In Vivo Imaging Reveals Distinct Inflammatory Activity of CNS Microglia versus PNS Macrophages in a Mouse Model for ALS

Mutations in the enzyme superoxide dismutase-1 (SOD1) cause hereditary variants of the fatal motor neuronal disease Amyotrophic lateral sclerosis (ALS). Pathophysiology of the disease is non-cell-autonomous: neurotoxicity is derived not only from mutant motor neurons but also from mutant neighbouring non-neuronal cells. In vivo imaging by two-photon laser-scanning microscopy was used to compare the role of microglia/macrophage-related neuroinflammation in the CNS and PNS using ALS-linked transgenic SOD1G93A mice. These mice contained labeled projection neurons and labeled microglia/macrophages. In the affected lateral spinal cord (in contrast to non-affected dorsal columns), different phases of microglia-mediated inflammation were observed: highly reactive microglial cells in preclinical stages (in 60-day-old mice the reaction to axonal transection was ∼180% of control) and morphologically transformed microglia that have lost their function of tissue surveillance and injury-directed response in clinical stages (reaction to axonal transection was lower than 50% of control). Furthermore, unlike CNS microglia, macrophages of the PNS lack any substantial morphological reaction while preclinical degeneration of peripheral motor axons and neuromuscular junctions was observed. We present in vivo evidence for a different inflammatory activity of microglia and macrophages: an aberrant neuroinflammatory response of microglia in the CNS and an apparently mainly neurodegenerative process in the PNS

Design programmes to maximise participant engagement: a predictive study of programme and participant characteristics associated with engagement in paediatric weight management.

BACKGROUND: Approximately 50% of paediatric weight management (WM) programme attendees do not complete their respective programmes. High attrition rates compromise both programme effectiveness and cost-efficiency. Past research has examined pre-intervention participant characteristics associated with programme (non-)completion, however study samples are often small and not representative of multiple demographics. Moreover, the association between programme characteristics and participant engagement is not well known. This study examined participant and programme characteristics associated with engagement in a large, government funded, paediatric WM programme. Engagement was defined as the family's level of participation in the WM programme. METHODS: Secondary data analysis of 2948 participants (Age: 10.44 ± 2.80 years, BMI: 25.99 ± 5.79 kg/m(2), Standardised BMI [BMI SDS]: 2.48 ± 0.87 units, White Ethnicity: 70.52%) was undertaken. Participants attended a MoreLife programme (nationwide WM provider) between 2009 and 2014. Participants were classified into one of five engagement groups: Initiators, Late Dropouts, Low- or High- Sporadic Attenders, or Completers. Five binary multivariable logistic regression models were performed to identify participant (n = 11) and programmatic (n = 6) characteristics associated with an engagement group. Programme completion was classified as ≥70% attendance. RESULTS: Programme characteristics were stronger predictors of programme engagement than participant characteristics; particularly small group size, winter/autumn delivery periods and earlier programme years (proxy for scalability). Conversely, participant characteristics were weak predictors of programme engagement. Predictors varied between engagement groups (e.g. Completers, Initiators, Sporadic Attenders). 47.1% of participants completed the MoreLife programme (mean attendance: 59.4 ± 26.7%, mean BMI SDS change: -0.15 ± 0.22 units), and 21% of those who signed onto the programme did not attend a session. CONCLUSIONS: As WM services scale up, the efficacy and fidelity of programmes may be reduced due to increased demand and lower financial resource. Further, limiting WM programme groups to no more than 20 participants could result in greater engagement. Baseline participant characteristics are poor and inconsistent predictors of programme engagement. Thus, future research should evaluate participant motives, expectations, and barriers to attending a WM programme to enhance our understanding of participant WM engagement. Finally, we suggest that session-by-session attendance is recorded as a minimum requirement to improve reporting transparency and enhance external validity of study findings

Situational awareness within objective structured clinical examination stations in undergraduate medical training - a literature search

Background: Medical students may not be able to identify the essential elements of situational awareness (SA) necessary for clinical reasoning. Recent studies suggest that students have little insight into cognitive processing and SA in clinical scenarios. Objective Structured Clinical Examinations (OSCEs) could be used to assess certain elements of situational awareness. The purpose of this paper is to review the literature with a view to identifying whether levels of SA based on Endsley's model can be assessed utilising OSCEs during undergraduate medical training. Methods: A systematic search was performed pertaining to SA and OSCEs, to identify studies published between January 1975 (first paper describing an OSCE) and February 2017, in peer reviewed international journals published in English. PUBMED, EMBASE, PsycINFO Ovid and SCOPUS were searched for papers that described the assessment of SA using OSCEs among undergraduate medical students. Key search terms included "objective structured clinical examination", "objective structured clinical assessment" or "OSCE" and "non-technical skills", "sense-making", "clinical reasoning", "perception", "comprehension", "projection", "situation awareness", "situational awareness" and "situation assessment". Boolean operators (AND, OR) were used as conjunctions to narrow the search strategy, resulting in the limitation of papers relevant to the research interest. Areas of interest were elements of SA that can be assessed by these examinations. Results: The initial search of the literature retrieved 1127 publications. Upon removal of duplicates and papers relating to nursing, paramedical disciplines, pharmacy and veterinary education by title, abstract or full text, 11 articles were eligible for inclusion as related to the assessment of elements of SA in undergraduate medical students. Discussion: Review of the literature suggests that whole-task OSCEs enable the evaluation of SA associated with clinical reasoning skills. If they address the levels of SA, these OSCEs can provide supportive feedback and strengthen educational measures associated with higher diagnostic accuracy and reasoning abilities. Conclusion: Based on the findings, the early exposure of medical students to SA is recommended, utilising OSCEs to evaluate and facilitate SA in dynamic environment

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

New Polynomial-Based Molecular Descriptors with Low Degeneracy

In this paper, we introduce a novel graph polynomial called the ‘information polynomial’ of a graph. This graph polynomial can be derived by using a probability distribution of the vertex set. By using the zeros of the obtained polynomial, we additionally define some novel spectral descriptors. Compared with those based on computing the ordinary characteristic polynomial of a graph, we perform a numerical study using real chemical databases. We obtain that the novel descriptors do have a high discrimination power

A randomized controlled trial to prevent glycemic relapse in longitudinal diabetes care: Study protocol (NCT00362193)

BACKGROUND: Diabetes is a common disease with self-management a key aspect of care. Large prospective trials have shown that maintaining glycated hemoglobin less than 7% greatly reduces complications but translating this level of control into everyday clinical practice can be difficult. Intensive improvement programs are successful in attaining control in patients with type 2 diabetes, however, many patients experience glycemic relapse once returned to routine care. This early relapse is, in part, due to decreased adherence in self-management behaviors. OBJECTIVE: This paper describes the design of the Glycemic Relapse Prevention study. The purpose of this study is to determine the optimal frequency of maintenance intervention needed to prevent glycemic relapse. The primary endpoint is glycemic relapse, which is defined as glycated hemoglobin greater than 8% and an increase of 1% from baseline. METHODS: The intervention consists of telephonic contact by a nurse practitioner with a referral to a dietitian if indicated. This intervention was designed to provide early identification of self-care problems, understanding the rationale behind the self-care lapse and problem solve to find a negotiated solution. A total of 164 patients were randomized to routine care (least intensive), routine care with phone contact every three months (moderate intensity) or routine care with phone contact every month (most intensive). CONCLUSION: The baseline patient characteristics are similar across the treatment arms. Intervention fidelity analysis showed excellent reproducibility. This study will provide insight into the important but poorly understood area of glycemic relapse prevention

Factors contributing to attrition behavior in diabetes self-management programs: A mixed method approach

<p>Abstract</p> <p>Background</p> <p>Diabetes self-management education is a critical component in diabetes care. Despite worldwide efforts to develop efficacious DSME programs, high attrition rates are often reported in clinical practice. The objective of this study was to examine factors that may contribute to attrition behavior in diabetes self-management programs.</p> <p>Methods</p> <p>We conducted telephone interviews with individuals who had Type 2 diabetes (n = 267) and attended a diabetes education centre. Multivariable logistic regression was performed to identify factors associated with attrition behavior. Forty-four percent of participants (n = 118) withdrew prematurely from the program and were asked an open-ended question regarding their discontinuation of services. We used content analysis to code and generate themes, which were then organized under the Behavioral Model of Health Service Utilization.</p> <p>Results</p> <p>Working full and part-time, being over 65 years of age, having a regular primary care physician or fewer diabetes symptoms were contributing factors to attrition behaviour in our multivariable logistic regression. The most common reasons given by participants for attrition from the program were conflict between their work schedules and the centre's hours of operation, patients' confidence in their own knowledge and ability when managing their diabetes, apathy towards diabetes education, distance to the centre, forgetfulness, regular physician consultation, low perceived seriousness of diabetes, and lack of familiarity with the centre and its services. There was considerable overlap between our quantitative and qualitative results.</p> <p>Conclusion</p> <p>Reducing attrition behaviour requires a range of strategies targeted towards delivering convenient and accessible services, familiarizing individuals with these services, increasing communication between centres and their patients, and creating better partnerships between centres and primary care physicians.</p

Understanding missed opportunities for more timely diagnosis of cancer in symptomatic patients after presentation.

The diagnosis of cancer is a complex, multi-step process. In this paper, we highlight factors involved in missed opportunities to diagnose cancer more promptly in symptomatic patients and discuss responsible mechanisms and potential strategies to shorten intervals from presentation to diagnosis. Missed opportunities are instances in which post-hoc judgement indicates that alternative decisions or actions could have led to more timely diagnosis. They can occur in any of the three phases of the diagnostic process (initial diagnostic assessment; diagnostic test performance and interpretation; and diagnostic follow-up and coordination) and can involve patient, doctor/care team, and health-care system factors, often in combination. In this perspective article, we consider epidemiological 'signals' suggestive of missed opportunities and draw on evidence from retrospective case reviews of cancer patient cohorts to summarise factors that contribute to missed opportunities. Multi-disciplinary research targeting such factors is important to shorten diagnostic intervals post presentation. Insights from the fields of organisational and cognitive psychology, human factors science and informatics can be extremely valuable in this emerging research agenda. We provide a conceptual foundation for the development of future interventions to minimise the occurrence of missed opportunities in cancer diagnosis, enriching current approaches that chiefly focus on clinical decision support or on widening access to investigations.We acknowledge the helpful and incisive comments by Dr Rikke Sand Andersen (Aarhus University, Denmark) in conceptualising this piece and in drafts of the manuscript. The work is independent research supported by different funding schemes. GL was supported by a Post-Doctoral Fellowship by the National Institute for Health Research (PDF-2011-04-047) until the end of 2014 and by a Cancer Research UK Clinician Scientist Fellowship award (A18180) from 2015. HS is supported by the VA Health Services Research and Development Service (CRE 12-033; Presidential Early Career Award for Scientists and Engineers USA 14-274), the VA National Center for Patient Safety, the Agency for Health Care Research and Quality (R01HS022087) and in part by the Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (CIN 13–413). PV was supported by CaP, funded by The Danish Cancer Society and the Novo Nordisk Foundation.This is the final version of the article. It first appeared at http://dx.doi.org/10.1038/bjc.2015.4

The Interaction Between Pubertal Timing and Peer Popularity for Boys and Girls: An Integration of Biological and Interpersonal Perspectives on Adolescent Depression

The transition to adolescence marks a time of sharply increased vulnerability to the development of depression, particularly among girls. Past research has examined isolated risk factors from individual theoretical models (e.g., biological, interpersonal, and cognitive) of depression, but few have examined integrative models. This study investigated the conjoint effects of early pubertal timing and popularity in the longitudinal prediction of depressive symptoms. A total of 319 girls and 294 boys (ages 11–14) provided information on their pubertal status, depressive symptoms, and the social status (i.e., popularity) of their peers. Adolescents completed a second measure of depressive symptoms 11 months after the initial time point. Findings supported an integrated biological-interpersonal model in explaining the development of depressive symptoms during adolescence. Early pubertal development was associated with increase in depressive symptoms only when accompanied by low levels of popularity. High levels of popularity buffered the association between early pubertal development and later depressive symptoms. Unexpectedly, these results were significant both for girls and boys. Results are discussed in terms of dynamic systems theories