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ABSTRACTIntroductionAsthma is a common disease with a global burden of 358 million patients. Despite improvements in pharmacological and non-pharmacological treatments, many patients still do not achieve complete asthma control. Therefore, innovative pharmacotherapy is important.Areas coveredFollowing a semi-structured search in Pubmed, an overview of advances in inhaled asthma therapy is provided, looking at innovations in digital inhalers, eco-friendly inhalers and novel inhaled biologic therapies, antibiotics and vaccines, as well as other potential novel asthma therapy targets.Expert opinionDigital inhalers, sending reminders and monitoring inhalation technique electronically, can support medication adherence and improve asthma control. To reduce the global warming potential of traditional aerosols used in pressurized metered-dose inhalers (HFA-134a, HFA-227ea), greener alternatives are under development (HFA-152a, HFO-1234ze) that are expected to be available by 2025. Current pharmacological advances in asthma therapy are mainly achieved by novel biologicals (anti-IgE, anti-IL5, anti-IL4/13, and anti-TSLP) targeting specific severe asthma phenotypes. While injection is the usual administration route for biologics and vaccines used in asthma, inhalation is an option being explored, although several (mainly formulation) challenges need to be overcome. Other potential novel future inhaled asthma therapies include anti-IL-33/ST2 biologicals and JAK inhibitors, all still requiring more clinical evidence.

Simulation of unsteady flow of SF6gas in a simplified high-voltage circuit breaker model describing the nozzle, contacts and their nearest surrounding is presented. SF6is considered as viscous, compressible, real gas described by Redlich-Kwong model. Heat transfer is taken into account due to the gas compressibility. The heat source, triggered by the electric arc between the contacts, was out of the scope of the current research, thus it was not included in the simulations presented. Turbulence, caused by the gas viscosity, is described using realizable k-εmodel. In the simulation model, one of the contact sides – electrodes, is considered as moving at prescribed velocity. The part of the space ‘swept’ by the moving electrode is considered as the gas with imposed artificially increased viscosity in order to imitate the rigid body behaviour. Thus, no moving parts of the computational mesh are used in the model. The conservation equations of mass, momentum and energy, given in integral form, are solved using a finite-volume method on unstructured computational grids.

Settlement of unintended deviation between scheduled and realized energy exchange among LFC (Load Frequency Control) areas used to be conducted through the energy compensation programs, where energy deviation from period of registration is compensated at a later stage period of compensation of unintended deviation. With the adoption of the Synchronous Area Framework Agreement (SAFA), the Regional Group for Continental Europe the methodology of accounting and financial settlement of unintended deviations FSKAR (Financial settlement k?f, ACE and ramping period) is defined. The FSKAR methodology defines necessary data for the calculation and determination of unintended deviation. The methodology defines the method of determining settlement prices. The paper describes the methodology of determining settlement prices, the method of data collection and validation, the method of calculation of deviations and other energy and financial quantities, and data exchange between entities.

The goal of this project was to create an up‐to‐date joint European clinical practice guideline for the diagnosis and treatment of faecal incontinence (FI), using the best available evidence. These guidelines are intended to help guide all medical professionals treating adult patients with FI (e.g., general practitioners, surgeons, gastroenterologists, other healthcare workers) and any patients who are interested in information regarding the diagnosis and management of FI. These guidelines have been created in cooperation with members from the United European Gastroenterology (UEG), European Society of Coloproctology (ESCP), European Society of Neurogastroenterology and Motility (ESNM) and the European Society for Primary Care Gastroenterology (ESPCG). These members made up the guideline development group (GDG). Additionally, a patient advisory board (PAB) was created to reflect and comment on the draft guidelines from a patient perspective. Relevant review questions were established by the GDG along with a set of outcomes most important for decision making. A systematic literature search was performed using these review questions and outcomes as a framework. For each predefined review question, the study or studies with the highest level of study design were included. If evidence of a higher‐level study design was available, no lower level of evidence was sought or included. Data from the studies were extracted by two reviewers for each predefined important outcome within each review question. Where possible, forest plots were created. After summarising the results for each review question, a systematic quality assessment using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach was performed. For each review question, we assessed the quality of evidence for every predetermined important outcome. After evidence review and quality assessment were completed, recommendations could be formulated. The wording used for each recommendation was dependent on the level of quality of evidence. Lower levels of evidence resulted in weaker recommendations and higher levels of evidence resulted in stronger recommendations. Recommendations were discussed within the GDG to reach consensus. These guidelines contain 45 recommendations on the classification, diagnosis and management of FI in adult patients. These multidisciplinary European guidelines provide an up‐to‐date comprehensive evidence‐based framework with recommendations on the diagnosis and management of adult patients who suffer from FI.

Introduction: Portfolio use to support self-regulated learning (SRL) during clinical workplace learning is widespread, but much is still unknown regarding its effectiveness. This review aimed to gain insight in the extent to which portfolio use supports SRL and under what circumstances. Methods: A realist review was conducted in two phases. First, stakeholder interviews and a scoping search were used to formulate a program theory that explains how portfolio use could support SRL. Second, an in-depth literature search was conducted. The included papers were coded to extract context–mechanism–outcome configurations (CMOs). These were synthesized to answer the research question. Results: Sixteen papers were included (four fulfilled all qualitative rigor criteria). Two primary portfolio mechanisms were established: documenting as a moment of contemplation (learners analyze experiences while writing portfolio reports) and documentation as a reminder of past events (previous portfolio reports aid recall). These mechanisms may explain the positive relationship between portfolio use and self-assessment, reflection, and feedback. However, other SRL outcomes were only supported to a limited extent: formulation of learning objectives and plans, and monitoring. The partial support of the program theory can be explained by interference of contextual factors (e.g., system of assessment) and portfolio-related mechanisms (e.g., mentoring). Discussion: Portfolio research is falling short both theoretically—in defining and conceptualizing SRL—and methodologically. Nevertheless, this review indicates that portfolio use has potential to support SRL. However, the working mechanisms of portfolio use are easily disrupted. These disruptions seem to relate to tensions between different portfolio purposes, which may undermine learners’ motivation.

Introduction: For several decades, educational experts have promoted reflection as essential to professional development. In the medical setting, collaborative reflection has gained significant importance across the curriculum. Collaborative reflection has a unique edge over individual reflection, but many medical teachers find facilitating group reflection sessions challenging and there is little documentation about the didactics of teaching in such collaborative reflection settings. To address this knowledge gap, we aim to capture the professional knowledge base for facilitating collaborative reflection by analyzing the formal and perceived goals and strategies of this practice. Methods: The professional knowledge base consists of formal curricular materials as well as individual teacher expertise. Using Template Analysis, we analyzed the goals and strategies of collaborative reflection reported in institutional training documents and video-stimulated interviews with individual teachers across all Dutch general practitioner training institutes. Results: The analysis resulted in a highly diverse overview of educational goals for residents during the sessions, teacher goals that contribute to those educational goals, and a myriad of situation-specific teacher strategies to accomplish both types of goals. Teachers reported that the main educational goal was for residents to learn and develop and that the teachers’ main goal was to facilitate learning and development by ensuring everyone’s participation in reflection. Key teacher strategies to that end were to manage participation, to ensure a safe learning environment, and to create conditions for learning. Discussion: The variety of strategies and goals that constitute the professional knowledge base for facilitating collaborative reflection in postgraduate medical education shows how diverse and situation-dependent such facilitation can be. Our analysis identifies a repertoire of tools that both novice and experienced teachers can use to develop their professional skill in facilitating collaborative reflection.

Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis. A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements. The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pyloriinfection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pyloristatus should be determined in every patient with dyspeptic symptoms and H. pyloripositive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long‐term prognosis and life expectancy are favorable. A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD. Current knowledge Functional dyspepsia is one of the most common conditions encountered in clinical practice.There is a lack of guidance for clinicians in guiding diagnosis and treatment of this prevalent condition.No treatments are currently approved for the treatment of functional dyspepsia in Europe. Functional dyspepsia is one of the most common conditions encountered in clinical practice. There is a lack of guidance for clinicians in guiding diagnosis and treatment of this prevalent condition. No treatments are currently approved for the treatment of functional dyspepsia in Europe. What is new here A Delphi panel consisting of 41 experts from 22 European countries established the level of consensus on 87 statements regarding functional dyspepsia.The statements reaching consensus serve to guide clinicians in recognizing, diagnosing and treating FD in clinical practice.Endoscopy is mandatory for establishing a firm diagnosis of functional dyspepsia D, but in primary care patients without alarm symptoms or risk factors can be managed without endoscopy.Helicobacter pyloristatus should be determined in every patient with dyspeptic symptoms and H. Pyloripositive patients should receive eradication therapy.Proton pump inhibitor‐therapy is considered an effective therapy for FD, but no other treatment approach reached consensus support. A Delphi panel consisting of 41 experts from 22 European countries established the level of consensus on 87 statements regarding functional dyspepsia. The statements reaching consensus serve to guide clinicians in recognizing, diagnosing and treating FD in clinical practice. Endoscopy is mandatory for establishing a firm diagnosis of functional dyspepsia D, but in primary care patients without alarm symptoms or risk factors can be managed without endoscopy. Helicobacter pyloristatus should be determined in every patient with dyspeptic symptoms and H. Pyloripositive patients should receive eradication therapy. Proton pump inhibitor‐therapy is considered an effective therapy for FD, but no other treatment approach reached consensus support.

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Background An efficient diagnostic pathway and early stage diagnosis for cancer patients is widely pursued. This study aims to chart the duration of the diagnostic pathway for patients with symptomatic oesophageal and gastric cancer, to identify factors associated with long duration and to assess the association of duration with tumour stage at diagnosis.Methods This was a retrospective cohort study, using electronic health records of six routine primary care databases covering about 640,000 patients, partly linked to the Netherlands Cancer Registry. Symptomatic patients with oesophageal and gastric cancer (2010–2015) that presented in primary care were included. Duration of four diagnostic intervals was determined: patient interval; first symptoms to primary care consultation, primary care interval; consultation to referral, secondary care interval; referral to diagnosis, and the diagnostic interval; consultation to diagnosis. Characteristics associated with ‘long duration’ (≥P75 duration) were assessed using log-binomial regression. Median durations were stratified for tumour stages.Results Among 312 symptomatic patients with upper gastrointestinal cancer, median durations were: patient interval: 29 days (interquartile interval 15–73), primary care interval: 12 days (interquartile interval 1–43), secondary care interval: 13 days (interquartile interval 6–29) and diagnostic interval: 31 days (11–74). Patient interval duration was comparable for patients with and without alarm symptoms. Absence of cancer-specific alarm symptoms was associated with ‘long duration’ of primary care interval and secondary care interval: relative risk 5.0 (95% confidence interval 2.7–9.1) and 2.1 (95% confidence interval 1.3–3.7), respectively. Median diagnostic interval duration for local stage disease was 51 days (interquartile interval 13–135) versus 27 days (interquartile interval 11–71) for advanced stage (p= 0.07).Conclusion In the diagnostic pathway of upper gastrointestinal cancers, the longest interval is the patient interval. Reducing time to diagnosis may be achieved by improving patients’ awareness of alarm symptoms and by diagnostic strategies which better identify cancer patients despite low suspicion.

An efficient diagnostic pathway and early stage diagnosis for cancer patients is widely pursued. This study aims to chart the duration of the diagnostic pathway for patients with symptomatic oesophageal and gastric cancer, to identify factors associated with long duration and to assess the association of duration with tumour stage at diagnosis. This was a retrospective cohort study, using electronic health records of six routine primary care databases covering about 640,000 patients, partly linked to the Netherlands Cancer Registry. Symptomatic patients with oesophageal and gastric cancer (2010–2015) that presented in primary care were included. Duration of four diagnostic intervals was determined: patient interval; first symptoms to primary care consultation, primary care interval; consultation to referral, secondary care interval; referral to diagnosis, and the diagnostic interval; consultation to diagnosis. Characteristics associated with ‘long duration’ (=P75 duration) were assessed using log-binomial regression. Median durations were stratified for tumour stages. Among 312 symptomatic patients with upper gastrointestinal cancer, median durations were: patient interval: 29 days (interquartile interval 15–73), primary care interval: 12 days (interquartile interval 1–43), secondary care interval: 13 days (interquartile interval 6–29) and diagnostic interval: 31 days (11–74). Patient interval duration was comparable for patients with and without alarm symptoms. Absence of cancer-specific alarm symptoms was associated with ‘long duration’ of primary care interval and secondary care interval: relative risk 5.0 (95% confidence interval 2.7–9.1) and 2.1 (95% confidence interval 1.3–3.7), respectively. Median diagnostic interval duration for local stage disease was 51 days (interquartile interval 13–135) versus 27 days (interquartile interval 11–71) for advanced stage (p?=?0.07). In the diagnostic pathway of upper gastrointestinal cancers, the longest interval is the patient interval. Reducing time to diagnosis may be achieved by improving patients’ awareness of alarm symptoms and by diagnostic strategies which better identify cancer patients despite low suspicion.

The majority of past studies assessed the impact of oil price on stock returns using aggregate stock price index from different countries and assuming the effects to be symmetric. In this paper, we investigate asymmetric causality not only from oil price to stock returns but also from stock returns to oil price. To reduce aggregation bias, we use data from nine different sectors of the U.S. economy. We found that an increase in oil price causes returns of three sectors, while a decrease in oil price causes returns of four sectors, all in the short run. On the other hand, we found that an increase in returns in three sectors causes oil price to rise, while a decrease in returns in six sectors causes oil price to decline. We do not discover significant long-run causal relationship in either direction.

Children are often viewed as poor eyewitnesses. Fact-finders, lawyers, and researchers assume that children are exceptionally prone to accept external suggestive (leading) questions and to create false memories. Is this assumption justified? This review will show it is not. First, studies on spontaneous false memories—elicited without any suggestive pressure—reveal that children are less likely than adults to produce them. Second, under certain circumstances, children are even less prone to accept external suggestions than adults. This counterintuitive finding happens when false suggestions contain information that is associatively related but in actuality not experienced by children or adults. Using empirically based interview protocols can maximize the retrieval of accurate memories in children and adults. Furthermore, expert witnesses should use alternative scenarios to better evaluate whether statements by children or adults are based on truth or fiction.

We recently made the case that associative activation is a viable mechanism underlying false memory formation and hence also false memory formation in psychopathology. In a recent issue of Clinical Psychological Science, Tryon argued that our description of associative activation did not meet the criteria of causation and explanatory value in order to qualify as a mechanism. In this commentary, we explain why we disagree with Tryon. Many studies focused on associative activation and false memory creation. We believe that these studies provide good arguments for associative activation as a likely causal antecedent in the production of false memories.

We analyze the downlink of a massive multiuser multiple input, multiple output (MIMO) system where antenna units at the base station are connected in a daisy chain without a central processing unit and only possess local channel knowledge. For this setup, we develop and analyze a linear precoding algorithm for suppressing interuser interference. It is demonstrated that the algorithm is close to zero-forcing precoding in terms of performance for a large number of antennas. Moreover, we show that with careful scheduling of processing across antennas, requirements for interconnection throughput are reduced compared with the fully centralized solution. Favorable tradeoff between performance and interconnection throughput makes the daisy chain a viable candidate topology for real-life implementations of base stations in MIMO systems where the number of antennas is very large.

In clinical and court settings, it is imperative to know whether posttraumatic stress disorder (PTSD) and depression may make people susceptible to false memories. We conducted a review of the literature on false memory effects in participants with PTSD, a history of trauma, or depression. When emotional associative material was presented to these groups, their levels of false memory were raised relative to those in relevant comparison groups. This difference did not consistently emerge when neutral or nonassociative material was presented. Our conclusion is supported by a quantitative comparison of effect sizes between studies using emotional associative or neutral, nonassociative material. Our review suggests that individuals with PTSD, a history of trauma, or depression are at risk for producing false memories when they are exposed to information that is related to their knowledge base.

Dans les lettres dites « du voyant », Rimbaud se donne comme tâche de « trouver une langue » engageant une réflexion sur ce qu'est la langue de création qui s'accompagne dans sa poésie d'une interrogation sur la qualité du matériau poétique qu'est le langage et sur sa forme: celle de la prose. Trouver une langue pour faire de la poésie c'est trouver la forme d'une parole polyphonique et presque polyglotte. Le « je est un autre » de Rimbaud résonne avec la formule de Derrida « Je n'ai qu'une langue mais ce n'est pas la mienne » pour la transformer en: « Je n'est qu'une langue, mais ce n'est pas moi. » La poésie rimbaldienne se définit comme un projet où le je est à la fois multiple et potentiel pour devenir ce « lieu mixte » dont parle Kristin Ross et mettre au point ce que nous appellerons une éthique de la traduction.

Resident loved ones of patients with COPD can play an important role in helping these patients engage in physical activity. We aimed to compare activity levels and exercise motivation between patients with COPD and their resident loved ones; to compare the same outcome measures in patients after stratification for the physical activity level of the loved ones; and to predict the likelihood of being physically active in patients with a physically active resident loved one.

L’infiltration des eaux pluviales urbaines dans les nappes est une technique alternative au système traditionnel d’assainissement largement utilisée dans l’Est lyonnais. Les eaux infiltrées conduisent à l’accumulation dans les premiers centimètres du sol de matière organique, de polluants organiques et minéraux et de micro-organismes. Ce papier présente les différents travaux menés pour mieux comprendre le rôle du compartiment microbien de cette surface sur le devenir des métaux piégés à la surface et le risque de leur migration dans la nappe souterraine. Une approche sur métal et bactérie modèles a permis de mettre en évidence une forte capacité d’adsorption des cations métalliques par la bactérie, adsorption qui peut conduire au transfert de ce métal via le transport biocolloïdal. Des études sur milieu réels multicontaminés montre que les bactéries présentes en grands nombres dans ces milieux pollués sont adaptées à ce stress chimique et sont potentiellement très actives.

Context and Objective:Moderate-to-vigorous physical activity (MVPA) and physical fitness (PF) are positively associated with glucose tolerance. Such associations may be partly conditioned by microvascular function, which is a common correlate to MVPA, PF, and glucose tolerance. To test this hypothesis, the present study sought to investigate independent associations of MVPA and PF with glucose tolerance and to what extent these associations are mediated by microvascular function.Design, Setting, Participants, and Outcome Measures:Data from The Maastricht Study were used (n = 512 for MVPA and n = 488 for PF analyses; mean age, 59 [SD = 9] y, 52 % men). Glucose tolerance was assessed by 2-hour postload plasma glucose levels (2hPG). The total number of weekly hours of MVPA was estimated with the Community Healthy Activities Model Program for Seniors questionnaire. Walking speed during the 6-minute walk test was used to evaluate PF. Microvascular function was determined by postocclusive capillary recruitment and flowmotion with capillaroscopy and laser Doppler flowmetry in skin microcirculation.Results:In univariate analyses, MVPA, PF, and microvascular function variables were associated with 2hPG. MVPA (n = 512, β = −0.056, P= .019) and PF (n = 488, β = −0.368, P= .006) remained associated with 2hPG after adjustment for established cardio-metabolic risk factors and history of cardiovascular disease; addition of microvascular function variables as potential mediators did not materially change the associations of MVPA (β = −0.054, P= .024) and PF (β = −0.364, P= .006) with 2hPG. No mediation effects of microvascular function variables were detected.Conclusions:MVPA and PF were independently associated with 2hPG, irrespective of established risk factors and generalized microvascular function. The possibility that specific microvascular functions, eg, insulin-mediated vasodilation, influence the association of MVPA and PF with 2hPG needs further investigation.

This study examines the ability of nanozeolite-geopolyme ras adsorbent material for motor vehicle emissions. There were three samples that have been synthesized by varying metakaolin and rice husk ash masses. Nanozeolite-geopolymer samples were synthesized through geopolymerization method at 70°C by mixing metakaolin with rice husk ash and activated with NaOH solution. Samples were recurring at 200°C to improve the crystalline level. Based on the XRD characterization of the three samples, two of them contain zeolite X, namely ZG_A (100% metakaolin, ASP 0%) and ZG_B (metakaolin: ASP, 2: 1). However, zeolite X phase most conceived by ZG_A. Therefore, the ZG_A sample was then used as adsorbent to absorb motor vehicle exhaust. The tests were performed four times with time variation of 10, 20, 30, and 40 minutes. The XRD results showed that the material was successfully absorbed lead oxide, manganese oxide and phosphorus which are hazardous compounds when inhale by human being.

This paper investigates to what extent international migration can be explained by climatic variations. A gravity model of migration augmented with average temperature and precipitation in the country of origin is estimated using a panel data set of 142 sending countries for the period 1995 to 2006. We find two primary results. First, temperature is positively correlated with migration. Second, stronger changes in precipitation are also associated with aligned, but small changes in migration. Both effects are robust to various model modifications. Furthermore, we present initial explorations into the channels relating climate changes with migration via agriculture and internal conflict. F22, Q54

Growth cone guidance is driven by attractive and repulsive signaling cues. Until recently, repulsive signaling by semaphorins was thought to be mediated through Plexin receptors, whereas Slits-induced repulsion was solely mediated through Robo receptors. In a recent report published in Nature Neuroscience, Celine Delloye-Bourgeois and colleagues (2015) combined phenotypic analyses of transgenic mouse lines and in vitrobiochemical experiments to identify PlexinA1 as a novel receptor for Slits. Strikingly, they uncovered for the very first time that the Slit2C-terminal fragment possesses some unique biological activity as binding partner for PlexinA1. Even more excitingly, the signaling cascade triggered by SlitC binding to PlexinA1 mediates growth cone collapse of commissural axons both in vivoand ex vivoand nicely complements Robo-Slit signaling in the developing spinal cord midline to prevent midline recrossing.

Penile cancer is rare among male malignancies. Various biomarkers have been used to predict the prognosis of cancer, one of which is the neutrophil to lymphocyte ratio (NLR). Therefore, we conducted this systematic review and meta-analysis to evaluate the prognostic value of NLR in penile cancer.

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