, cr...