Search

Background: Autism spectrum disorder (ASD) is a lifelong disorder, beginning in early childhood, which often accompanies with several healthcare challenges. There is a need for consistent and continued healthcare services throughout the life of an individual with ASD. The majority of previous studies have examined healthcare services in children with ASD and there is limited evidence about healthcare needs of adults with ASD., Objective: The aim of this project was to capture the experiences of stakeholders including adults with ASD in receiving healthcare services., Method: We interviewed 22 stakeholders, including adults with ASD (n = 13), parents of adults with ASD (n = 5), and service providers (n = 4). Open-ended questions were used to explore their experiences with the healthcare system. We analysed the data thematically to develop the overarching themes., Results: Three themes emerged from interviews including a) availability and accessibility of healthcare services, b) provision of quality healthcare and service delivery, and c) striving for better health outcomes., Conclusion: This study found that many adults with ASD can experience a continued lack of access to services and the care they receive is often of limited quality. The unmet healthcare needs lead stakeholders to feel stress, frustration, exhaustion, and possible burnout. The detrimental cost of limited services not only impacts adults with ASD but also their caregivers., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The COVID-19 pandemic has forced rapid digital transformation of many health systems. These innovations are now entering the literature, but there is little focus on the resulting disruption., Objective: We describe the implementation of digital innovations during the COVID-19 response of Australia's largest health service, Metro North (in Brisbane, Queensland), the challenges of the subsequent digital disruption, how these were managed, and lessons learned., Methods: Prior to the COVID-19 pandemic, the Australian state of Queensland created the Queensland Digital Clinical Charter, which provides guidance for the development of digital health programs. The guidelines utilize three horizons: digitizing workflows, leveraging digital data to transform clinical care, and reimagining new and innovative models of care. The technical response to COVID-19 in Metro North is described across these horizons. The rapid digital response caused significant disruption to health care delivery; management of the disruption and the outcomes are detailed. This is a participatory action research project, with members of the research team assisting with leading the implementation project informing the case report content., Results: Several digital innovations were introduced across Metro North during the COVID-19 response. This resulted in significant disruption creating digital hypervigilance, digital deceleration, data discordance, and postdigital "depression." Successful management of the digital disruption minimized the negative effects of rapid digital transformation, and contributed to the effective management of the pandemic in Queensland., Conclusion: The rapid digital transformation in Metro North during COVID-19 was successful in several aspects; however, ongoing challenges remain. These include the need to improve data sharing and increase interoperability. Importantly, the innovations need to be evaluated to ensure that Metro North can capitalize on these changes and incorporate them into long-term routine practice. Moving forward, it will be essential to manage not only the pandemic, but increasingly, the resultant digital disruption., Competing Interests: None declared., (Thieme. All rights reserved.)

The establishment of genomics in health care systems has been occurring for the past decade. It is recognised that implementing genomics within a health service is challenging without a system-wide approach. Globally, as clinical genomics implementation programs have matured there is a growing body of information around program design and outcomes. Program structures vary depending on local ecosystems including the health system, politics and funding availability, however, lessons from other programs are important to the design of programs in different jurisdictions. Here we describe an adaptive approach to the implementation of genomics into a publicly funded health care system servicing a population of 5.1 million people. The adaptive approach enabled flexibility to facilitate substantial changes during the program in response to learnings and external factors. We report the benefits and challenges experienced by the program, particularly in relation to the engagement of people and services, and the design of both individual projects and the program as a whole., (© 2021. The Author(s).)

Purpose: The expected intensity of pain resulting from a noxious stimulus has been observed to have a strong influence on the pain that is perceived. The neural basis of pain reduction, as a result of expecting lower pain, was investigated using functional magnetic resonance imaging (fMRI) in the brainstem and spinal cord., Methods: Functional MRI studies were carried out in a region spanning the brainstem and cervical spinal cord in healthy participants. Participants were familiarized with a noxious heat stimulus and study procedures in advance, and were informed during each trial that either a heat calibrated to produce moderate pain (Base state), or a temperature 1 °C lower (Low state), would be applied to their hand. However, the Base temperature was applied in every trial., Results: Pain ratings were significantly reduced as a result of expecting lower temperatures. FMRI results demonstrate blood oxygenation-level dependent (BOLD) signal variations in response to participants being informed of the stimulus to expect, in advance of stimulation, and in response to stimulation. Significant coordination of BOLD signals was also detected across specific brainstem and spinal cord regions, with connectivity strengths that varied significantly with the study condition, and with individual pain ratings. The results identify regions that are known to be involved with arousal and autonomic regulation., Conclusions: Expectation-based analgesia is mediated by descending regulation of spinal cord nociceptive responses. This regulation appears to be related to arousal and autonomic regulation, consistent with the cognitive/affective dimension of pain., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Inc.)

Background: The Get Outside: After School Activity Program (GO-ASAP) exemplifies how a rural community can utilize its natural resources and community partnerships to promote adolescent health., Methods: A qualitative descriptive inquiry was conducted using convenience sampling. Data were collected from students ( n = 13/2018; n = 13/2019) via focus group and art-based method (2018 only) and parent ( n = 6/2018) focus group. Data were analyzed via qualitative content analysis using the applied theoretical frameworks of Social Cognitive Theory and Social Determination Theory., Results: (1) Increasing Health-Related Competencies. Students increased their physical activity, improved their sleep, perceived less stress, and reported changes in dietary habits and electronic use. (2) Increasing Social Relatedness. Students made new friends, felt more connected, and spent less time home alone after school. (3) Increasing Autonomy and Intrinsic Motivation. Students recognized their emerging capabilities, and their increased confidence stimulated more action-oriented behavior. Parent-perceived changes support and mirror student reports., Conclusion: Outdoor, nature-based, activity programs are a novel upstream approach to promote adolescent health, especially in rural communities where natural resources often exceed health-service resources and community partnerships are a way of life.

Objective: To examine the degree to which Canadian consensus guideline recommendations for annual comprehensive preventive care assessments of adults with intellectual and developmental disabilities (IDD) are being taken up by Nova Scotia family physicians since the introduction of incentive billing codes; and to discuss the importance of complete physical examinations for this patient population, extra time needed in clinic encounters, and challenges for practitioners providing care., Design: Analysis of family physicians' billing of codes 03.04C and 03.03E from April 2012 to December 2016., Setting: Nova Scotia., Participants: Family physicians., Main Outcome Measures: Number of billings through fee-for-service and alternative payment plans, and number of providers who used these fee codes., Results: Analysis yielded 3 key results. Use of incentivized billing codes for adult IDD visits and complete examinations in Nova Scotia has steadily increased for patients since the introduction of the modified codes. There is measurable uptake of the IDD adult visit code in total numbers and numbers of providers billing the code. There is poor uptake of the complete examination code., Conclusion: Enhanced billing codes will provide Nova Scotia family physicians with an incentive to employ the newly revised 2018 Canadian consensus guidelines in the care of adults with IDDs. With continued discussion and promotion of annual physical examinations for patients with IDD, more patients and caregivers might make this proactive care item a priority., (Copyright © the College of Family Physicians of Canada.)

Aim: To identify the breast cancer specific survival (BCSS) associated with nodal metastasis identified by axillary core biopsy (ACB), and by sentinel node biopsy (SNB) compared with node negative patients. A further aim was to assess the prognostic effects of axillary ultrasound (US) features and amount of tumour in ACB specimens., Methods: Consecutive patients with cancer were identified from a database of US lesions undergoing breast biopsy. The three study groups were: a) those with metastasis identified by ACB, b) those undergoing immediate surgery with positive SNB and c) those undergoing immediate surgery with a negative SNB. US features and the amount of tumour in the ACB specimen were assessed by review of US images and pathological reports. BCSS was assessed using Kaplan Meier survival curves., Results: 967 patients were included, with mean follow-up of 6.0 yrs. There were 90 breast cancer deaths: 26% of those with a positive ACB, 11% with a positive SNB and 4% of those with a negative SNB. BCSS was significantly different between the groups (p < 0.001) with hazard ratio, compared with the negative SNB group, of 7.8 (95% CI 4.4-13.7) for patients with positive ACB and 2.5 (95% CI 1.3-4.6) for positive SNB. Axillary US findings and assessment of the amount of tumour in the ACB did not influence survival., Conclusion: This study suggests that women with a positive ACB have a worse BCSS compared to those with a positive SNB. This should be borne in mind when systemic therapy is being considered., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Infection with the SARS-CoV-2 virus affects a wide range of systems. Significant involvement of the central nervous system has been described, including ischemic and hemorrhagic strokes. Thus far, neuropathologic reports of patients who passed away from COVID-19 have generally described non-specific findings, such as variable reactive gliosis and meningeal chronic inflammatory infiltrates, as well as the consequences of the infection's systemic complications on the brain, including ischemic infarcts and hypoxic/ischemic encephalopathy. The neuropathological changes in patients with COVID-19 and large hemorrhagic strokes have not been described in detail. We report the case of an elderly male who had a long course of COVID-19 and ultimately passed away from a large intracerebral hemorrhage. In addition to acute hemorrhage, neuropathologic examination demonstrated non-specific reactive changes and chronic periventricular lesions with macrophagic and perivascular lymphocytic infiltrates without evidence of demyelination or presence of SARS-CoV-2 by PCR test. This manuscript expands the spectrum of reported neuropathological changes in patients with COVID-19.

Background: Queensland, Australia has been successful in containing the COVID-19 pandemic. Underpinning that response has been a highly effective virus containment strategy which relies on identification, isolation, and contact tracing of cases. The dramatic emergence of the COVID-19 pandemic rendered traditional paper-based systems for managing contact tracing no longer fit for purpose. A rapid digital transformation of the public health contact tracing system occurred to support this effort., Objectives: The objectives of the digital transformation were to shift legacy systems (paper or standalone electronic systems) to a digitally enabled public health system, where data are centered around the consumer rather than isolated databases. The objective of this paper is to outline this case study and detail the lessons learnt to inform and give confidence to others contemplating digitization of public health systems in response to the COVID-19 pandemic., Methods: This case study is set in Queensland, Australia. Universal health care is available. A multidisciplinary team was established consisting of clinical informaticians, developers, data strategists, and health information managers. An agile "pair-programming" approach was undertaken to application development and extensive change efforts were made to maximize adoption of the new digital workflows. Data governance and flows were changed to support rapid management of the pandemic., Results: The digital coronavirus application (DCOVA) is a web-based application that securely captures information about people required to quarantine and creates a multiagency secure database to support a successful containment strategy., Conclusion: Most of the literature surrounding digital transformation allows time for significant consultation, which was simply not possible under crisis conditions. Our observation is that staff was willing to adopt new digital systems because the reason for change (the COVID-19 pandemic) was clearly pressing. This case study highlights just how critical a unified purpose, is to successful, rapid digital transformation., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Focused objectives provide effective learning. Pediatric residents in Canada follow objectives set by the Royal College of Physicians and Surgeons of Canada (RCPSC) with the goal of becoming competent general pediatricians. During the gastroenterology rotation, it remains unclear as to what clinical problems listed in the aforementioned objectives are crucial to understand as part of general pediatric practice. The purpose of this study was to identify the gastroenterological conditions of most importance to incorporate into a focused curriculum for pediatric residents., Methods: All pediatricians across four Canadian Atlantic provinces were surveyed by a mailed questionnaire. Questions included demographics and ranking of the 14 clinical problems currently listed in the RCPSC objectives along with six more generated after input was gained from pediatric gastroenterologists., Results: Of the 234 pediatricians surveyed, 132 (56%) responded, 48% of whom were general pediatricians. Celiac disease, gastroesophageal reflux, and obesity (currently not on the RCPSC list) were identified as important/very important conditions to understand by 94.4%, 96.1%, and 96.0% of respondents, respectively. There were no significant differences in rankings between general pediatricians and subspecialists. A large majority recommended that a rotation in gastroenterology be mandatory during pediatric residency., Conclusions: Pediatricians from four Canadian Atlantic provinces recommended a list of gastrointestinal conditions to be included in pediatric residency training. It would be important to consider these recommendations to keep the training curriculum in sync with real world needs., Competing Interests: There are no conflicts of interest to declare by any of the authors., (© 2021 McNeil, Rashid; licensee Synergies Partners.)

The limited capacity of secondary health services to address the increasing prevalence of dementia within the community draws attention to the need for an enhanced role for nurses working collaboratively with GPs in diagnosing and coordinating post-diagnostic care for patients with dementia. This study investigated the feasibility and acceptability of a nurse practitioner-led mobile memory clinic that was embedded within general practice and targeted to caring for patients and their carers in areas of socioeconomic disadvantage with poor access to specialist health services. Over the period from mid-2013 to mid-2014, 40 GPs referred 102 patients, with the nurse practitioner conducting assessments with 77 of these patients in their homes. Overall, there was a strong interest in this model of care by general practice staff, with the assessment and care provided by the nurse practitioner evaluated as highly acceptable by both patients and their carers. Nonetheless, there are financial and structural impediments to this model of care being implemented within the current Australian health service framework, necessitating further research investigating its cost-effectiveness and efficacy.

Background: The Comprehensive Osteopathic Medical Licensing Examination of the United States Level 1 (COMLEX 1) is important for medical students to be able to graduate. There is a glaring need to identify students who are at a significant risk of performing poorly on COMLEX 1 as early as possible so that extra assistance can be provided to those students. Our goal is to produce a reliable predictive model to identify students who are at risk of scoring lower than 500 on COMLEX 1 at the earliest possible time., Methods: Academic data from medical students who matriculated at Rocky Vista University College of Osteopathic Medicine between 2011 and 2017 were obtained. Odds ratios were used to assess the predictors for scoring lower than 500 on COMLEX 1. Correlation with COMLEX 1 scores was assessed with Pearson correlation coefficient. The predictive models were developed by multiple logistic regression, backward logistic regression, and logistic regression with average scores in courses in the first three semesters, and were based on performances on the Medical College Admissions Test (MCAT) before admission, as well as students' performances in preclinical courses during the first three semesters. The models were generated in about 82% of the student performance data and were then validated in the remaining 18% of the data., Results: Odds ratios showed that MCAT scores and final grades in each course in the first three semesters were significant in predicting a score lower than 500 on COMLEX 1. Performances in third-semester courses including Renal System II, Cardiovascular System II, and Respiratory System II were most important in prediction. The three predictive models had sensitivities of 65.8 -71%, and specificities of 83.2 - 88.2% in predicting a score lower than 500 on COMLEX 1., Conclusions: Lower MCAT scores and lower grades in the first three semesters of medical school predict scoring lower than 500 on COMLEX 1. Students who are identified at risk by our models will have a 65.8 -71% chance of actually scoring lower than 500 on COMLEX 1. Those students will have enough time to receive assistance before taking COMLEX 1.

The ice arches that usually develop at the northern and southern ends of Nares Strait play an important role in modulating the export of Arctic Ocean multi-year sea ice. The Arctic Ocean is evolving towards an ice pack that is younger, thinner, and more mobile and the fate of its multi-year ice is becoming of increasing interest. Here, we use sea ice motion retrievals from Sentinel-1 imagery to report on the recent behavior of these ice arches and the associated ice fluxes. We show that the duration of arch formation has decreased over the past 20 years, while the ice area and volume fluxes along Nares Strait have both increased. These results suggest that a transition is underway towards a state where the formation of these arches will become atypical with a concomitant increase in the export of multi-year ice accelerating the transition towards a younger and thinner Arctic ice pack.

Studies of the neural basis of human pain processing present many challenges because of the subjective and variable nature of pain, and the inaccessibility of the central nervous system. Neuroimaging methods, such as functional magnetic resonance imaging (fMRI), have provided the ability to investigate these neural processes, and yet commonly used analysis methods may not be optimally adapted for studies of pain. Here we present a comparison of model-driven and data-driven analysis methods, specifically for the study of human pain processing. Methods are tested using data from healthy control participants in two previous studies, with separate data sets spanning the brain, and the brainstem and spinal cord. Data are analyzed by fitting time-series responses to predicted BOLD responses in order to identify significantly responding regions (model-driven), as well as with connectivity analyses (data-driven) based on temporal correlations between responses in spatially separated regions, and with connectivity analyses based on structural equation modeling, allowing for multiple source regions to explain the signal variations in each target region. The results are assessed in terms of the amount of signal variance that can be explained in each region, and in terms of the regions and connections that are identified as having BOLD responses of interest. The characteristics of BOLD responses in identified regions are also investigated. The results demonstrate that data-driven approaches are more effective than model-driven approaches for fMRI studies of pain., Competing Interests: The authors have declared that no competing interests exist.

Introduction: JAK2 V617F mutation is one of the major criteria in the diagnosis of myeloproliferative neoplasms (MPN) and its variant allele fraction (VAF) determines the disease phenotype and outcomes. This study aimed to define characteristics and outcomes of patients with JAK2 V617F VAF < 2% compared to patients with VAF 2%-10%., Patients and Methods: We included 5079 patients with JAK2 V617F tested during 2010-2015 and identified 216 patients (4.3%) with JAK2 V617F VAF < 10%. Twenty-seven patients were excluded because of missing follow-up data., Results: A total of 189 patients were included for final analysis (89 patients with VAF < 2% and 100 patients with VAF 2%-10%). Patients with JAK2 V617F 2%-10% VAF had a significantly higher rate of splenomegaly, higher platelet counts, and more MPN diagnoses than the group with VAF < 2%. Ten patients (10.0%) with VAF 2%-10% and 24 patients (27.0%) with VAF < 2% had normal blood count and no thrombosis. There were no differences between the groups in all outcomes, including thrombotic complications (18.0% in both groups), progression to hematologic or solid cancers, and death. Patients without hematologic diagnosis had similar thrombotic incidence (16.7% in VAF < 2% vs. 20.0% in VAF 2%-10%)., Conclusion: Patients with JAK2 V617F mutation VAF < 2% have similar survival and thrombotic incidence as patients with VAF 2%-10%. Patients with low VAF should be monitored in the same manner as patients with higher VAF with the same diagnoses to prevent morbidity and mortality. Patients without hematologic diagnosis may benefit from thrombotic risk reduction strategies such as optimization of cardiovascular risk factors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Digital transformation of Australian hospitals is occurring rapidly. Although the clinical community has had limited ability to influence high-level decision making and investments into digital health technologies, as these technologies increasingly transform the way patients are cared for, the clinical community must influence the digital health agenda and be an integral part of the decision-making process. This case study details the process and lessons learnt during the development of the state-wide consensus statement detailing the clinical requirements for digital health initiatives to form the Queensland Digital Health Clinical Charter. To the best of our knowledge, Queensland is the first Australian jurisdiction to create a Digital Clinical Charter to be specifically referenced in the investment in and governance of digital health in hospitals. By developing this clinical charter for digital health, and in articulating the needs of clinicians, a clinical framework will be added to both the decision-making process around the investments in digital health and the definition and realisation of the expected benefits from these sizable investments.

Background: EGFR T790M testing is the standard of care for activating EGFR mutation (EGFRm) non-small cell lung cancer (NSCLC) progressing on 1st/2nd generation TKIs to select patients for osimertinib. Despite sensitive assays, detection of circulating tumour deoxyribonucleic acid (ctDNA) is variable and influenced by clinical factors. The number and location of sites of progressive disease at time of testing were reviewed to explore the effect on EGFR ctDNA detection. The prognostic value of EGFR ctDNA detection on survival outcomes was assessed., Methods: Following extraction of cell-free DNA from plasma using the QIAamp Circulating Nucleic Acid Kit, custom droplet digital polymerase chair reaction (ddPCR) assays were used to assess EGFR ctDNA using the Bio-Rad QX200 system. The ddPCR assay has a limit of detection of ≤0.15% variant allele fraction. Baseline characteristics and imaging reports at time of EGFR ctDNA testing were reviewed retrospectively for a 1 year period., Results: The study included 177 patients who had an EGFR ctDNA test. Liver (aOR 3.13) or bone (aOR 2.76) progression or 3-5 sites of progression (aOR 2.22) were predictive of EGFR ctDNA detection. The median OS from first ctDNA test after multiple testing iterations was 12.3 m undetectable EGFR ctDNA, 7.6 m for original EGFR mutation only and 24.1 m with T790M (P=0.001)., Conclusions: Patients with liver or bone progression and 3-5 progressing sites are more likely to have informative EGFR ctDNA testing. Detection of EGFR ctDNA is a negative prognostic indicator in the absence of a T790M resistance mutation, potentially reflecting the disease burden in the absence of targeted therapy options., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-9-581). AP reports personal fees from Bristol-Myers Squibb, Guardant Health, grants from Roche Canada during the conduct of the study. CH reports other from AstraZeneca outside the submitted work. TT reports grants from Astra Zeneca outside the submitted work. JL reports grants from Roche, AstraZeneca, personal fees from Roche, Pfizer, Takeda outside the submitted work. SY reports personal fees from Amgen, Bayer, Novartis, Roche outside the submitted work. CH reports grants from Astra Zeneca during the conduct of the study; grants and personal fees from Astra Zeneca, Eisai, personal fees and other from Boehringer Ingelheim, Roche, personal fees from BMS, Lilly, Merck, Bayer, Novartis outside the submitted work. The other authors have no conflicts of interest to declare., (2020 Translational Lung Cancer Research. All rights reserved.)

Background: Reversal of an international normalized ratio (INR) > 10 with vitamin K is recommended in patients experiencing bleeding; however, information on outcomes with reversal using vitamin K in non-bleeding patients is lacking., Objective: To compare clinical and safety outcomes between non-bleeding patients receiving warfarin with an INR > 10 who did and did not receive a prescription for vitamin K., Patients/methods: This was a retrospective cohort study conducted in an integrated health-care delivery system. Adult patients receiving warfarin therapy who experienced an INR > 10 without bleeding between 01/01/2006 and 06/30/2018 were included. Patients were assessed for an outpatient dispensing or in-office administration of vitamin K on the day of or the day after an INR > 10 and then clinically relevant bleeding, thromboembolism, all-cause mortality, and time to INR < 4 within the next 30 days., Results: A total of 809 patients was included with 332 and 477 who were and were not dispensed vitamin K, respectively. Overall, mean patient age was 71.7 years, 60.1% were female and the mean INR was 10.4 at presentation. There were no differences between groups in 30-day rates of bleeding or thromboembolism (both P > .05). Patients dispensed vitamin K had a higher likelihood of mortality (15.1% versus 10.1%, P = .032, adjusted odds ratio = 1.63, 95% confidence interval 1.03 to 2.57). Overall, time to an INR < 4 was similar between groups., Conclusion: Vitamin K administration was not associated with improved clinical outcomes in asymptomatic patients with an INR > 10., (© 2020 International Society on Thrombosis and Haemostasis.)

This integrative review aimed to identify and synthesize evidence on workplace stress and resilience in the Australian nursing workforce. A search of the published literature was conducted using EMBASE, MEDLINE, CINAHL (EBSCO), PsycINFO, Web of Science, and Scopus. The search was limited to papers published in English from January 2008 to December 2018. The review integrated both qualitative and quantitative data into a single synthesis. Of the 41 papers that met the inclusion criteria, 65.85% (27/41) used quantitative data, 29.26% (12/41) used qualitative data, and 4.87% (2/41) used mixed methods. About 48.78% (20/41) of the papers addressed resilience issues, 46.34% (19/41) addressed workplace stress, and 4.87% (2/41) addressed both workplace stress and resilience. The synthesis indicated that nurses experience moderate to high levels of stress. Several individual attributes and organizational resources are employed by nurses to manage workplace adversity. The individual attributes include the use of work-life balance and organizing work as a mindful strategy, as well as self-reliance, passion and interest, positive thinking, and emotional intelligence as self-efficacy mechanisms. The organizational resources used to build resilience are support services (both formal and informal), leadership, and role modelling. The empirical studies on resilience largely address individual attributes and organizational resources used to build resilience, with relatively few studies focusing on workplace interventions. Our review recommends that research attention be devoted to educational interventions to achieve sustainable improvements in the mental health and wellbeing of nurses., (© 2019 Australian College of Mental Health Nurses Inc.)

Public health authorities recommend young children should not be sedentary for more than one hour at a time. This study assessed the frequency and duration of sedentary bouts in children attending family child care homes (FCCHs); and examined associations with FCCH provider practices related to sedentary behaviors. Overall, 127 children (aged 3.5 ± 1.1 years) from 41 FCCHs participated in the study. Sedentary bouts were measured using an accelerometer worn for the duration of FCCHs attendance over a randomly selected week. Provider practices were assessed using the Nutrition and Physical Activity Self-Assessment for Child Care self-assessment instrument. Children attending FCCHs mostly accumulated short sedentary bouts (<5 min) with very few lasting more than 10 min. Boys exhibited significantly fewer sedentary bouts, and significantly less sedentary time in bouts than girls. Children attending FCCHs that met or exceeded childcare standards for outdoor active play, had portable play equipment, offered a variety of fixed play equipment, and/or adequate indoor play space exhibited significantly fewer sedentary bouts and significantly less sedentary time accumulated in short and medium length bouts. Programs encouraging FCCHs to adopt physical activity promoting practices could potentially reduce child sedentary time while in care.

Background: Individuals with hypertrophic cardiomyopathy (HCM), even when asymptomatic, are at-risk for sudden cardiac death and stroke from arrhythmias, making it imperative to identify individuals affected by this familial disorder. Consensus guidelines recommend that first-degree relatives (FDRs) of a person with HCM undergo serial cardiovascular evaluations., Methods: We determined the uptake of family screening in patients with HCM and developed an online video intervention to facilitate family communication and screening. Family screening and genetic testing data were collected through a prospective quality improvement initiative, a standardized clinical assessment and management plan (SCAMP), utilized in an established cardiovascular genetics clinic. Patients were prescribed an online video if screening of their FDRs was incomplete and a pilot study on video utilization and family communication was conducted., Results: Two-hundred and sixteen probands with HCM were enrolled in SCAMP Phase I and 190 were enrolled in SCAMP Phase II. In both phases, probands reported that 51% of FDRs had been screened (382/749 in Phase I, 258/504 in Phase II). Twenty patients participated in a pilot study on video utilization and family communication. Nine participants reported watching the video and six participants reported sharing the video with relatives; however only one participant reported sharing the video with relatives who were not yet aware of the diagnosis of HCM in the family., Conclusion: Despite care in a specialized cardiovascular genetics clinic, approximately one half of FDRs of patients with HCM remained unscreened. Online interventions and videos may serve as supplemental tools for patients communicating genetic risk information to relatives., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Background: Dietary interventions are implicated in the development of atopic dermatitis, psoriasis, and acne., Objective: To investigate the effect of diet and the bile acid (BA) receptors, such as TGR5 (Takeda G protein receptor 5) and S1PR2 (sphingosine-1-phosphate receptor 2) in the development of dermatitis., Methods: C57BL/6 mice were fed a control diet (CD) or Western diet (WD) since weaning until they were 10 months old followed by analyzing histology, gene expression, and BA profiling., Results: Mice developed dermatitis as they aged and the incidence was higher in females than males. Additionally, WD intake substantially increased the incidence of dermatitis. Cutaneous antimicrobial peptide genesS100A8, S100A9, and Defb4 were reduced in WD-fed mice, but increased when mice developed skin lesions. In addition, Tgr5 and TGR5-regulated Dio2 and Nos3 were reduced in WD intake but induced in dermatitic lesions. Trpa1 and Trpv1, which mediate itch, were also increased in dermatitic lesions. The expression of S1pr2 and genes encoding sphingosine kinases, S1P phosphatases, binding protein, and transporter were all reduced by WD intake but elevated in dermatitic lesions. Furthermore, dermatitis development increased total cutaneous BA with an altered profile, which may change TGR5 and S1PR2 activity. Moreover, supplementation with BA sequestrant cholestyramine reduced epidermal thickening as well as cutaneous inflammatory cytokines., Conclusion: In summary, activation of TGR5 and S1PR2, which regulate itch, keratinocyte proliferation, metabolism, and inflammation, may contribute to WD-exacerbated dermatitis with Th2 and Th17 features. In addition, elevated total BA play a significant role in inducing dermatitis and cutaneous inflammation., (Copyright © 2019 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Background: Shortages of skills needed to deliver optimal health care in rural and remote locations raises questions about using extended scopes of practice or advanced practice models in a range of health professions. The nurse practitioner (NP) model was introduced to address health service gaps; however, its sustainability has been questioned, while other extended scope of practice roles have not progressed in Australia. This study aimed to explore the experiences and perceptions of NPs and their colleagues about barriers to and enablers of extended scope of practice and consider the relevance of the findings to other health professions., Methods: Semi-structured, in-depth interviews were conducted with primary, nurse practitioner informants, who were also invited to nominate up to two colleagues, as secondary informants. Data analysis was guided by a multi-level, socio-institutional lens of macro-, meso- and micro-perspectives., Results: Fifteen primary informants and five colleagues were interviewed from various rural and remote locations. There was a fairly even distribution of informants across primary, aged, chronic and emergency or critical care roles. Key barriers and enablers at each level of analysis were identified. At the macro-level were legal, regulatory, and economic barriers and enablers, as well as job availability. The meso-level concerned local health service and community factors, such as attitudes and support from managers and patients. The micro-level relates to day-to-day practice. Role clarity was of considerable importance, along with embedded professional hierarchies and traditional role expectations influencing interactions with individual colleagues. Given a lack of understanding of NP scope of practice, NPs often had to expend effort promoting and advocating for their roles., Conclusions: For communities to benefit from extended scope of practice models of health service delivery, energy needs to be directed towards addressing legislative and regulatory barriers. To be successful, extended scope of practice roles must be promoted with managers and decision-makers, who may have limited understanding of the clinical importance. Support is also important from other members of the interprofessional health care team., Competing Interests: Ethics approval was from the University Newcastle Human Research Ethics Committee (Protocol Number H-2015-0392, 18 December 2015). All participants gave their informed consent in writing after having been provided with a participant information statement.Prior to giving consent, participants were informed that results of this study may be the subject of journal articles or conference presentations.The authors declare that there are no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Effective clinical practice supervision for health students is essential prior to commencing their respective professions. Students require adequate preparation before their clinical practice event with an experienced clinical supervisor able to impart professional 'know how' and skills to students. The purpose of this study was to describe final year health students' perspectives and experiences of clinical supervision, and to develop an interprofessional model of clinical supervision. Focus groups and semi-structured interviews were conducted with undergraduate health students across a range of disciplines. Some students provided email comments. Qualitative data was analysed thematically using NVivo (V11). Six key themes and their various sub-themes (refer Table 1) were identified: (1) undergraduate learning valued by the CP provider; (2) effective connections (communications) between student, CS, CP provider and university; (3) undergraduate student learning not being valued; (4) ineffective connections; (5) mitigating factors for students; and (6) the impact of increasing student numbers. Undergraduate health student clinical placement requires careful educational preparation, structuring and adequate support for both the student undergoing the practice event and for the clinical supervisor stewarding the undergraduate health professional. A prospective plan to ensure an excellent experience is required (Fig. 1)., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: To review health information exchange (HIE) processes that affect the health of people with intellectual and developmental disabilities (IDD) and to suggest practical tips and strategies for communicating, collaborating, and coordinating in the primary care setting., Sources of Information: The "Primary care of adults with intellectual and developmental disabilities. 2018 Canadian consensus guidelines" literature review and interdisciplinary input., Main Message: Disparities exist between the provision of health care for the general population and that for people with IDD. These disparities are due in part to gaps in HIE. Health information exchange involves documenting, collecting, and disseminating a patient's health information. In exploring ways to improve HIE for people with IDD, the communication skills of the family physician are considered in the context of the triad that includes the patient, his or her caregivers, and the family physician. The framework of the Patient's Medical Home is used in exploring these processes, and various strategies are offered for communicating, collaborating, and coordinating health care that can be implemented by family physicians in order to narrow the gaps in care that exist for people with IDD., Conclusion: Improvements in HIE by communicating, collaborating, and coordinating health care better will improve health outcomes for people with IDD., (Copyright© the College of Family Physicians of Canada.)

Objective: To update the 2011 Canadian guidelines for primary care of adults with intellectual and developmental disabilities (IDD)., Methods: Family physicians and other health professionals experienced in the care of people with IDD reviewed and synthesized recent empirical, ecosystem, expert, and experiential knowledge. A system was developed to grade the strength of recommendations., Recommendations: Adults with IDD are a heterogeneous group of patients and have health conditions and factors affecting their health that can vary in kind, manifestation, severity, or complexity from those of others in the community. They require approaches to care and interventions that are adapted to their needs. These guidelines provide advice regarding standards of care. References to clinical tools and other practical resources are incorporated. The approaches to care that are outlined here can be applied to other groups of patients that have impairments in cognitive, communicative, or other adaptive functioning., Conclusion: As primary care providers, family physicians play a vital role in promoting the health and well-being of adults with IDD. These guidelines can aid their decision making with patients and caregivers., (Copyright© the College of Family Physicians of Canada.)

Objective: To provide primary care physicians with an understanding of the causes of behaviours that challenge (BTC) in adults with intellectual and developmental disabilities (IDD), as presented in the 2018 Canadian consensus guidelines for primary care of adults with IDD; to offer a systematic approach to the assessment and treatment of such behaviours; and to link to tools to support these assessments., Sources of Information: This review elaborates upon guidelines 26 to 29 in the mental health section of the 2018 Canadian consensus guidelines. Several of the authors participated in the development of these guidelines, which were based on literature searches and interdisciplinary input., Main Message: Most adults with IDD are followed by primary care providers but they comprise a small proportion of primary care practices. Unique ways of communicating needs, diagnostic queries, and BTC are common in this population. This complexity can lead to missed diagnoses and inappropriate antipsychotic medication use with attendant risks. This article presents a systematic approach, HELP, to the assessment and treatment of factors of Health, Environment, Lived experience, and Psychiatric conditions that can lead to BTC and includes tools to support these assessments., Conclusion: A structured approach to the assessment and treatment of BTC in adults with IDD helps family physicians provide guideline-directed, individualized care to this population. This includes a systematic evaluation using the HELP framework that takes place over multiple visits. A team of health professionals might be needed for optimal care, but these resources are not routinely available across Canada., (Copyright© the College of Family Physicians of Canada.)

Objectives: To develop an actionable test using fluorescence capillary electrophoresis (FCE) to assess loss of heterozygosity (LOH) of histologically similar low-grade lesions (LGLs) to identify high-risk lesions for oral cancer progression., Study Design: To determine the cutoffs of LOH, the FCE results of 52 surgical margin samples were used to compare with the existing LOH results from the previously validated 32 P-GE approach. Using the developed FCE workflow, an independent set of 102 LGLs with known progression status was used to determine the LOH molecular risk (MR) patterns and associated risk of progression., Results: Using 65% cutoff LOH-FCE, the agreement of LOH- 32 P-GE had an average of 82.3% (76.8-87.8). Compared with nonprogressors (n = 61), anatomic site and MR patterns (LOH at 9 p21, 3 p14, or 17 p13) were independent risk factors. High-risk profile of tongue and MR3 (LOH at 9 p21 and/or 3 p14 and 17 p13) was significantly associated with progression (hazard ratio [HR] 6.7; 95% confidence interval [CI] 2.6-17.6) with specificity of 98.4% at identifying progressors., Conclusions: We have developed an objective test using LOH to stratify the risk of LGLs. With further validation, it can be used in the clinical settings to provide clinicians additional information guiding the management of these lesions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Occupants of aircraft have reported an array of symptoms related to general discomfort and irritation. Volatile organic compounds (VOCs) have been suggested to contribute to the reported symptoms. VOCs are from products used, bioeffluents from people and oxidation reaction products. Thirty-six healthy, young female subjects rated symptoms and environmental quality during an eight-hour exposure to groups of compounds often present in aircraft: (i) long-chain carbonyls, (ii) simulated bioeffluents, and (iii) short-chain carbonyls/organic acids. Statistically more symptoms were identified for the simulated bioeffluents and, to a lesser extent, short-chain carbonyls/organic acids compared to a control condition, although they remained in the acceptable range. There were three temporal patterns in the environmental quality and symptom reports: (i) an adaptive response (immediate increases followed by a decline); (ii) an apparent physiological effect (increases one to three hours into the exposure that remained elevated); and (iii) no statistical differences in reported environmental quality or symptom severity compared to the control air conditions. Typical concentrations found in aircraft can cause transitory symptoms in healthy individuals questioning the adequacy of current standards. Understanding the effects on individuals sensitive to air pollutants and methods to remove the compounds causing the greatest symptom responses are needed., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

As NHS England and the health system makes further investments in the deployment of health information technology (HIT) across NHS sites, this review article considers some of the benefits HIT can provide in secondary care, including the potential of creating innovation ecosystems.

Background: Antibiotic resistance is a major public health problem. Infections caused by multidrug-resistant bacteria are associated with prolonged hospital stay and death compared with infections caused by susceptible bacteria. Appropriate antibiotic use in hospitals should ensure effective treatment of patients with infection and reduce unnecessary prescriptions. We updated this systematic review to evaluate the impact of interventions to improve antibiotic prescribing to hospital inpatients., Objectives: To estimate the effectiveness and safety of interventions to improve antibiotic prescribing to hospital inpatients and to investigate the effect of two intervention functions: restriction and enablement., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library), MEDLINE, and Embase. We searched for additional studies using the bibliographies of included articles and personal files. The last search from which records were evaluated and any studies identified incorporated into the review was January 2015., Selection Criteria: We included randomised controlled trials (RCTs) and non-randomised studies (NRS). We included three non-randomised study designs to measure behavioural and clinical outcomes and analyse variation in the effects: non- randomised trials (NRT), controlled before-after (CBA) studies and interrupted time series (ITS) studies. For this update we also included three additional NRS designs (case control, cohort, and qualitative studies) to identify unintended consequences. Interventions included any professional or structural interventions as defined by the Cochrane Effective Practice and Organisation of Care Group. We defined restriction as 'using rules to reduce the opportunity to engage in the target behaviour (or increase the target behaviour by reducing the opportunity to engage in competing behaviours)'. We defined enablement as 'increasing means/reducing barriers to increase capability or opportunity'. The main comparison was between intervention and no intervention., Data Collection and Analysis: Two review authors extracted data and assessed study risk of bias. We performed meta-analysis and meta-regression of RCTs and meta-regression of ITS studies. We classified behaviour change functions for all interventions in the review, including those studies in the previously published versions. We analysed dichotomous data with a risk difference (RD). We assessed certainty of evidence with GRADE criteria., Main Results: This review includes 221 studies (58 RCTs, and 163 NRS). Most studies were from North America (96) or Europe (87). The remaining studies were from Asia (19), South America (8), Australia (8), and the East Asia (3). Although 62% of RCTs were at a high risk of bias, the results for the main review outcomes were similar when we restricted the analysis to studies at low risk of bias.More hospital inpatients were treated according to antibiotic prescribing policy with the intervention compared with no intervention based on 29 RCTs of predominantly enablement interventions (RD 15%, 95% confidence interval (CI) 14% to 16%; 23,394 participants; high-certainty evidence). This represents an increase from 43% to 58% .There were high levels of heterogeneity of effect size but the direction consistently favoured intervention.The duration of antibiotic treatment decreased by 1.95 days (95% CI 2.22 to 1.67; 14 RCTs; 3318 participants; high-certainty evidence) from 11.0 days. Information from non-randomised studies showed interventions to be associated with improvement in prescribing according to antibiotic policy in routine clinical practice, with 70% of interventions being hospital-wide compared with 31% for RCTs. The risk of death was similar between intervention and control groups (11% in both arms), indicating that antibiotic use can likely be reduced without adversely affecting mortality (RD 0%, 95% CI -1% to 0%; 28 RCTs; 15,827 participants; moderate-certainty evidence). Antibiotic stewardship interventions probably reduce length of stay by 1.12 days (95% CI 0.7 to 1.54 days; 15 RCTs; 3834 participants; moderate-certainty evidence). One RCT and six NRS raised concerns that restrictive interventions may lead to delay in treatment and negative professional culture because of breakdown in communication and trust between infection specialists and clinical teams (low-certainty evidence).Both enablement and restriction were independently associated with increased compliance with antibiotic policies, and enablement enhanced the effect of restrictive interventions (high-certainty evidence). Enabling interventions that included feedback were probably more effective than those that did not (moderate-certainty evidence).There was very low-certainty evidence about the effect of the interventions on reducing Clostridium difficile infections (median -48.6%, interquartile range -80.7% to -19.2%; 7 studies). This was also the case for resistant gram-negative bacteria (median -12.9%, interquartile range -35.3% to 25.2%; 11 studies) and resistant gram-positive bacteria (median -19.3%, interquartile range -50.1% to +23.1%; 9 studies). There was too much variance in microbial outcomes to reliably assess the effect of change in antibiotic use. Heterogeneity of intervention effect on prescribing outcomesWe analysed effect modifiers in 29 RCTs and 91 ITS studies. Enablement and restriction were independently associated with a larger effect size (high-certainty evidence). Feedback was included in 4 (17%) of 23 RCTs and 20 (47%) of 43 ITS studies of enabling interventions and was associated with greater intervention effect. Enablement was included in 13 (45%) of 29 ITS studies with restrictive interventions and enhanced intervention effect., Authors' Conclusions: We found high-certainty evidence that interventions are effective in increasing compliance with antibiotic policy and reducing duration of antibiotic treatment. Lower use of antibiotics probably does not increase mortality and likely reduces length of stay. Additional trials comparing antibiotic stewardship with no intervention are unlikely to change our conclusions. Enablement consistently increased the effect of interventions, including those with a restrictive component. Although feedback further increased intervention effect, it was used in only a minority of enabling interventions. Interventions were successful in safely reducing unnecessary antibiotic use in hospitals, despite the fact that the majority did not use the most effective behaviour change techniques. Consequently, effective dissemination of our findings could have considerable health service and policy impact. Future research should instead focus on targeting treatment and assessing other measures of patient safety, assess different stewardship interventions, and explore the barriers and facilitators to implementation. More research is required on unintended consequences of restrictive interventions.

We describe a novel droplet digital PCR (ddPCR) assay capable of detecting genomic alterations associated with inversion translocations. It is applied here to detection of rearrangements in the anaplastic lymphoma kinase (ALK) gene associated with ALK-positive non-small-cell lung cancer (NSCLC). NSCLC patients may carry a nonreciprocal translocation on human chromosome 2, in which synchronized double stranded breaks (DSB) within the echinoderm microtubule-associated protein-like 4 (EML4) gene and ALK lead to an inversion of genetic material that forms the non-natural gene fusion EML4-ALK encoding a constitutively active tyrosine kinase that is associated with 3 to 7% of all NSCLCs. Detection of ALK rearrangements is currently achieved in clinics through direct visualization via a fluorescent in situ hybridization (FISH) assay, which can detect those rearrangements to a limit of detection (LOD) of ca. 15%. We show that the ddPCR assay presented here provides a LOD of 0.25% at lower cost and with faster turnaround times.

The objective of this study was to explore factors affecting decisions to adopt new technologies into dental practice using a colorimetric rinse test for detection of periodontal disease as a model. Focus groups with key informants in Canadian dentistry and dental hygiene were conducted. A deductive approach used Rogers's diffusion of innovation theory as a framework for organizing codes and subcodes. Two members of the research team independently reviewed and analyzed the data using NVivo 10. The attributes of the technology itself emerged as primary influencers. Perceived relative advantages of the diagnostic mouth rinse over existing methods were potential time efficiency, low implementation cost, and utility of the tool. Low complexity, compatibility with existing routines/beliefs, and the potential for reinvention-the use of a technology for other than its intended purpose (i.e., patient education, monitoring of disease, screening tool in nondental settings)-were other important features enhancing adoption. An overarching concern was that any new technology benefit the patient. Contextual factors also play a role. Numerous communication channels, including opinion leaders, patients, marketing, continuing education courses, and strength of evidence, influenced clinicians, with peer interaction being a stronger influence than marketing. Similar themes arose from specialist, general dentist, and dental hygienist focus groups. Adopter characteristics also came into play: participants ranged in their self-reported innovativeness with many considering themselves "early adopters" of new technology. Findings of this study suggest that the innovation adoption process is not straightforward, but attributes of the innovation, contextual factors, and adopter characteristics play important roles in the process. Knowledge Transfer Statement: Various factors affect the adoption of new tools into clinical dental practice. These include attributes of the test or tool itself, the context of the settings in which the tool is introduced to practitioners, and the characteristics of the clinicians themselves. A qualitative study of dentists and dental hygienists investigated these factors. Situations in which dentists and hygienists interact with their peers and colleagues-through social networks, continuing education courses, conventions, or personal contact-were a major driver in the decision to adopt new technologies. However, even among "early adopters," most were reluctant to use new tests or tools unless they perceived a benefit to their patients or practice.

The analysis of shape is a key part of anatomical research and in the large majority of cases landmarks provide a standard starting point. However, while the technology of image capture has developed rapidly and in particular three-dimensional imaging is widely available, the definitions of anatomical landmarks remain rooted in their two-dimensional origins. In the important case of the human face, standard definitions often require careful orientation of the subject. This paper considers the definitions of facial landmarks from an interdisciplinary perspective, including biological and clinical motivations, issues associated with imaging and subsequent analysis, and the mathematical definition of surface shape using differential geometry. This last perspective provides a route to definitions of landmarks based on surface curvature, often making use of ridge and valley curves, which is genuinely three-dimensional and is independent of orientation. Specific definitions based on curvature are proposed. These are evaluated, along with traditional definitions, in a study that uses a hierarchical (random effects) model to estimate the error variation that is present at several different levels within the image capture process. The estimates of variation at these different levels are of interest in their own right but, in addition, evidence is provided that variation is reduced at the observer level when the new landmark definitions are used., (© 2015 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

A need exists for robust and cost-effective assays to detect a single or small set of actionable point mutations, or a complete set of clinically informative mutant alleles. Knowledge of these mutations can be used to alert the clinician to a rare mutation that might necessitate more aggressive clinical monitoring or a personalized course of treatment. An example is BRAF, a (proto)oncogene susceptible to either common or rare mutations in codon V600 and adjacent codons. We report a diagnostic technology that leverages the unique capabilities of droplet digital PCR to achieve not only accurate and sensitive detection of BRAF(V600E) but also all known somatic point mutations within the BRAF V600 codon. The simple and inexpensive two-well droplet digital PCR assay uses a chimeric locked nucleic acid/DNA probe against wild-type BRAF and a novel wild-type-negative screening paradigm. The assay shows complete diagnostic accuracy when applied to formalin-fixed, paraffin-embedded tumor specimens from metastatic colorectal cancer patients deficient for Mut L homologue-1., (Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Formed from a reciprocal translocation t(9:22)(q34;q11) of genetic material between the long arms of human chromosomes 9 and 22, the constitutively active breakpoint cluster region (BCR) Abelson 1 (ABL) tyrosine kinase BCR-ABL is known to be causative of chronic myelogenous leukemia (CML). In 98% of CML patients harboring the t(9:22)(q34;q11) translocation, known as the Philadelphia chromosome, the chimeric BCR-ABL oncogene is created through cleavage of the BCR gene within its major breakpoint region (M-BCR) and breakage of the ABL gene within a 100-kbp region downstream of exon 2a. Clinical detection of the fused BCR-ABL oncogene currently relies on direct visualization by fluorescence in situ hybridization (FISH), a relatively tedious assay that typically offers a detection limit of ca. 2%. Here, we describe a novel assay that uses droplet digital PCR (ddPCR) technology to reliably measure M-BCR status and the presence of BCR-ABL. When applied to cell-line models of CML, the assay accurately quantifies BCR-ABL frequency to a detection limit of 0.25%. It therefore offers improved specificity relative to FISH, and may allow identification of variant translocation patterns, including derivative chromosome 9 deletions.

Background: Epidemiological studies indicate that disruption of circadian rhythm by shift work increases the risk of breast and prostate cancer. Our studies demonstrated that carcinogens disrupt the circadian expression of circadian genes (CGs) and circadian-controlled genes (CCGs) during the early stages of rat mammary carcinogenesis. A chemopreventive regimen of methylselenocysteine (MSC) restored the circadian expression of CGs and CCGs, including PERIOD 2 (PER2) and estrogen receptor β (ERS2), to normal. The present study evaluated whether changes in CG and CCG expression in whole blood can serve as indicators of circadian disruption in shift workers., Methods: Fifteen shift workers were recruited to a crossover study. Blood samples were drawn before (6 PM) and after (8 AM) completing a night shift after at least seven days on floating night-shift rotation, and before (8 AM), during (1 PM), and after (6 PM) completing seven days on day shift. The plasma melatonin level and messenger RNA (mRNA) expression of PER2, nuclear receptor subfamily 1, group d, member 1 (NR1D1), and ERS2 were measured, and the changes in levels of melatonin and gene expression were evaluated with statistical analyses., Results: The mRNA expression of PER2 was affected by shift (p = 0.0079); the levels were higher in the evening for the night shift, but higher in the morning for the day shift. Increased PER2 expression (p = 0.034) was observed in the evening on the night versus day shifts. The melatonin level was higher in the morning for both day shifts (p = 0.013) and night shifts (p <0.0001)., Conclusion: Changes in the level of PER2 gene expression can serve as a biomarker of disrupted circadian rhythm in blood cells. Therefore, they can be a useful intermediate indicator of efficacy in future MSC-mediated chemoprevention studies., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The biological effects of atrial natriuretic peptide (ANP) are mediated by natriuretic peptide receptors (NPRs), which can either activate guanylyl cyclase (NPRA and NPRB) or inhibit adenylyl cyclase (NPRC) to modulate intracellular cGMP or cAMP, respectively. During cardiac development, ANP serves as an early maker of differentiating atrial and ventricular chamber myocardium. As development proceeds, expression of ANP persists in the atria but declines in the ventricles. Currently, it is not known whether ANP is secreted or the ANP-NPR signaling system plays any active role in the developing ventricles. Thus the primary aims of this study were to 1) examine biological activity of ANP signaling systems in embryonic ventricular myocardium, and 2) determine whether ANP signaling modulates proliferation/differentiation of undifferentiated cardiac progenitor cells (CPCs) and/or cardiomyocytes. Here, we provide evidence that ANP synthesized in embryonic day (E)11.5 ventricular myocytes is actively secreted and processed to its biologically active form. Notably, NPRA and NPRC were detected in E11.5 ventricles and exogenous ANP stimulated production of cGMP in ventricular cell cultures. Furthermore, we showed that exogenous ANP significantly decreased cell number and DNA synthesis of CPCs but not cardiomyocytes and this effect could be reversed by pretreatment with the NPRA receptor-specific inhibitor A71915. ANP treatment also led to a robust increase in nuclear p27 levels in CPCs compared with cardiomyocytes. Collectively, these data provide evidence that in the developing mammalian ventricles ANP plays a local paracrine role in regulating the balance between CPC proliferation and differentiation via NPRA/cGMP-mediated signaling pathways., (Copyright © 2015 the American Physiological Society.)

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu., (Copyright © 2015 Leung et al.)

Rationale and Aim: While interprofessional practice has been promoted as a solution to the challenges besetting rural health services, current evidence does not offer a clear explanation as to why it is effective in some domains and yet is not successful in others. At the same time, rural clinicians are frequently faced with major workforce pressures and this has a significant influence on professional practice. The aim of this study was to explore how these pressures impact on rural interprofessional practice., Method: This study is part of a larger project investigating factors that enhance and detract from effective interprofessional working. We utilised a modified realistic evaluation approach to analyse the context, mechanisms and outcomes of rural interprofessional practice. Approval for this study was granted by an accredited research ethics committee. Semi-structured interviews were conducted with 22 rural clinicians who were purposively recruited from a range of settings, roles, locations and professions., Findings and Discussion: We found that clinicians often invested in interprofessional practice because of the need to manage intense workloads and this necessitated sharing of responsibilities across disciplines and blurring of role boundaries. Paradoxically, participants noted that workload pressures hampered interprofessional working if there were long-term skill shortages. Sharing workload and responsibility is an important motivator for rural practitioners to engage in interprofessional practice; however, this driver is only effective under circumstances where there are sufficient resources to facilitate collaboration. In the context of intransient resource challenges, rural health service managers would be best to focus on enabling IPP through facilitating role understanding and respect between clinicians. This is most feasible via informal workplace learning and allowing time for teams to reflect on collaborative processes., (© 2014 Nordic College of Caring Science.)

Background: Optimal mouth care is integral to the health and quality of life of dependent older adults.Yet, a persistent lack of adequate oral care in long-term care (LTC) facilities exacerbates the burden of disease experienced by residents. The reasons for this are complex and create enormous challenges for care providers, clinicians, and administrators dedicated to comprehensive high quality care., Objective: The aim of this study was to develop, implement, and evaluate a comprehensive program for daily mouth care for LTC., Design: A case study design using a participatory and qualitative approach examined how individual, organizational (workplace practices and culture), and system factors (standards and policy) influenced the development and implementation of a comprehensive program to improve the delivery of daily oral care in LTC., Setting and Participants: The research was undertaken in 3 LTC residences administered under the same health authority and included personal care providers, nurse managers, and directors of care., Intervention: A comprehensive program for care providers including, education, resources, and organizational guidelines, to improve the delivery of daily mouth care to LTC residents was created, rolled out, and refined over a 12-month period., Measurements: Data was collected through diary studies, targeted interviews, field notes, oral care activities records, site team meetings, and direct feedback from members of the care team., Results: The oral care intervention resulted in a heightened awareness, support and greater efficiency amongst care team. The presence of a "champion" was a key feature for sustaining processes. Management had a clear role to play to ensure support and accountability for the intervention., Conclusions: Optimizing oral care in long-term care can be achieved through an integrated approach that includes education, provision of resources, an oral care champion, support from managers and administrators, and appropriate organizational policy., (Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: For many individuals, daily commuting activities on roadways account for a substantial proportion of total exposure, as well as peak-level exposures, to traffic-related air pollutants (TRAPS) including ultrafine particles, but the health impacts of these exposures are not well-understood. We sought to determine if exposure to TRAPs particles during commuting causes acute oxidative stress in the respiratory tract or changes in heart rate variability (HRV), a measure of autonomic activity., Methods: We conducted a randomized, cross-over trial in which twenty-one young adults took two 1.5-hr rides in a passenger vehicle in morning rush-hour traffic. The subjects wore a powered-air-purifying respirator, and were blinded to high-efficiency particulate air (HEPA) filtration during one of the rides. At time points before and after the rides, we measured HRV and markers of oxidative stress in exhaled breath condensate (EBC) including nitrite, the sum of nitrite and nitrate, malondialdehyde, and 8-isoprostane. We used mixed linear models to evaluate the effect of exposure on EBC and HRV outcomes, adjusting for pre-exposure response levels. We used linear models to examine the effects of particle concentrations on EBC outcomes at post-exposure time points., Results: Mean EBC nitrite and the sum of nitrite and nitrate were increased from baseline at immediately post-exposure comparing unfiltered to filtered rides (2.11 μM vs 1.70 μM, p = 0.02 and 19.1 μM vs 10.0 μM, p = 0.02, respectively). Mean EBC malondialdehyde (MDA) concentrations were about 10% greater following the unfiltered vs. filtered exposures, although this result was not statistically significant. We found no significant associations between exposure to traffic particles and HRV outcomes at any of the time points. At immediately post-exposure, an interquartile range increase in particle number concentration was associated with statistically significant increases in nitrite (99.4%, 95% CI 32.1% to 166.7%) and nitrite + nitrate (75.7%, 95% CI 21.5% to 130.0%)., Conclusions: Increases in markers of oxidative stress in EBC may represent early biological responses to widespread exposures to TRAPs particles that affect passengers in vehicles on heavily trafficked roadways.

Background: Insulin-like growth factors (IGF-I and IGF-II) signal via the type 1 IGF receptor (IGF-1R) and IGF-II also activates the insulin receptor isoform A (IR-A). Signalling via both receptors promotes tumour growth, survival and metastasis. In some instances IGF-II action via the IR-A also promotes resistance to anti-IGF-1R inhibitors. This study assessed the efficacy of two novel modified IGF-binding protein-2 (IGFBP-2) proteins that were designed to sequester both IGFs. The two modified IGFBP-2 proteins were either protease resistant alone or also lacked the ability to bind extracellular matrix (ECM)., Methods: The modified IGFBP-2 proteins were tested in vitro for their abilities to inhibit cancer cell proliferation and in vivo to inhibit MCF-7 breast tumour xenograft growth., Results: Both mutants retained low nanomolar affinity for IGF-I and IGF-II (0.8-2.1-fold lower than IGFBP-2) and inhibited cancer cell proliferation in vitro. However, the combined protease resistant, non-matrix-binding mutant was more effective in inhibiting MCF-7 tumour xenograft growth and led to inhibition of angiogenesis., Conclusions: By removing protease cleavage and matrix-binding sites, modified IGFBP-2 was effective in inhibiting tumour growth and reducing tumour angiogenesis.

Objective: To determine barriers and facilitators associated with the acceptance of a new diagnostic screening tool for periodontitis., Methods: As part of a larger study to examine factors that affect the adoption of new technology by dentists, we piloted an online survey of Canadian dentists through an electronic newsletter produced by the Journal of the Canadian Dental Association. A new oral rinse that screens for the presence of periodontitis by estimating neutrophil abundance in saliva was used for illustrative purposes. The survey included questions about the types of patients for which the test would be beneficial, how the test might be incorporated into practice and how much the dentist would be willing to pay for the test., Results: As the survey was delivered through a new communication tool, the response rate was low. Nonetheless there appeared to be interest in new periodontal screening tools to complement existing diagnostic tests for periodontitis. The test was seen as a valuable educational tool for patients; however, the cost to administer the test was determined to be an issue., Conclusions: Despite the low response rate, dentists were interested in new screening tests for periodontitis. A larger study with a more representative sample could provide valuable information for scientists who are interested in taking their research from the bench to chairside.

Background: Although interprofessional practice (IPP) offers the potential to enhance rural health services and provide support to rural clinicians, IPP may itself be problematic due to workforce limitations and service fragmentation. Differing socioeconomic and geographic characteristics of rural communities means that the way that IPP occurs in rural contexts will necessarily differ from that occurring in metropolitan contexts. The aim of this study was to investigate the factors contributing to effective IPP in rural contexts, to examine how IPP happens and to identify barriers and enablers., Methods: Using Realistic Evaluation as a framework, semi-structured interviews were conducted with health professionals in a range of rural healthcare contexts in NSW, Australia. Independent thematic analysis was undertaken by individual research team members, which was then integrated through consensus to achieve a qualitative description of rural IPP practice., Results: There was clear evidence of diversity and complexity associated with IPP in the rural settings that was supported by descriptions of collaborative integrated practice. There were instances where IPP doesn't and could happen. There were a number of characteristics identified that significantly impacted on IPP including the presence of a shared philosophical position and valuing of IPP and recognition of the benefits, funding to support IPP, pivotal roles, proximity and workforce resources., Conclusions: The nature of IPP in rural contexts is diverse and determined by a number of critical factors. This study goes some of the way towards unravelling the complexity of IPP in rural contexts, highlighting the strong motivating factors that drive IPP. However, it has also identified significant structural and relational barriers related to workload, workforce, entrenched hierarchies and ways of working and service fragmentation. Further research is required to explicate the mechanisms that drive successful IPP across a range of diverse rural contexts in order to inform the implementation of robust flexible strategies that will support sustainable models of rural IPP.

Objective: The structural basis of normoalbuminuric renal insufficiency in patients with type 2 diabetes remains to be elucidated. We compared renal biopsy findings in patients with type 2 diabetes and estimated glomerular filtration rate (eGFR) and measured GFR of <60 mL/min/1.73 m2, associated with either normo-, micro-, or macroalbuminuria., Research Design and Methods: In patients with normo- (n = 8) or microalbuminuria (n = 6), renal biopsies were performed according to a research protocol. In patients with macroalbuminuria (n = 17), biopsies were performed according to clinical indication. Findings were categorized according to the Fioretto classification: category 1 (C1), normal/near normal; category 2 (C2), typical diabetic nephropathy (DN) with predominantly glomerular changes; and category 3 (C3), atypical with disproportionately severe interstitial/tubular/vascular damage and with no/mild diabetic glomerular changes., Results: In our study population (mean eGFR 35 mL/min/1.73 m2), typical glomerular changes (C2) of DN were observed in 22 of 23 subjects with micro- or macroalbuminuria compared with 3 of 8 subjects with normoalbuminuria (P = 0.002). By contrast, predominantly interstitial or vascular changes (C3) were seen in only 1 of 23 subjects with micro- or macroalbuminuria compared with 3 of 8 normoalbuminuric subjects (P = 0.08). Mesangial area increased progressively from normal controls to patients with type 2 diabetes and normo-, micro-, and macroalbuminuria. Varying degrees of arteriosclerosis, although not necessarily the predominant pattern, were seen in seven of eight subjects with normoalbuminuria., Conclusions: Typical renal structural changes of DN were observed in patients with type 2 diabetes and elevated albuminuria. By contrast, in normoalbuminuric renal insufficiency, these changes were seen less frequently, likely reflecting greater contributions from aging, hypertension, and arteriosclerosis.

Aim: To describe the research protocol that will be used to investigate factors contributing to effective interprofessional practice in a rural context in Australia., Background: Interprofessional practice is a key strategy for overcoming rural health challenges; however, our knowledge of interprofessional initiatives and consequences in rural areas is limited., Design: A modified realistic evaluation approach will be used to explore the structures, systems, and social processes contributing to effective interprofessional outcomes. This 'context-mechanism-outcome' approach provides a useful framework for identifying why and how interprofessional practice works in rural contexts., Method: Initial propositions regarding the factors that explain effective collaborative practice will be generated through interviews with lead clinicians, policy-makers, and clinician managers. Clinician interviews, document analysis, and multi-participant focus groups will be used as evidence to support, refine, or redevelop the initial propositions. This will allow the development of a model of rural interprofessional practice that will explain how and why collaborative approaches work in rural environments. This study is funded by an Institute of Rural Clinical Services and Teaching grant (January 2010)., Discussion: Rural healthcare challenges are well documented; however, studies investigating the nature of interprofessional practice in rural contexts are not common. Rural contexts also present research design, particularly data collection, challenges. This proposed research is one of the first to identify the factors that facilitate or constrain effective interprofessional work in rural settings. This is particularly important, given the continuing workforce shortages and maldistribution and poorer health outcomes in rural communities globally., (© 2013 Blackwell Publishing Ltd.)