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Numerous tectonic scenarios have been proposed for terrane growth and accretion within the Archean Dharwar Craton, southern Peninsular India. Previously accepted interpretations involving a two-terrane model—comprising a Western Dharwar Craton (WDC) and Eastern Dharwar Craton (EDC) block—have invoked west-dipping subduction and ocean closure, leading to arc magmatism and accretionary orogeny in the WDC, followed by metamorphic overprinting and collisional orogeny in the EDC. However, recent field investigations have revealed the existence of a previously unrecognized 'central' block (Central Dharwar Craton; CDC) within the craton, which requires revision of this model and reinterpretation of metamorphic and magmatic age data. Five samples of high-pressure, upper amphibolite- and granulite-facies meta-igneous and metasedimentary rocks from the southern portion of the Chitradurga Suture Zone, which divides the WDC and CDC, record minimum peak metamorphic conditions of ∼820–875°C at ∼10 kbar, indicating equilibration at the base of thickened continental crust. U–Pb zircon and Pb–Pb monazite geochronology indicates crystallization of parent mafic magmas at c. 2·61–2·51 Ga and subsequent regional metamorphism of these intrusions to garnet-amphibolite and garnet-granulite facies at c. 2·48–2·44 Ga, bracketing the timing of microblock accretion to the Archean–Proterozoic boundary. Light rare earth element enrichment within these zircon grains indicates magma generation in a suprasubduction-zone environment. In addition, detrital magmatic zircon grains with ages of c. 3·10–3·03 Ga and c. 2·97–2·86 Ga imply contamination of these magmas with Mesoarchean material sourced from the Western Dharwar Craton continental nucleus. Comparison of these metamorphic and magmatic age data with those recorded in the EDC shows that westward-directed subduction is implausible, and that all three terranes (the WDC, CDC, and EDC) must have accreted synchronously, driven by two separate eastward-dipping ocean–continent convergent plate margins. These data further support a recent abundance of observations from the geological record supporting the hypothesis that subduction-driven plate tectonics had initiated on Earth before c. 2·5 Ga, as opposed to a Neoproterozoic onset (c. 0·8–0·9 Ga) reported by numerous studies. [ABSTRACT FROM AUTHOR]

One in seven American adults takes medication to alter or to prevent unwanted experience or behavior. But, the prescription and use of psychiatric medication raises practically important theological and ethical questions for practitioners, for clergy, for scholars, and for people who take medication. How does the prescription and use of psychiatric medication shape imagination and belief about what it means to be human and about the relationship of the body to the acting person? To what extent does medication facilitate technological interpretation and engagement of human life and experience? How does medication use reflect and form modern individualism? How does medication affect human experiences and perceptions of God and of God's action? In this special issue of Christian Bioethics, five scholars from different disciplines—Jeffrey Bishop, M. Therese Lysaught, Warren Kinghorn, Susan Eastman, and John Swinton—engage the meaning of psychiatric medication for Christian bioethics and for faithful Christian practice. [ABSTRACT FROM AUTHOR]

People often take psychiatric medication in order to obtain both freedom from painful experience and freedom for relationships and vocation. Thomas Aquinas' account of agency and freedom offers resources for using medications wisely. For Aquinas, bodily health is only the beginning of freedom. True freedom—always realized imperfectly in this life and perfected only with the assistance of grace—emerges when the acting person consistently pursues life-giving ends and develops habits to act for these ends with ease and pleasure. Psychiatric medications can encourage agency and freedom by correcting pathological processes, by relieving incapacitating suffering, and perhaps by lowering barriers to habituation in virtue, but they can also discourage agency and freedom by inhibiting morally salient emotional responses, by facilitating avoidance of pathological social contexts, and by reinforcing biological determinism. Psychiatric medications must be used only in ways that attend to social context and that encourage the cultivation of healthy agency. [ABSTRACT FROM AUTHOR]

Aim The aim was to analyze (i) the prevalence of online unwanted sexual solicitation (USS) victimization, (ii) predictors of online USS and (iii) the associations between online USS and depressive symptoms in Swedish pupils in grades 7–9. Methods An electronic questionnaire was disseminated in 2011 in schools in a municipality in the northern part of Sweden. Total n = 1193 (boys n = 566; girls n = 627). Logistic regression models were fitted to test the cross-sectional associations between predictors of online USS and depressive symptoms, respectively. Results One third of girls and every fifth boy reported online USS victimization. In boys, predictors associated with online USS were offline bullying and sexual harassment victimization. Only offline sexual harassment victimization was associated with online USS in girls. Girls victimized by online USS had about twice the likelihood to report depressive symptoms compared to non-victimized girls. There were no associations between online USS and depressive symptoms in boys. While offline bullying was associated with depressive symptoms in both genders, offline sexual harassment victimization increased the likelihood to report depressive symptoms in girls only. Conclusions Online USS was common among Swedish youth, particularly among girls. Schools, parents and internet safety educators should look at co-occurrence of different forms of victimization as offline victimization was a predictor of online USS. Online USS was associated with depressive symptoms in girls and may hence be a factor driving gender inequity in mental health in youth. [ABSTRACT FROM AUTHOR]

Background Three main explanations of the relationship between income and population health have been identified: the absolute, the contextual and the relative income hypotheses. The evidence about their relevance particularly in egalitarian societies is, however, inconsistent. This study aimed to test the three hypotheses in relation to psychological distress in northern Sweden. Methods Data come from the 2014 cross-sectional survey from the four northern-most counties in Sweden, and included people aged 25–84 years (n = 21 004). Psychological distress was measured by the General Health Questionnaire-12 and income information came from population registers. Absolute income was operationalized by individual disposable income, contextual income as the municipal-level Gini coefficient and relative income by the Yitzhaki index. Prevalence ratios (PR) were calculated from log-binomial regression analyses. Results A gradient in poor mental health was observed across quintiles of individual income, with the poorest substantially more likely to report poor health compared with the highest quintile (PR = 1.56; 95% CI = 1.19, 2.04). Second, municipalities in the quintiles 2–3 of the Gini coefficient had a better mental health compared with those in the most equal municipalities. Third, a gradient in poor mental health across quintiles of relative deprivation was also found, with the most deprived quintile the most likely to report poor health (PR = 1.37; 95% CI = 1.06, 1.76). Conclusion This study suggests a strong, moderate and lack of support for the absolute, relative and contextual income effect hypotheses, respectively. Interventions targeting a reduction in the individual income gap may be necessary in order to reduce psychosocial distress differences in northern Sweden. [ABSTRACT FROM AUTHOR]

Background In accordance with the policy actions that address childhood overweight and obesity at European level and as a contribution to the EU Action Plan on Childhood Obesity 2014–20, a Joint Action on Nutrition and Physical Activity (JANPA) was established. As part of JANPA work package 6, an evaluation framework to identify good practices, targeting childhood obesity prevention in kindergartens and schools, was developed. This article describes the WP 6 JANPA framework of good practice criteria and its development, compares it to other frameworks and discusses its potential for future use. Methods Based on the analysis of scientific literature, a set of 47 potential good practice criteria was drafted, that was then revised and complemented through a series of online Delphi consultations. Results A final list of 48 good practice criteria (9 of which were rated as core criteria) was developed and grouped into three categories: intervention characteristics (n = 17), implementation (n = 17) and monitoring and evaluation (n = 14). Conclusion The identified JANPA framework of good practice criteria complements the existing frameworks by focussing on kindergarten- and school-based initiatives and provides guidance for evaluators, programme planners and decision makers bearing in mind that a one-size-fits-all approach is inadequate. To ensure the effectiveness of future practices, programme planners should endeavour to meet at least the nine JANPA core criteria. [ABSTRACT FROM AUTHOR]

Background The current economic context calls for rationalizing health resources that can be pursued through disinvestment from low value health technologies to invest in the best performing ones, ensuring high healthcare quality. Oncology is a field where, because of high costs of health technologies and rapid innovation, disinvestment is crucial. Methods On this basis, the research team investigated through a survey, based on a questionnaire, opinions and views of representatives of European countries about disinvestment, in terms of fields of application, potential advocates and barriers, specifically focusing on cancer care. Results A total of 17 questionnaires were filled in (response rate: 32.1%). The survey showed disinvestment is applied in several countries as a tool for containing health care expenditures and identifying obsolete technologies/ineffective interventions. Clinicians' resistance to change and industries' opposition are recognized as the most important barriers to the implementation of disinvestment policies. Potential targets of disinvestment in cancer are seen in diagnostic and therapeutic areas. Conclusion Despite the agreement on fields of waste and of disinvestment policies, operational methods to put disinvestment in place are lacking. Since they should rely on an inclusive assessment of the technology, Health Technology Assessment may represent a good approach. [ABSTRACT FROM AUTHOR]

Background Schizophrenia is a chronic disease associated with significant and long-lasting effects on health, and it is also a social and financial burden, not only for patients but also for families, other caregivers, and the wider society. It is essential to conduct the assessment of indirect costs, to understand all the effects of the disease on society. Our aim is to gain a better understanding of the indirect costs of schizophrenia in Europe. Methods We conducted a comprehensive systematic literature review covering EMBASE, Medline, and PsycINFO as well as reviewing Health Technology Assessment databases from different countries. We used a qualitative research synthesis for presenting information, as most of the studies were methodologically diverse, a quantitative analysis would have been impractical. Results Indirect cost adjusted to inflation ranged vastly between studies included in the review from 119 Euros to 62, 034 Euros annually. The average proportion of indirect costs of total costs was 44%. Studies highlighted important cost drivers as age, gender, and disease severity, explaining the variation in costs between treatment and patient groups. Conclusions Regardless of the methodological heterogeneity of the reviewed studies, there was an agreement about the significance of indirect costs of schizophrenia on the society. Considering the relatively high prevalence of schizophrenia in Europe, a need for more cost of illness studies especially from Central Eastern and Southern Europe is suggested. [ABSTRACT FROM AUTHOR]

Background Socioeconomically disadvantaged children often have psychosocial problems. This study examined the mediating role of maternal depressive symptoms during pregnancy, infancy and early childhood in the association between maternal education, as indicator of socioeconomic status (SES), and child's psychosocial problems. Methods Included were 3410 children from the Amsterdam Born Children and their Development (ABCD) study. To assess the child's psychosocial problems at age 5–6 years, mothers and teachers completed the Strengths and Difficulties Questionnaire (SDQ). Maternal depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale and the Depressive Anxiety and Stress Scale 21. Mediation analysis was performed to calculate the direct effect of maternal education on SDQ score and indirect effects through maternal depressive symptoms. Results The mean mother-reported SDQ total score was significantly higher (P < 0.001) for children of low-educated mothers (6.74 ± 4.41) compared with children of highly educated mothers (4.47 ± 3.73). Levels of maternal depressive symptoms were also higher in low-educated mothers during pregnancy, infancy and early childhood. Maternal depressive symptoms explained 27.5% of the association between maternal education and mother-reported SDQ scores and 22.9% for combined mother/teacher SDQ scores. Maternal depressive symptoms during pregnancy had the strongest indirect effect. Conclusion Maternal depressive symptoms during pregnancy mediate the association between low maternal education and child's psychosocial problems. Early recognition and treatment of maternal depressive symptoms is important to prevent psychosocial problems in children, especially in those with low education. [ABSTRACT FROM AUTHOR]

Background There is still significant uncertainty as to whether market competition raises or lowers clinical quality in publicly funded healthcare systems. We attempted to assess the effects of market competition on inpatient care quality of stroke patients in a retrospective study of the universal single-payer health insurance system in Taiwan. Methods In this 11-year population-based study, we conducted a pooled time-series cross-sectional analysis with a fixed-effects model and the Hausman test approach by utilizing two nationwide datasets: the National Health Insurance Research Database and the National Hospital and Services Survey in Taiwan. Patients who were admitted to a hospital for ischemic or hemorrhagic stroke were enrolled. After excluding patients with a previous history of stroke and those with different types of stroke, 247 379 ischemic and 79 741 hemorrhagic stroke patients were included in our analysis. Four outcome indicators were applied: the in-hospital mortality rate, 30-day post-operative complication rate, 14-day re-admission rate and 30-day re-admission rate. Results Market competition exerted a negative or negligible effect on the medical care quality of stroke patients. Compared to hospitals located in a highly competitive market, in-hospital mortality rates for hemorrhagic stroke patients were significantly lower in moderately (β = –0.05, P < 0.01) and less competitive markets (β = –0.05, P < 0.01). Conversely, the impact of market competition on the quality of care of ischemic stroke patients was insignificant. Conclusions Simply fostering market competition might not achieve the objective of improving the quality of health care. Other health policy actions need to be contemplated. [ABSTRACT FROM AUTHOR]

Background Determinants of hypertension diagnosis and/or awareness and control among older adults are understudied in Albania, a former communist country in South Eastern Europe, which is experiencing rapid demographic, socioeconomic and epidemiological transition. This paper examines the association of individual, interpersonal, organizational and community factors with hypertension awareness and control among older adults in Tirana, the Albanian capital. Methods Using 2012 International Mobility in Aging Study data on older adults from Albania's capital city (n = 393) and the socioecological model as a conceptual framework, multinomial regression models identified factors associated with controlled, uncontrolled and undiagnosed hypertension. Results For hypertension, 17.3% participants had none, 23.4% were controlled, 48.4% were uncontrolled and 10.9% were undiagnosed/unaware. Compared to those with controlled hypertension, in multivariable models, a high level of friend support was negatively associated with uncontrolled (OR: 0.4; 95% CI: 0.2–0.9) and undiagnosed (OR: 0.2; 95% CI: 0.1–0.6) hypertension. A high level of perceived neighbourhood safety was negatively associated with uncontrolled (OR: 0.6; 95% CI: 0.3–1.0) and undiagnosed (OR: 0.4; 95% CI: 0.2–1.0) hypertension. Compared to those with no hypertension, children's social support was positively associated with uncontrolled (OR: 2.2; 95% CI: 1.1–4.3) and undiagnosed (OR: 3.6; 95% CI: 1.3–9.6) hypertension. Conclusion This study provides new insights about distinct risk factors for inadequate hypertension management in Albania. It highlights the importance of community-level factors (safety) and interpersonal factors (family and friend ties) to hypertension diagnosis/awareness and control, which may provide novel intervention opportunities for hypertension programs. [ABSTRACT FROM AUTHOR]

Background Starting in 2008 recession affected many European countries and especially Greece. Previous studies have reported increases in low birth weight, preterm birth and stillbirth rates in Greece during early crisis. In our study we used data on births from 1980 to 2014 that allowed us to distinguish recent changes, which could possibly be attributed to the financial crisis, from long term trends, and controlled for maternal age and country of origin as potential confounders. Our study covered a longer period (up to 2014) than what has been studied before and looked separately at the effect of early and established crisis. Methods We used national vital statistics data from 1980 to 2014. We performed age standardization and calculated age standardized rates and standardized rate ratios (SRRs) for perinatal factors for three time periods (pre-crisis, early crisis and established crisis) for Greek and non-Greek women. Results We found an increase in low birth weight deliveries independent of maternal age and origin and an increased stillbirth rate in Greek women younger than 25 in early (RR = 1.42 95%CI: 1.12–1.80) and established crisis periods (RR = 1.36 95%CI: 1.07–1.72) compared with pre-crisis. Non-Greek women have also been affected, with their advantage regarding birth outcomes becoming less profound in the established crisis period (low birth weight: established crisis SRR = 0.84 95%CI: 0.82–0.87, pre-crisis SRR = 0.79 95% CI: 0.76– 0.81). Conclusions The financial crisis has possibly adversely affected perinatal factors in Greece. Our results highlight the need of appropriate public health interventions and family support policies, especially for younger people, unemployed and immigrants. [ABSTRACT FROM AUTHOR]

Introduction: Three-quarters of homeless people smoke cigarettes. Financial incentives for smoking abstinence have appeared promising in nonexperimental studies of homeless smokers, but randomized controlled trial (RCT) data are lacking.Methods: We conducted a pilot RCT of financial incentives for homeless smokers. Incentive arm participants (N = 25) could earn escalating $15-$35 rewards for brief smoking abstinence (exhaled carbon monoxide <8 parts per million) assessed 14 times over 8 weeks. Control arm participants (N = 25) were given $10 at each assessment regardless of abstinence. All participants were offered nicotine patches and counseling. The primary outcome was a repeated measure of brief smoking abstinence across 14 assessments. The secondary outcome was brief abstinence at 8 weeks. Exploratory outcomes were self-reported 1-day and 7-day abstinence from (1) any cigarette and (2) any puff of a cigarette. Other outcomes included 24-hour quit attempts, nicotine patch use, counseling attendance, and changes in alcohol and drug use.Results: Compared to control, incentive arm participants were more likely to achieve brief abstinence overall (odds ratio 7.28, 95% confidence interval 2.89 to 18.3) and at 8 weeks (48% vs. 8%, p = .004). Similar effects were seen for 1-day abstinence, but 7-day puff abstinence was negligible in both arms. Incentive arm participants made more quit attempts (p = .03). Nicotine patch use and counseling attendance were not significantly different between the groups. Alcohol and drug use did not change significantly in either group.Conclusions: Among homeless smokers, financial incentives increased brief smoking abstinence and quit attempts without worsening substance use. This approach merits further development focused on promoting sustained abstinence.Registration: ClinicalTrials.gov (NCT02565381).Implications: Smoking is common among homeless people, and conventional tobacco treatment strategies have yielded modest results in this population. This pilot RCT suggests that financial incentives may be a safe way to promote brief smoking abstinence and quit attempts in this vulnerable group of smokers. However, further development is necessary to translate this approach into real-world settings and to promote sustained periods of smoking abstinence. [ABSTRACT FROM AUTHOR]

Introduction: Smartphone applications (apps) for smoking cessation are becoming increasingly available, but their efficacy remains to be demonstrated. We conducted a pilot study of SmokeBeat, a novel app designed for use with smartwatches and wristbands. SmokeBeat is powered by a data analytics software platform that processes information from the sensors embedded in wearables. It relies on an original algorithm to identify in real time the hand-to-mouth gestures that characterize smoking a cigarette. We examined whether merely monitoring and notifying smokers on smoking episodes in real time via the SmokeBeat app would lead to reduction in smoking.Methods: Forty smokers (9 women and 31 men) who expressed a wish to reduce or quit smoking were randomly assigned to using the SmokeBeat app for 30 days or to a wait-list control group. All participants completed questionnaires at baseline and at the end of the study, including their level of smoking. Smokers in the experimental condition were notified whenever the SmokeBeat system detected a smoking episode and were asked to confirm or deny it.Results: The SmokeBeat algorithm correctly detected over 80% of the smoking episodes and produced very few false alarms. According to both self-report and detection of smoking episodes by the SmokeBeat system, smokers in the experimental condition showed a significant decline in smoking rate over the 30-day trial (p < .001). There was no change in the smoking rate of the control group.Conclusion: These preliminary results suggest that automatic monitoring of smoking episodes and alerting the smoker in real time may facilitate smoking reduction in motivated smokers.Implications: Raising the awareness of smokers to the act of smoking in real time, as the SmokeBeat app is able to do, can counter the automaticity of the smoking habit. Bringing smoking under conscious awareness may benefit smokers who are motivated to reduce or quit smoking to gain better control of their smoking behavior and reduce cigarette intake. [ABSTRACT FROM AUTHOR]

Introduction Inadequate smoking cessation interventions by physicians have been attributed to lack of training, and it is generally thought that additional education will improve patient care. However, interventions aimed at increasing knowledge and practical skills only address one determinant of behavior (capability). This prospective study assessed how much a teaching session for general practitioner (GP) trainees enrolled in Vocational Training Schemes in England also affected two other determinants (motivation and opportunity) specified by the COM-B theory of behavior. Methods Between October and December 2015, GP trainees were given a 3.5-h training session in the theory and practice of smoking cessation. Questionnaires addressed motivation, capability, and opportunities to provide evidence-based brief advice to smokers at the beginning and end of the session, and 3 months later. They also looked at the recollection of previous teaching as well as knowledge, skills, intervention frequency, and perceived barriers against providing interventions. Results Participants (n = 123) remembered little previous training on the subject and self-reported presession knowledge was minimal. Motivation was high throughout while capability and opportunity increased considerably during the session. No further change in these parameters was noted at 3 months. The proportion of participants stating they provided evidence-based brief advice to >50% of smokers increased from 25.2% before the session to 57.7% at follow-up. Lack of time remained a commonly cited barrier. Conclusions Training elicited an immediate and sustained effect on capability, perceived opportunity, and behavior itself. While perceived barriers referring to capability were greatly reduced, barriers referring to opportunity (eg, lack of time) persisted. Implications This is the first study evaluating a GP training session on smoking cessation with regard to the COM-B model. In a pre-post design with 3-month follow-up, we observed substantial and sustained changes in GP trainees' perceived capability and opportunity to provide evidence-based very brief advice, and these increases were paralleled by favorable changes in practice behavior. [ABSTRACT FROM AUTHOR]

Introduction: Disparities in receiving advice to quit smoking and other tobacco use from health professionals may contribute to the continuing gap in smoking prevalence among priority populations. Under the Affordable Care Act (ACA), beginning in 2010, tobacco cessation services are currently covered in private and public health insurance plans. Providers and hospitals are also incentivized through the Meaningful Use of Electronic Health Records (EHRs) to screen and document patients' tobacco use and deliver brief cessation counseling. This study analyzes trends and correlates of receiving health professionals' advice to quit and potential disparities among US adult smokers from 2010 to 2015.Methods: Data were from the National Health Interview Survey in 2010 and 2015. We analyzed the weighted prevalence of smokers' receipt of advice to quit smoking and other tobacco use from a health professional in 2010 and 2015 and correlates of receiving advice to quit.Results: Prevalence of receiving advice to quit from a health professional increased from 51.4% in 2010 to 60.6% in 2015. This positive trend was observed across tobacco disparity population groups. Survey year (2015), age (older), ethnicity (non-Hispanic), region (Northeast), poverty level (above 100% poverty level), past quit attempt, daily smoking, cigarettes per day (11+ per day), and psychological distress were associated with higher odds of receiving advice to quit.Conclusion: Based on national level data, receipt of advice to quit from health professionals increased between 2010 and 2015. However, disparities in receiving advice to quit from health professionals persist in certain populations.Implications: This study provides important data on the national trends in receipt of health professional advice to quit smoking and other tobacco use in the context of the ACA and Meaningful Use implementation and whether these policies helped to narrow the gaps in receipt of health professional advice among vulnerable populations. [ABSTRACT FROM AUTHOR]

Objectives To conduct a clinicopathologic study of male breast carcinoma with Magee equation recurrence score (RS). Methods Seventy-four cases of male invasive breast cancers (MBCs) were studied, including 63 hormone receptor (HR)-positive, 10 human epidermal growth factor receptor 2-positive, and one triple-negative breast cancers. Results Among 63 HR-positive MBC patients, nine patients developed distal metastasis. Statistical analysis demonstrated distal metastasis was significantly associated with positive lymph node, high Nottingham grade, and increased Magee equation RS. All HR-positive MBCs were further stratified into two categories (low RS <18; intermediate/high RS ≥18). There was a significantly increased risk for distal metastasis in MBCs with intermediate/high Magee equation RS, but no increased risk for lymph node metastasis. Conclusions Our data suggest Magee equation RS may be useful to predict distal metastatic risk in MBC patients. [ABSTRACT FROM AUTHOR]

Objectives: To analyze consistency of reference limits and widths of reference intervals (RIs) calculated by six procedures and evaluate a protocol for merging intrainstitutional reference data.Methods: The differences between reference limits were compared with "optimal" bias goals. Also, widths of the RIs were compared. RIs were calculated using Mayo-SAS quantile, EP Evaluator, and four International Federation of Clinical Chemistry and Laboratory Medicine methods: parametric and nonparametric (NP) with and without latent abnormal values exclusion (LAVE). Regression parameters from cotested samples were evaluated for harmonizing intrainstitutional reference data.Results: Mayo-SAS quintile, LAVE(-)NP, and EP Evaluator generated similar RIs, but these RIs often were wider than RIs from parametric procedures. LAVE procedures generated narrower RIs for nutritional and inflammatory markers. Transformation with regression parameters did not ensure homogeneity of merged data.Conclusions: Parametric methods are recommended when inappropriate values cannot be excluded. The nonparametric procedures may generate wider RIs. Data sets larger than 200 are recommended for robust estimates. Caution should be exercised when merging intrainstitutional data. [ABSTRACT FROM AUTHOR]

Objectives: Ethanol is a widely consumed drug in almost every society. In this study, the potential interfering effect of ethanol on routine biochemical tests was evaluated.Methods: Serum pools were prepared from blood samples collected from patients seeking treatment at the emergency department. Five separate groups were formed by adding ethanol to the samples, so the final concentrations were negative: 50 mg/dL, 100 mg/dL, 200 mg/dL, and 400 mg/dL. Each group was divided into 20 portions, and routine biochemical tests were measured from each portion. The coefficient of variation (CV), bias, and total error values were calculated for the measured parameters.Results: Alanine aminotransferase (ALT; EC 2.6.1.2) and lactate dehydrogenase (LDH; EC 1.1.1.27) activities decreased in proportion to the ethanol level. High negative biases were observed, suggesting a dose-dependent negative interference. The total error values calculated for direct bilirubin and urea were higher than the allowable total error reported in the Clinical Laboratory Improvement Amendments of 1988. For direct bilirubin, it was observed that the cause of this shift was due to the increase in CV values.Conclusions: We conclude that ethanol may cause interference in the measurement of some biochemical tests, whereas the most prominent effect was observed for LDH and ALT. [ABSTRACT FROM AUTHOR]

Objectives: The eighth edition of the American Joint Committee on Cancer staging manual now stratifies nonmucinous lung adenocarcinomas (nmLACAs) by the size of the invasive component only. This is determined by direct gross or microscopic measurement; however, a calculated invasive size based on the percentage of invasive growth patterns has been proposed as an alternative option.Methods: To compare radiologic with different pathologic assessments of invasive tumor size, we retrospectively reviewed a cohort of resected nmLACAs with a part-solid appearance on computed tomography (CT) scan (n = 112).Results: The median direct microscopic pathologic invasive measurements were not significantly different from the median calculated pathologic invasive measurements; however, the median CT invasive measurements were 0.26 cm larger than the median direct pathologic measurements (P < .001).Conclusions: Our results show that pathologic calculated invasive tumor measurements are comparable to direct microscopic measurements of invasive tumor, thereby supporting the recommendation for use of calculated invasive tumor size by the pathologist if necessary. [ABSTRACT FROM AUTHOR]

In this study, tribal members from an American Indian (AI) community in the midwestern United States used photovoice, a community-based participatory method, to document their perceptions and beliefs about water and health on their reservation. The study infused photovoice's seminal theoretical influences within an environmental justice framework to explore the impact of environmental changes in water on human health and well-being. Study participants included two men and nine women who self-identified as tribal members and either worked or lived (or both) on their tribe's reservation. During the photovoice project, participants took photographs and engaged in face-to-face interviews using the SHOWeD technique to reflect on the images they had captured. An In Vivo coding method was used to code the data using participants' own words, followed by a thematic analysis to contextualize the codes within the cultural realities of the tribal community. Study findings detail how water is fundamental to the lives of the AI study participants and expose the scope of health concerns they have related to water circumstances on their reservation. The article concludes with a discussion about the use of photovoice with AI communities and implications of using the method for social work practice and research. [ABSTRACT FROM AUTHOR]

Prediction is often the primary goal of data analysis. In this work, we propose a novel model averaging approach to the prediction of a functional response variable. We develop a crossvalidation model averaging estimator based on functional linear regression models in which the response and the covariate are both treated as random functions. We show that the weights chosen by the method are asymptotically optimal in the sense that the squared error loss of the predicted function is as small as that of the infeasible best possible averaged function. When the true regression relationship belongs to the set of candidate functional linear regression models, the averaged estimator converges to the true model and can estimate the regression parameter functions at the same rate as under the true model. Monte Carlo studies and a data example indicate that in most cases the approach performs better than model selection. [ABSTRACT FROM AUTHOR]

Sliced inverse regression is a popular tool for sufficient dimension reduction, which replaces covariates with a minimal set of their linear combinations without loss of information on the conditional distribution of the response given the covariates. The estimated linear combinations include all covariates, making results difficult to interpret and perhaps unnecessarily variable, particularly when the number of covariates is large. In this paper, we propose a convex formulation for fitting sparse sliced inverse regression in high dimensions. Our proposal estimates the subspace of the linear combinations of the covariates directly and performs variable selection simultaneously. We solve the resulting convex optimization problem via the linearized alternating direction methods of multiplier algorithm, and establish an upper bound on the subspace distance between the estimated and the true subspaces. Through numerical studies, we show that our proposal is able to identify the correct covariates in the high-dimensional setting. [ABSTRACT FROM AUTHOR]

Time-to-event outcomes are often evaluated on the hazard scale, but interpreting hazards may be difficult. Recently in the causal inference literature concerns have been raised that hazards actually have a built-in selection bias that prevents simple causal interpretations. This is a problem even in randomized controlled trials, where hazard ratios have become a standard measure of treatment effects. Modelling on the hazard scale is nevertheless convenient, for example to adjust for covariates; using hazards for intermediate calculations may therefore be desirable. In this paper we present a generic method for transforming hazard estimates consistently to other scales at which these built-in selection biases are avoided. The method is based on differential equations and generalizes a well-known relation between the Nelson–Aalen and Kaplan–Meier estimators. Using the martingale central limit theorem, we show that covariances can be estimated consistently for a large class of estimators, thus allowing for rapid calculation of confidence intervals. Hence, given cumulative hazard estimates based on, for example, Aalen's additive hazard model, we can obtain many other parameters without much more effort. We give several examples and the associated estimators. Coverage and convergence speed are explored via simulations, and the results suggest that reliable estimates can be obtained in real-life scenarios. [ABSTRACT FROM AUTHOR]

In paired randomized experiments, individuals in a given matched pair may differ on prognostically important covariates despite the best efforts of practitioners. We examine the use of regression adjustment to correct for persistent covariate imbalances after randomization, and present two regression-assisted estimators for the sample average treatment effect in paired experiments. Using the potential outcomes framework, we prove that these estimators are consistent for the sample average treatment effect under mild regularity conditions even if the regression model is improperly specified, and describe how asymptotically conservative confidence intervals can be constructed. We demonstrate that the variances of the regression-assisted estimators are no larger than that of the standard difference-in-means estimator asymptotically, and illustrate the proposed methods by simulation. The analysis does not require a superpopulation model, a constant treatment effect, or the truth of the regression model, and hence provides inference for the sample average treatment effect with the potential to increase power without unrealistic assumptions. [ABSTRACT FROM AUTHOR]

Multiple types of data measured on a common set of subjects arise in many areas. Numerous empirical studies have found that integrative analysis of such data can result in better statistical performance in terms of prediction and feature selection. However, the advantages of integrative analysis have mostly been demonstrated empirically. In the context of two-class classification, we propose an integrative linear discriminant analysis method and establish a theoretical guarantee that it achieves a smaller classification error than running linear discriminant analysis on each data type individually. We address the issues of outliers and missing values, frequently encountered in integrative analysis, and illustrate our method through simulations and a neuroimaging study of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

We consider a heteroscedastic regression model in which some of the regression coefficients are zero but it is not known which ones. Penalized quantile regression is a useful approach for analysing such data. By allowing different covariates to be relevant for modelling conditional quantile functions at different quantile levels, it provides a more complete picture of the conditional distribution of a response variable than mean regression. Existing work on penalized quantile regression has been mostly focused on point estimation. Although bootstrap procedures have recently been shown to be effective for inference for penalized mean regression, they are not directly applicable to penalized quantile regression with heteroscedastic errors. We prove that a wild residual bootstrap procedure for unpenalized quantile regression is asymptotically valid for approximating the distribution of a penalized quantile regression estimator with an adaptive |$L_1$| penalty and that a modified version can be used to approximate the distribution of a |$L_1$| -penalized quantile regression estimator. The new methods do not require estimation of the unknown error density function. We establish consistency, demonstrate finite-sample performance, and illustrate the applications on a real data example. [ABSTRACT FROM AUTHOR]

The aim of this article is to shed light on the decision-making process at university technology transfer offices and show that the last steps in the process of international patent extension, when costs step up, tend to be only taken conditional on the existence of a licensing agreement. This information has so far been underexploited by policymakers and innovation scholars in search of innovation indicators. We argue that the number of international patent families filed by a university can be used as a rough indicator of technology transfer activity mediated through patents, especially in the context of tight public university budgets and national patent systems with fee reductions for universities. To support our argument, we review qualitative information from interviews at technology transfer offices, regulations, and internal statutes from a selection of Spanish universities and present a statistical analysis of the relation between patent internationalisation and licensing. [ABSTRACT FROM AUTHOR]

This study presents an analysis of 2,216 European higher education institutions (HEIs) from 27 countries. It investigates determinants of participation in the European Union's Framework Programme for research and innovation (EU FP), Horizon 2020, and empirically assesses how influential network position affects the chances of applying for and receiving funding in collaborative projects. Having a strong, influential network position in collaborative EU research is found to affect participation in H2020 greatly—suggesting 'closed clubs', to the detriment of less influential HEIs. Greater access to resources and capabilities significantly strengthens the effect of network position on EU FP participation. [ABSTRACT FROM AUTHOR]

This article aims to provide a deeper understanding of the individual factors behind scientists' involvement in a wide variety of knowledge transfer and exchange (KTE) activities. By doing so, the article addresses three major shortcomings in the literature. First, this article considers scientists' involvement in both formal and informal KTE activities. Secondly, the study focuses not only on KTE activities with the private sector, but also with other types of agents. Thirdly, the article adopts an individual approach to distinguish between three types of KTE predictors: individual capacities, training and career trajectories, and motivations. Overall, the results of the regression model applied to a sample of 1,295 researchers active in the largest public research organization in Spain (CSIC) suggest that, while some individual features are connected to some KTE activities, other individual predictors (e.g. multitasking and interdisciplinarity) are more evenly associated to a variety of KTE mechanisms and users. Based on those findings, the article offers policy recommendations to craft more accurate policies to encourage scientists' KTE engagement. [ABSTRACT FROM AUTHOR]

This article describes a methodology for analysing the diffusion of scientific information into the social sphere, termed the 'scientific knowledge percolation process'. The methodology was built using automated data collection and lexicon-based data mining techniques. We analysed literature from the scientific biotechnology community (158 journals in 2011; 29,892 articles generating 50,591 different keywords) and how it is perceived by users of the social media site Twitter (375,660 tweets with a subset classified by sentiment (positive, negative, and neutral) for a total of 33,900 tweets for 2012). We show that our method is able to provide data from which we can draw robust conclusions concerning the relationship between scientific and social media information. The study shows that the scientific production of our subset is socially perceived in a neutral manner although it is skewed towards the negative. Because sentiments are relevant for explaining the sharing behaviour of social media users, the results suggest that more attention needs to be paid towards the social perceptions of scientific research. We found that similar scientific concepts can be socially perceived in different ways, which may suggest that there is room for scientists to choose more 'socially friendly' descriptions. [ABSTRACT FROM AUTHOR]

Organic poultry production is based on ecological processes, such as nutrient cycling, and reduces the use of synthetic inputs. High-quality protein feeds are needed to provide essential amino acids for poultry, particularly methionine. Although synthetic methionine is currently allowed in poultry feeding in the US organic program, sources that are natural are needed. Fishmeal is a high-quality protein and contains methionine; however, fishmeal sources are limited and may not be sustainable or local. A possible source of fishmeal in the USA is Asian carp fishmeal. Asian carp have invaded the Mississippi river basin with negative impacts on native fish and riparian ecosystems, and harvesting the carp may be a management strategy to help control it. Additional options for high-quality protein feeds include invertebrate meals from mass insect production, such as black soldier fly larvae, and worms. These can be raised sustainably for poultry feed by using crop by-products, residues, or recycled food to reduce food waste. Alternative feeding methods may be helpful to utilize these innovative feeds. Alternative protein feeds can contribute to ecological poultry production and have an important role under certified organic standards. [ABSTRACT FROM AUTHOR]

Campylobacter is a human food-borne pathogen frequently associated with poultry and poultry products and can be found in high numbers within the gut contents of colonized broilers. The number of Campylobacter on broiler carcasses increases markedly during automated defeathering as rubber picker fingers press on the abdomen and can force gut contents out of the cloaca. One method to prevent this increase is to plug the cloaca and prevent escape of gut contents. For a plug to be effective, it must resist expulsion during picking. In the current work, we test shredded sponge or paper as a means to plug broiler carcass cloacae during automated feather removal. Broiler carcass cloacae were plugged before scalding and carcasses were sampled to determine the bacterial numbers present on breast skin after scalding (before feather picking) and again after feather picking. Neither 50 cc of shredded paper nor 25 cc of shredded sponge was effective as a cloacal plug. However, a plug made of 50 cc shredded sponge material was effective to occlude broiler carcass vents during automated defeathering. Significantly fewer Campylobacter cells were detected on the breast skin of post pick carcasses plugged with 50 mL of shredded sponge than on post pick unplugged control carcasses. [ABSTRACT FROM AUTHOR]

Past literature lacks studies that compare diets containing an improved feed form vs. an increased energy. The objective of the study was to assess the effect of variations of feed form and dietary caloric density on broilers reared on clean shavings and built-up litter. Treatments were arranged in a 2 × 2 factorial randomized block design within a split plot. Whole plot treatments considered one room (11 × 7.32 m) of either clean shavings or built-up litter; divided into 16 treatment replications of either standard (30%) or improved (80% feed form), and 16 replications of either commercial or increased (+110 kcal/kg) dietary caloric density comprising the 2 × 2 factorial arrangement. Broilers consuming an improved feed form demonstrated an improved feed intake, live weight gain, feed conversion ratio, breast weight and breast yield (P < 0.05). Providing an improved feed form demonstrated an upregulation in IgG (P < 0.05). An environment × energy interaction (P < 0.05) demonstrated upregulation of IgG in broilers fed a commercial energy reared in a built-up litter environment, whereas broilers maintained a similar regulation of IgG when fed an increased energy regardless of environment. Linear contrasts demonstrated that broilers provided improved feed form at commercial energy increased feed intake and live weight gain (P ≤ 0.05), while maintaining feed conversion ratio (P > 0.05) compared to broilers provided standard feed form at increased energy regardless of environment. These data suggest feed form improvements may partition energy towards growth more than feeding an increased energy diet. [ABSTRACT FROM AUTHOR]

Aim Although socioeconomic background is known to impact on the incidence and progression of chronic kidney disease, its influence of on the presentation and outcome for acute kidney injury is not known and is the subject of this study. Design The Welsh National electronic AKI reporting system was used to identify all cases of AKI in patients >18 years of age between March 2015 and November 2017. Methods Socioeconomic classification of patients was derived from the Welsh Index Multiple Deprivation score (WIMD). Patients were grouped according to the WIMD score by their postcode, and the ranked data were categorized into percentiles and correlated with incidence and measures of AKI severity and outcome. Results Date was collected on a total of 57 654 patients. Increased deprivation was associated with higher AKI incidence rates, more episodes of AKI per patient and more severe AKI at presentation. In contrast 90-day mortality was highest in the most affluent areas. Mortality in affluent areas was driven by increased patient age. Corrected for age 90-day mortality was higher in areas of increased deprivation. Conclusion This study highlights that AKI incidence presentation and outcomes are adversely affected by social deprivation. Further studies are required to understand the extent to which these differences reflect patient related factors or regional differences in provision and access to care. [ABSTRACT FROM AUTHOR]

Background: A perfect smile is dictated by the balance among 3 parameters: the white (teeth), the pink (gum), and the lips: excessive gingival display while smiling has been a cause of esthetic embarrassment for many patients, thus affecting their psychosocial behavior. With respect to different etiologies, treatment of gummy smile must be properly planned: treatment options include facial surgery, oral surgery, or laser.Objectives: Given the growing demand for less invasive techniques and observed complications secondary to botulinum toxin injection, we present a novel treatment option aimed at correcting gummy smile using hyaluronic acid injection and review the published techniques and the anatomy of the involved facial muscles.Methods: The treatment was performed by infiltration in the paranasal area, in the location of the most cranial portion of the nasojugal fold, about 3 mm lateral to the alar cartilage wing, according to a vector perpendicular to the cutaneous plane, to gently compress the lateral fibers of the levator labii superioris alaeque nasi without invading it. A Vycross® technology filler was used for all the treatments.Results: All patients had an immediate improvement, with a maximum duration ranging from 186 to 240 days (mean, 213 days), according to parameters of the Global Aesthetic Improvement Scale (GAIS 4.06).Conclusions: This new, less invasive and safer technique to correct dynamic excessive gingival display was shown to be feasible and safe with a long-lasting result. This treatment could be a novel effective option for experienced injectors to treat aesthetic facial flaws.Level of Evidence4: [ABSTRACT FROM AUTHOR]

Background: Umbilical hernia is a common finding in patients undergoing abdominoplasty, especially those who are postpartum with rectus divarication. Concurrent surgical treatment of the umbilical hernia at abdominoplasty presents a "vascular challenge" due to the disruption of dermal blood supply to the umbilicus, leaving the stalk as the sole axis of perfusion. To date, there have been no surgical techniques described to adequately address large umbilical herniae during abdominoplasty.Objectives: To present an effective and safe technique that can address large umbilical herniae during abdominoplasty.Methods: A prospective series of 10 consecutive patients, undergoing concurrent abdominoplasty and laparoscopic umbilical hernia repair between 2014 and 2017 were included in the study. All procedures were performed by the same general surgeon and plastic surgeon at the Macquarie University Hospital in North Ryde, NSW, Australia. Data were collected with approval of our ethics committee.Results: At 12-month follow up there were no instances of umbilical necrosis, wound complications, seroma, or recurrent hernia. The mean body mass index was 23.8 kg/m2 (range, 16.1-30.1 kg/m2). Rectus divarication ranged from 35 to 80 mm (mean, 53.5 mm). Umbilical hernia repair took a mean of 25.9 minutes to complete (range, 18-35 minutes).Conclusions: We present a technique that avoids incision of the rectus fascia minimizes dissection of the umbilical stalk and is able to provide a gold standard hernia repair with mesh. This procedure is particularly suited to postpartum patients with large herniae (>3-4 cm diameter) and wide rectus divarication, where mesh repair with adequate overlap is the recommended treatment.Level Of Evidence4: [ABSTRACT FROM AUTHOR]

This article reports a correspondence between input/output logic and the theory of joining-system, an algebraic approach to normative system. The results have the form: every norm (a, x) is logically derivable from a set of norms G if and only if it is in the space of norms algebraically generated by G. We present three versions of correspondence: input/output logic and Boolean joining-system, intuitionistic input/output logic and Heyting joining-system, quasi input/output logic and quasi joining-system. The algebraic approach offers a holistic perspective on normative systems. We use isomorphism and embedding of joining-system to discuss the similarity of normative systems. [ABSTRACT FROM AUTHOR]

In this article, we study a minimal change approach to preference dynamics. We treat a set of preferences as a special kind of theory, and define minimal change preference contraction and revision operations in the spirit of the Alchourrón, Gärdenfors, and Makinson theory of belief revision. We characterise minimal contraction of preference sets by a set of postulates and prove a representation theorem. We also give a linear time algorithm which implements minimal contraction by a single preference. We then define minimal contraction by a set of preferences, and show that the problem of a minimal contraction by a set of preferences is NP-hard. [ABSTRACT FROM AUTHOR]

Millions of dollars have been spent on the design and dissemination of educational materials to improve handwashing to prevent infectious diseases. School-age children have been the focus of many of these efforts; yet little is known about the content of these materials. This study uses content analysis to examine the theoretical and motivational trends as well as the communication approach used in a sample of hand hygiene intervention materials targeting elementary-age children. Two trained coders analyzed 144 communication materials. Study results indicate that educational materials infrequently exhibit information consistent with theories of communication for behavior change, commonly use fear-based messaging, and rarely recommend using technology in the design of the interventions. Implications for future research and the design of more strategic, child-focused hand hygiene interventions are discussed. [ABSTRACT FROM AUTHOR]

Yule and Burnell's famous Anglo-Indian glossary Hobson-Jobson was first published in 1886 and thence updated by William Crooke in 1903. It is still widely available today, and despite the fact that its contents are over a century out of date, it is still used as a reference work for Indian English. Since its publication it has generally received positive reviews and very little in the way of critical comment or analysis of the text. Moreover, the literature on Hobson-Jobson is beset by inaccurate statements or is otherwise couched in hedges due to a lack of precise knowledge about the dictionary's contents. This paper provides an overview of the critical attention Hobson-Jobson has received, summarises the editing and printing history, and then presents a wholly new analysis of the dictionary, bringing to light many previously unknown facts. [ABSTRACT FROM AUTHOR]

Background Closed and open surgical techniques are two different main approaches to surgical exposure of palatally displaced canines (PDCs). Because there is insufficient evidence to support one technique over the other, there is a need for randomized controlled trials. Objectives To compare surgery time, complications and patients' perceptions between closed and open surgical techniques in PDCs. Trial design The trial was a multicentre, randomized, controlled trial with two parallel groups randomly allocated in a 1:1 ratio. Material and methods Study participants were 119 consecutive patients from 3 orthodontic centres, with PDCs planned for surgical exposure, randomly allocated according to a computer-generated randomization list, using concealed allocation. Full-thickness mucoperiosteal flap was raised, and bone covering the canine was removed in both interventions. In closed exposure, an attachment with a chain was bonded to the canine and the flap was sutured back with the chain penetrating the mucosa. In open exposure, a window of tissue around the tooth was removed and glass ionomer cement placed on the canine crown, to prevent gingival overgrowth during spontaneous eruption. Patient perceptions were assessed with two questionnaires, for the evening on the day of operation and 7 days post-surgery. Blinding It was not possible to blind either patients or care providers to the interventions. The outcome assessors were blinded and were unaware of patients' intervention group. Results Seventy-five girls and 44 boys, mean age 13.4 years (SD 1.46) participated in the study and got either of the interventions (closed exposure, n = 60; open exposure, n = 59). Surgery time did not differ significantly between the interventions. Complications though were more severe in bilateral cases and the patients experienced more pain and impairment in the open group. Conclusion There were no statistically significant differences regarding surgery time between the groups. Postoperative complications were similar between the groups in unilateral PDCs, but more common in the open group in bilateral cases. More patients in the open group experienced pain and impairment compared to the closed group. Trial registration Trial registration: ClinicalTrials.gov, ID: NCT02186548 and Researchweb.org, ID: 127201. [ABSTRACT FROM AUTHOR]

Background and objectives The objective was to systematically review transalveolar transplantation of maxillary canines and the long-term outcome for an average follow-up period of 2 years or more. Data collection and analysis A systematic review of the currently available literature until December 2017 was conducted, using Medline, Cochrane Central, Web off Science, and PubMed. Articles were screened for 1. indications, 2. contra-indications, 3. surgical planning, 4. surgical technique, 5. associated risk factors, and 6. long-term outcome for transalveolar transplantation of maxillary canines with the following outcome measures: bone-related outcomes, tooth-related outcomes, soft tissue-related outcomes, and aesthetic outcome measures. Descriptive statistics, as well as a quality assessment of included articles, were performed. Following study retrieval and selection, relevant data was extracted and the risk of bias was assessed using the Methodological index for non-randomized studies (MINORS). Results Twelve articles were included in this review. These studies included outcome data for 783 autotransplanted maxillary canines, with long-term studies indicating a clinically acceptable overall outcome. Limitations Since the lack of randomized controlled trials considering this topic, the quality of the evidence in the present review is considered low. However, impacted maxillary canines are a rare anomaly and different aspects, such as position of the impacted canine, patient's age and patient's demands, and expectancies must be taken into account, it is practically impossible to randomize treatment. Conclusions There is sufficient evidence to justify the transalveolar transplantation of maxillary canines as a legitimate treatment technique for impacted maxillary canines deemed difficult to treat with surgical exposure and subsequent orthodontic alignment. Long-term studies have shown that a good overall outcome is to be expected. There is no clear agreement in the literature on the indications and contra-indications for transalveolar transplantation of maxillary canines. Implication of key findings It is highly desirable that further research on this issue be undertaken, high-quality observational studies are recommended. Registration PROSPERO (CRD42017056348) [ABSTRACT FROM AUTHOR]

The HLA Hart Memorial Lecture, delivered at Oxford on 9 May 2017, addresses the related questions of conflicts between rights and interests, between rights and other rights, and between or among interests. Using the metaphor of the eternally optimistic Dr Pangloss in Voltaire's Candide, the lecture and ensuing article identify a common Panglossian tendency of officials and commentators to understand (or distort) the facts about the empirical world so as to avoid conflicts with constraining rights, and to understand (and distort) the shape and definition of those constraining rights so as to avoid conflicts with interests. Such efforts may be understandable attempts by the commentators and officials to avoid cognitive dissonance and achieve cognitive consistency, but may nevertheless produce a warped understanding of the empirical world and of the contours of the rights that appropriately limit even the wise policies that officials may otherwise pursue. [ABSTRACT FROM AUTHOR]

Objectives: To provide detailed genetic characterization of four novel blaIMP-carrying transposons from Pseudomonas aeruginosa, Klebsiella pneumoniae and an Enterobacter sp.Methods: P. aeruginosa 60512, K. pneumoniae 447, P. aeruginosa 12939 and Enterobacter sp. A1137 were subjected to genome sequencing. The complete nucleotide sequences of two plasmids (p60512-IMP from the 60512 isolate and p447-IMP from the 447 isolate) and two chromosomes (the 12939 and A1137 isolates) were determined, then a genomic comparison of p60512-IMP, p447-IMP and four novel blaIMP-carrying transposons (Tn6394, Tn6375, Tn6411 and Tn6397) with related sequences was performed. Transferability of the blaIMP gene and bacterial antimicrobial susceptibility were tested.Results: Tn6394 and Tn6375 were located in p60512-IMP and p447-IMP, respectively, while Tn6411 and Tn6397 were integrated into the 12939 and A1137 chromosomes, respectively. Tn6394 was an ISPa17-based transposition unit that harboured the integron In992 (carrying blaIMP-1). In73 (carrying blaIMP-8), In73 and In992, together with the ISEcp1:IS1R-blaCTX-M-14-IS903D unit, the macAB-tolC region and the truncated aacC2-tmrB region, respectively, were integrated into the prototype transposons Tn1722, Tn1696 and Tn7, respectively, generating the Tn3-family unit transposons, Tn6375 and Tn6378, and the Tn7-family unit transposon Tn6411, respectively. Tn6397 was a large integrative and conjugative element carrying Tn6378.Conclusions: Complex events of transposition and homologous recombination have occurred during the original formation and further plasmid and chromosomal integration of these four transposons, promoting accumulation and spread of antimicrobial resistance genes. [ABSTRACT FROM AUTHOR]

Objectives: There is growing concern about mitochondrial DNA (mtDNA) mutations with long-term NRTI exposure in HIV-1 infected children.Methods: Twenty-four HIV-1 infected children who started ART more than 2 years earlier who had an excellent virological response and had not changed their regimen were enrolled retrospectively. Their corresponding PBMCs in 2009 (T1), 2010 (T2) and 2013 (T3) were included. Sequencing of the entire mtDNA using next-generation sequencing revealed the spectrum of mtDNA variants.Results: The trend showed that the number of mtDNA mutations during ART occurred as T1 < T2 < T3 (P = 0.086). Interestingly, the numbers of whole mtDNA mutations at T3 (median 41, range 24-62) were significantly greater than at T1 (34, 25-46, P = 0.029). A positive correlation was found between total mtDNA mutations and treatment time (r = 0.352, P = 0.002). During the observation period, mtDNA mutations more frequently occurred in the D-loop, cytochrome b (CYTB) and 12S rRNA regions. The heteroplasmic ratio of T3 was higher than that of T1 in CYTB and 12S rRNA (P = 0.034 and P = 0.042, respectively). High heteroplasmic population levels were found at nt 263 (A263G, D-loop) and nt 8860 (A8860G, ATPase6). A significant difference in heteroplasmy between T1, T2 and T3 occurred at nt 14783 (T14783C, CYTB, P = 0.048, T3 > T2 > T1).Conclusions: Our findings reveal the spectrum of mtDNA variants in HIV-1-infected children who had an excellent virological response. mtDNA mutations accumulated during ART may play an important role in facilitating the occurrence of mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Background: The ST131 Escherichia coli clone is associated with the global dissemination of ESBLs. It has been hypothesized that ST131 could take advantage of better colonizing abilities. However, the data on colonization prevalence of ESBL-ST131 in European hospitals are scarce.Objectives: To assess the prevalence of the ST131 clone and its microbiological characteristics among colonizing ESBL-producing E. coli (ESBL-Ec) from hospitalized patients in four European hospitals (Berlin, Geneva, Madrid and Utrecht) during the R-GNOSIS study.Methods: ESBL-Ec isolates (n = 688) were obtained from rectal swabs of hospitalized patients from March 2014 to February 2015 using selective media. The ST131 clone and its subclones were sought using PCR and positive isolates were further studied. blaESBL genes were characterized (PCR and sequencing), antibiotic susceptibility testing was performed, clonal relationships were studied by PFGE and fimH allele and O type (PCR) were assessed.Results: ST131 prevalence was 20.5% (141/688); C1/H30R1 isolates were significantly more prevalent in Geneva (49%) and C2/H30Rx in Madrid (67%). C1/H30R1 isolates showed less resistance to amikacin than C2/H30Rx (4% versus 35%) and all were susceptible to penicillin/inhibitor combinations. CTX-M-15 was the most common enzyme (49%) followed by CTX-M-27 (27%). C1/H30R1 isolates were significantly associated with CTX-M-27 (72%) and all of these isolates belonged to the C1-M27 clade. Moreover, C2/H30Rx isolates and CTX-M-15 were also significantly related (88%).Conclusions: The predominance of C2/H30Rx-CTX-M-15 in Madrid and C1/H30R1-CTX-M-27 in Geneva demonstrates a changing epidemiology of ESBLs in Europe caused by ST131 subclones; in particular, the emergence of the C1-M27 clade in Europe. [ABSTRACT FROM AUTHOR]

Background: Primary screening for VRE with PCR directed against vanA allowed identification of vanA+ samples from which VRE could not be isolated when selective culture methods were used. From such a sample a vancomycin-susceptible, vanA+ Enterococcus faecium, Efm-V1511, was isolated, when vancomycin selection was not used during culture. Similar isolates with variable susceptibility to vancomycin were obtained in the following months.Objectives: To characterize Efm-V1511 and investigate the causes of variable susceptibility to vancomycin.Methods: All strains were sequenced using Illumina technology. Plasmids containing vanA were reconstructed by scaffolding to known plasmids or plasmids were sequenced using Oxford Nanopore MinION. Derived structures were verified by PCR and sequencing. Furthermore, selected vanA+ vancomycin-susceptible isolates were passaged in the presence of vancomycin and vancomycin-resistant variants obtained were sequenced.Results: Efm-V1511 belonged to ST1421 and contained a 49 696 bp plasmid pHVH-V1511 carrying a Tn1546-derived genetic element. Within this element vanX was truncated by a 252 bp 3' deletion explaining the susceptibility of Efm-V1511. Between March 2016 and April 2017, 48 isolates containing pHVH-V1511 were identified. All were ST1421. In isolates resistant to vancomycin, resistance could be attributed to changes in ddl disrupting gene function sometimes accompanied by changes in vanS, increased pHVH-V1511 copy number or the existence of an additional vanA-containing plasmid encoding a functional vanX.Conclusions: E. faecium carrying pHVH-V1511 is capable of nosocomial transmission and may develop clinical resistance to vancomycin. Strains may not be detected using standard culture methods for VRE. [ABSTRACT FROM AUTHOR]

Background: Experience in real clinical practice with ceftazidime/avibactam is limited, and there are even fewer data on infections due to OXA-48-producing Enterobacteriaceae.Methods: We designed an observational study of a prospectively collected cohort of adult patients receiving ceftazidime/avibactam in our centre. Only the first treatment course of each patient was analysed. Efficacy and safety were evaluated as 14 and 30 day mortality, recurrence rate at 90 days, resistance development and occurrence of adverse effects.Results: Fifty-seven patients were treated with ceftazidime/avibactam. The median age was 64 years (range 26-86), 77% were male and the median Charlson index was 3. The most frequent sources of infection were intra-abdominal (28%), followed by respiratory (26%) and urinary (25%). Thirty-one (54%) patients had a severe infection (defined as presence of sepsis or septic shock). Most patients received ceftazidime/avibactam as monotherapy (81%) and the median duration of treatment was 13 days. Mortality at 14 days was 14%. In multivariate analysis, the only mortality risk factor was INCREMENT-CPE score >7 (HR 11.7, 95% CI 4.2-20.6). There was no association between mortality and monotherapy with ceftazidime/avibactam. The recurrence rate at 90 days was 10%. Ceftazidime/avibactam resistance was not detected in any case and only two patients developed adverse events related to treatment.Conclusions: Ceftazidime/avibactam shows promising results, even in monotherapy, for the treatment of patients with severe infections due to OXA-48-producing Enterobacteriaceae and limited therapeutic options. The emergence of resistance to ceftazidime/avibactam was not observed. [ABSTRACT FROM AUTHOR]