Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) Consensus Task Force recommendations for evaluation and management.

OBJECTIVE: To develop disease-specific recommendations for the diagnosis and management of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) (EGPA). METHODS: The EGPA Consensus Task Force experts comprised 8 pulmonologists, 6 internists, 4 rheumatologists, 3 nephrologists, 1 pathologist and 1 allergist from 5 European countries and the USA. Using a modified Delphi process, a list of 40 questions was elaborated by 2 members and sent to all participants prior to the meeting. Concurrently, an extensive literature search was undertaken with publications assigned with a level of evidence according to accepted criteria. Drafts of the recommendations were circulated for review to all members until final consensus was reached. RESULTS: Twenty-two recommendations concerning the diagnosis, initial evaluation, treatment and monitoring of EGPA patients were established. The relevant published information on EGPA, antineutrophil-cytoplasm antibody-associated vasculitides, hypereosinophilic syndromes and eosinophilic asthma supporting these recommendations was also reviewed. DISCUSSION: These recommendations aim to give physicians tools for effective and individual management of EGPA patients, and to provide guidance for further targeted research.

New Insights in the Diagnosis and Treatment of Heart Failure.

Cardiovascular disease is the leading cause of mortality in the US and in westernized countries with ischemic heart disease accounting for the majority of these deaths. Paradoxically, the improvements in the medical and surgical treatments of acute coronary syndrome are leading to an increasing number of "survivors" who are then developing heart failure. Despite considerable advances in its management, the gold standard for the treatment of end-stage heart failure patients remains heart transplantation. Nevertheless, this procedure can be offered only to a small percentage of patients who could benefit from a new heart due to the limited availability of donor organs. The aim of this review is to evaluate the safety and efficacy of innovative approaches in the diagnosis and treatment of patients refractory to standard medical therapy and excluded from cardiac transplantation lists.

Epilepsy priorities in Europe: A report of the ILAE-IBE Epilepsy Advocacy Europe Task Force.

The European Forum on Epilepsy Research (ERF2013), which took place in Dublin, Ireland, on May 26-29, 2013, was designed to appraise epilepsy research priorities in Europe through consultation with clinical and basic scientists as well as representatives of lay organizations and health care providers. The ultimate goal was to provide a platform to improve the lives of persons with epilepsy by influencing the political agenda of the EU. The Forum highlighted the epidemiologic, medical, and social importance of epilepsy in Europe, and addressed three separate but closely related concepts. First, possibilities were explored as to how the stigma and social burden associated with epilepsy could be reduced through targeted initiatives at EU national and regional levels. Second, ways to ensure optimal standards of care throughout Europe were specifically discussed. Finally, a need for further funding in epilepsy research within the European Horizon 2020 funding programme was communicated to politicians and policymakers participating to the forum. Research topics discussed specifically included (1) epilepsy in the developing brain; (2) novel targets for innovative diagnostics and treatment of epilepsy; (3) what is required for prevention and cure of epilepsy; and (4) epilepsy and comorbidities, with a special focus on aging and mental health. This report provides a summary of recommendations that emerged at ERF2013 about how to (1) strengthen epilepsy research, (2) reduce the treatment gap, and (3) reduce the burden and stigma associated with epilepsy. Half of the 6 million European citizens with epilepsy feel stigmatized and experience social exclusion, stressing the need for funding trans-European awareness campaigns and monitoring their impact on stigma, in line with the global commitment of the European Commission and with the recommendations made in the 2011 Written Declaration on Epilepsy. Epilepsy care has high rates of misdiagnosis and considerable variability in organization and quality across European countries, translating into huge societal cost (0.2% GDP) and stressing the need for cost-effective programs of harmonization and optimization of epilepsy care throughout Europe. There is currently no cure or prevention for epilepsy, and 30% of affected persons are not controlled by current treatments, stressing the need for pursuing research efforts in the field within Horizon 2020. Priorities should include (1) development of innovative biomarkers and therapeutic targets and strategies, from gene and cell-based therapies to technologically advanced surgical treatment; (2) addressing issues raised by pediatric and aging populations, as well as by specific etiologies and comorbidities such as traumatic brain injury (TBI) and cognitive dysfunction, toward more personalized medicine and prevention; and (3) translational studies and clinical trials built upon well-established European consortia.

Soldiers in a stingless bee: work rate and task repertoire suggest they are an elite force

The differentiation of workers into morphological subcastes (e.g., soldiers) represents an important evolutionary transition and is thought to improve division of labor in social insects. Soldiers occur in many ant and termite species, where they make up a small proportion of the workforce. A common assumption of worker caste evolution is that soldiers are behavioral specialists. Here, we report the first test of the "rare specialist" hypothesis in a eusocial bee. Colonies of the stingless bee Tetragonisca angustula are defended by a small group of morphologically differentiated soldiers. Contrary to the rare specialist hypothesis, we found that soldiers worked more (+34%-41%) and performed a greater variety of tasks (+23%-34%) than other workers, particularly early in life. Our results suggest a "rare elite" function of soldiers in T. angustula, that is, that they perform a disproportionately large amount of the work. Division of labor was based on a combination of temporal and physical castes, but soldiers transitioned faster from one task to the next. We discuss why the rare specialist assumption might not hold in species with a moderate degree of worker differentiation.

Language Learning in Task Management and Task Accomplishment

In this paper we study student interaction in English and Swedish courses at a Finnish university. We focus on language choices made in task-related activities in small group interaction. Our research interests arose from the change in the teaching curriculum, in which content and language courses were integrated at Tampere University of Technology in 2013. Using conversation analysis, we analysed groups of 4-5 students who worked collaboratively on a task via a video conference programme. The results show how language alternation has different functions in 1) situations where students orient to managing the task, e.g., in transitions into task, or where they orient to technical problems, and 2) situations where students accomplish the task. With the results, we aim to show how language alternation can provide interactional opportunities for language learning. The findings will be useful in designing tasks in the future.

Anthropomorphic model observer performance in three-dimensional detection task for low-contrast computed tomography.

X-ray medical imaging is increasingly becoming three-dimensional (3-D). The dose to the population and its management are of special concern in computed tomography (CT). Task-based methods with model observers to assess the dose-image quality trade-off are promising tools, but they still need to be validated for real volumetric images. The purpose of the present work is to evaluate anthropomorphic model observers in 3-D detection tasks for low-contrast CT images. We scanned a low-contrast phantom containing four types of signals at three dose levels and used two reconstruction algorithms. We implemented a multislice model observer based on the channelized Hotelling observer (msCHO) with anthropomorphic channels and investigated different internal noise methods. We found a good correlation for all tested model observers. These results suggest that the msCHO can be used as a relevant task-based method to evaluate low-contrast detection for CT and optimize scan protocols to lower dose in an efficient way.

Cost-effectiveness analysis of cardiac resynchronization therapy in patients with NYHA I and NYHA II heart failure in Spain

Objectives: The aim of the study was to combine clinical results from the European Cohort of the REVERSE study and costs associated with the addition of cardiac resynchronization therapy (CRT) to optimal medical therapy (OMT) in patients with mild symptomatic (NYHA I-II) or asymptomatic left ventricular dysfunction and markers of cardiac dyssynchrony in Spain. Methods: A Markov model was developed with CRT + OMT (CRT-ON) versus OMT only (CRT-OFF) based on a retrospective cost-effectiveness analysis. Raw data was derived from literature and expert opinion, reflecting clinical and economic consequences of patient"s management in Spain. Time horizon was 10 years. Both costs (euro 2010) and effects were discounted at 3 percent per annum. Results: CRT-ON showed higher total costs than CRT-OFF; however, CRT reduced the length of hospitalization in ICU by 94 percent (0.006 versus 0.091 days) and general ward in by 34 percent (0.705 versus 1.076 days). Surviving CRT-ON patients (88.2 percent versus 77.5 percent) remained in better functional class longer, and they achieved an improvement of 0.9 life years (LYGs) and 0.77 years quality-adjusted life years (QALYs). CRT-ON proved to be cost-effective after 6 years, except for the 7th year due to battery depletion. At 10 years, the results were 18,431 per LYG and 21,500 per QALY gained. Probabilistic sensitivity analysis showed CRT-ON was cost-effective in 75.4 percent of the cases at 10 years. Conclusions: The use of CRT added to OMT represents an efficient use of resources in patients suffering from heart failure in NYHA functional classes I and II.

Prognostic Importance of the Cuse of Renal Failure in Patients With Cirrhosis

BACKGROUND & AIMS: The prognostic value of the different causes of renal failure in cirrhosis is not well established. This study investigated the predictive value of the cause of renal failure in cirrhosis. METHODS: Five hundred sixty-two consecutive patients with cirrhosis and renal failure (as defined by serum creatinine 1.5 mg/dL on 2 successive determinations within 48 hours) hospitalized over a 6-year period in a single institution were included in a prospective study. The cause of renal failure was classified into 4 groups: renal failure associated with bacterial infections, renal failure associated with volume depletion, hepatorenal syndrome (HRS), and parenchymal nephropathy. The primary end point was survival at 3 months. RESULTS: Four hundred sixty-three patients (82.4%) had renal failure that could be classified in 1 of 4 groups. The most frequent was renal failure associated with infections (213 cases; 46%), followed by hypovolemia-associated renal failure (149; 32%), HRS (60; 13%), and parenchymal nephropathy (41; 9%). The remaining patients had a combination of causes or miscellaneous conditions. Prognosis was markedly different according to cause of renal failure, 3-month probability of survival being 73% for parenchymal nephropathy, 46% for hypovolemia-associated renal failure, 31% for renal failure associated with infections, and 15% for HRS (P .0005). In a multivariate analysis adjusted for potentially confounding variables, cause of renal failure was independently associated with prognosis, together with MELD score, serum sodium, and hepatic encephalopathy at time of diagnosis of renal failure. CONCLUSIONS: A simple classification of patients with cirrhosis according to cause of renal failure is useful in assessment of prognosis and may help in decision making in liver transplantation.

Accessing forgotten memory traces from long-term memory via visual movements

Because memory retrieval often requires overt responses, it is difficult to determine to what extend forgetting occurs as a problem in explicit accessing of long-term memory traces. In this study, we used eye-tracking measures in combination with a behavioural task that favoured high forgetting rates to investigate the existence of memory traces from long-term memory in spite of failure in accessing them consciously. In 2 experiments, participants were encouraged to encode a large set of sound-picture56 location associations. In a later test, sounds were presented and participants were instructed to visually scan, before a verbal memory report, for the correct location of the associated pictures in an empty screen. We found the reactivation of associated memories by sound cues at test biased oculomotor behaviour towards locations congruent with memory representations, even when participants failed to consciously provide a memory report of it. These findings reveal the emergence of a memory-guided behaviour that can be used to map internal representations of forgotten memories from long-term memory.

Définition et prise en charge de l'échec d'une première injection de toxine botulique Botox(®) 200 U pour hyperactivité détrusorienne neurogène : résultats de l'enquête DETOX [Definition of botulinum toxin failure in neurogenic detrusor overactivity: Preliminary results of the DETOX survey].

OBJECTIVE: There is currently no guideline regarding the management of neurogenic detrusor overactivity (NDO) refractory to intra-detrusor botulinum toxin injections. The primary objective of the present study was to find a consensus definition of failure of botulinum toxin intra-detrusor injections for NDO. The secondary objective was to report current trends in the managment of NDO refractory to botulinum toxin. METHODS: A survey was created, based on data drawn from current literature, and sent via e-mail to all the experts form the Group for research in neurourology in french language (GENULF) and from the comittee of neurourology of the French urological association (AFU). The experts who did not answer to the first e-mail were contacted again twice. Main results from the survey are presented and expressed as numbers and proportions. RESULTS: Out of the 42 experts contacted, 21 responded to the survey. Nineteen participants considered that the definition of failure should be a combination of clinical and urodynamics criteria. Among the urodynamics criteria, the persistence of a maximum detrusor pressure>40cm H2O was the most supported by the experts (18/21, 85%). According to the vast majority of participants (19/21, 90.5%), the impact of injections on urinary incontinence should be included in the definition of failure. Regarding the management, most experts considered that the first line treatment in case of failure of a first intra-detrusor injection of Botox(®) 200 U should be a repeat injection of Botox(®) at a higher dosage (300 U) (15/20, 75%), regardless of the presence or not of urodynamics risk factors of upper tract damage (16/20, 80%). CONCLUSION: This work has provided a first overview of the definition of failure of intra-detrusor injections of botulinum toxin in the management of NDO. For 90.5% of the experts involved, the definition of failure should be clinical and urodynamic and most participants (75%) considered that, in case of failure of a first injection of Botox(®) 200 U, repeat injection of Botox(®) 300 U should be the first line treatment. Level of proof 4.

Presence of Leishmania RNA Virus 1 in Leishmania guyanensis Increases the Risk of First-Line Treatment Failure and Symptomatic Relapse.

Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (TL). Such complications are seen frequently in Leishmania guyanensis infections, in which patients respond variously to first-line antileishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently, we reported that a double-stranded RNA virus, Leishmania RNA virus 1 (LRV1), nested within L. guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyperinflammatory response. This report investigates the prevalence of LRV1 in human L. guyanensis infection and its effect on treatment efficacy, as well as its correlation to symptomatic relapses after the completion of first-line treatment. In our cohort of 75 patients with a diagnosis of primary localized American TL, the prevalence of LRV1-positive L. guyanensis infection was elevated to 58%. All patients infected with LRV1-negative L. guyanensis were cured after 1 dose (22 of 31 [71%]) or 2 doses (31 of 31 [100%]) of pentamidine. In contrast, 12 of 44 LRV1-positive patients (27%) presented with persistent infection and symptomatic relapse that required extended therapy and the use of second-line drugs. Finally, LRV1 presence was associated with a significant increase in levels of intra-lesional inflammatory markers. In conclusion, LRV1 status in L. guyanensis infection is significantly predictive (P = .0009) of first-line treatment failure and symptomatic relapse and has the potential to guide therapeutic choices in American TL.

Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVES: Sudden cardiac death (SCD) is a severe burden of modern medicine. Aldosterone antagonist is publicized as effective in reducing mortality in patients with heart failure (HF) or post myocardial infarction (MI). Our study aimed to assess the efficacy of AAs on mortality including SCD, hospitalization admission and several common adverse effects. METHODS: We searched Embase, PubMed, Web of Science, Cochrane library and clinicaltrial.gov for randomized controlled trials (RCTs) assigning AAs in patients with HF or post MI through May 2015. The comparator included standard medication or placebo, or both. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Event rates were compared using a random effects model. Prospective RCTs of AAs with durations of at least 8 weeks were selected if they included at least one of the following outcomes: SCD, all-cause/cardiovascular mortality, all-cause/cardiovascular hospitalization and common side effects (hyperkalemia, renal function degradation and gynecomastia). RESULTS: Data from 19,333 patients enrolled in 25 trials were included. In patients with HF, this treatment significantly reduced the risk of SCD by 19% (RR 0.81; 95% CI, 0.67-0.98; p = 0.03); all-cause mortality by 19% (RR 0.81; 95% CI, 0.74-0.88, p<0.00001) and cardiovascular death by 21% (RR 0.79; 95% CI, 0.70-0.89, p<0.00001). In patients with post-MI, the matching reduced risks were 20% (RR 0.80; 95% CI, 0.66-0.98; p = 0.03), 15% (RR 0.85; 95% CI, 0.76-0.95, p = 0.003) and 17% (RR 0.83; 95% CI, 0.74-0.94, p = 0.003), respectively. Concerning both subgroups, the relative risks respectively decreased by 19% (RR 0.81; 95% CI, 0.71-0.92; p = 0.002) for SCD, 18% (RR 0.82; 95% CI, 0.77-0.88, p < 0.0001) for all-cause mortality and 20% (RR 0.80; 95% CI, 0.74-0.87, p < 0.0001) for cardiovascular mortality in patients treated with AAs. As well, hospitalizations were significantly reduced, while common adverse effects were significantly increased. CONCLUSION: Aldosterone antagonists appear to be effective in reducing SCD and other mortality events, compared with placebo or standard medication in patients with HF and/or after a MI.

The First International Workshop on Warning Criteria for Active Slides: technical issues, problems and solutions for managing early warning systems

Early warning systems (EWSs) rely on the capacity to forecast a dangerous event with a certain amount of advance by defining warning criteria on which the safety of the population will depend. Monitoring of landslides is facilitated by new technologies, decreasing prices and easier data processing. At the same time, predicting the onset of a rapid failure or the sudden transition from slow to rapid failure and subsequent collapse, and its consequences is challenging for scientists that must deal with uncertainties and have limited tools to do so. Furthermore, EWS and warning criteria are becoming more and more a subject of concern between technical experts, researchers, stakeholders and decision makers responsible for the activation, enforcement and approval of civil protection actions. EWSs imply also a sharing of responsibilities which is often averted by technical staff, managers of technical offices and governing institutions. We organized the First International Workshop on Warning Criteria for Active Slides (IWWCAS) to promote sharing and networking among members from specialized institutions and relevant experts of EWS. In this paper, we summarize the event to stimulate discussion and collaboration between organizations dealing with the complex task of managing hazard and risk related to active slides.

A Hierarchical Approach for Multi-task Logistic Regression

Peer-reviewed