Actigraphic assessment of periodic leg movements in patients with restless legs syndrome.

The diagnosis of restless legs syndrome (RLS) relies upon diagnostic criteria which are based on history only, and dopaminergic treatment is not normally the first choice of treatment for all patients. It would be worthwhile to identify patients non-responsive to dopaminergic treatment beforehand, because they may suffer from a restless legs-like syndrome and may require alternative treatment. We included retrospectively 24 adult patients fulfilling the four essential criteria for restless legs and 12 age-matched healthy controls. They were investigated by ambulatory actigraphy from both legs over three nights, and patients started treatment with dopamine agonists after this diagnostic work-up. We examined 12 responders to dopaminergic treatment and 12 non-responders and studied the association between response to dopaminergic treatment and the periodic limb movement index (PLMI) as assessed with actigraphy. Demographic characteristics, excessive daytime sleepiness and fatigue at baseline were similar in all three groups. Baseline RLS severity was similar between responders and non-responders [International Restless Legs Severity Scale (IRLS): 25 ± 9 and 24 ± 8]. Group comparisons of PLMI before treatment initiation showed significant differences between the three groups. Post-hoc pairwise comparisons revealed that healthy controls had significantly lower PLMI (4.9 ± 4.5) than responders (29.3 ± 22.7) and non-responders (13.3 ± 11.2). Similarly, the PLMI in responders was lower than in non-responders. PLMI day-to-day variability did not differ between responders and non-responders and there was no correlation between treatment effect, as assessed by the decrease of the IRLS and baseline PLMI. Our retrospective study indicates that actigraphy to assess periodic limb movements may contribute to a better diagnosis of dopamine-responsive restless legs syndrome.

Theoretical framework for the assessment of vulnerability to natural hazards and climate change [in Europe]

Reducing risk that emerges from hazards of natural origin and societal vulnerability is a key challenge for the development of more resilient communities and the overall goal of sustainable development. The following chapter outlines a framework for multidimensional, holistic vulnerability assessment that is understood as part of risk evaluation and risk management in the context of Disaster Risk Management (DRM) and Climate Change Adaptation (CCA). As a heuristic, the framework is a thinking tool to guide systematic assessments of vulnerability and to provide a basis for comparative indicators and criteria development to assess key factors and various dimensions of vulnerability, particularly in regions in Europe, however, it can also be applied in other world regions. The framework has been developed within the context of the research project MOVE (Methods for the Improvement of Vulnerability Assessment in Europe; ) sponsored by the European Commission within the framework of the FP 7 program.

Image-based biomechanical assessment of vertebral body and intervertebral disc in the human lumbar spine

Life expectancy continuously increases but our society faces age-related conditions. Among musculoskeletal diseases, osteoporosis associated with risk of vertebral fracture and degenerative intervertebral disc (IVD) are painful pathologies responsible for tremendous healthcare costs. Hence, reliable diagnostic tools are necessary to plan a treatment or follow up its efficacy. Yet, radiographic and MRI techniques, respectively clinical standards for evaluation of bone strength and IVD degeneration, are unspecific and not objective. Increasingly used in biomedical engineering, CT-based finite element (FE) models constitute the state-of-art for vertebral strength prediction. However, as non-invasive biomechanical evaluation and personalised FE models of the IVD are not available, rigid boundary conditions (BCs) are applied on the FE models to avoid uncertainties of disc degeneration that might bias the predictions. Moreover, considering the impact of low back pain, the biomechanical status of the IVD is needed as a criterion for early disc degeneration. Thus, the first FE study focuses on two rigid BCs applied on the vertebral bodies during compression test of cadaver vertebral bodies, vertebral sections and PMMA embedding. The second FE study highlights the large influence of the intervertebral disc’s compliance on the vertebral strength, damage distribution and its initiation. The third study introduces a new protocol for normalisation of the IVD stiffness in compression, torsion and bending using MRI-based data to account for its morphology. In the last study, a new criterion (Otsu threshold) for disc degeneration based on quantitative MRI data (axial T2 map) is proposed. The results show that vertebral strength and damage distribution computed with rigid BCs are identical. Yet, large discrepancies in strength and damage localisation were observed when the vertebral bodies were loaded via IVDs. The normalisation protocol attenuated the effect of geometry on the IVD stiffnesses without complete suppression. Finally, the Otsu threshold computed in the posterior part of annulus fibrosus was related to the disc biomechanics and meet objectivity and simplicity required for a clinical application. In conclusion, the stiffness normalisation protocol necessary for consistent IVD comparisons and the relation found between degeneration, mechanical response of the IVD and Otsu threshold lead the way for non-invasive evaluation biomechanical status of the IVD. As the FE prediction of vertebral strength is largely influenced by the IVD conditions, this data could also improve the future FE models of osteoporotic vertebra.

Assessment of low-flow, low-gradient, severe aortic stenosis: an invasive evaluation is required for decision making.

Low-flow, low-gradient severe aortic stenosis (AS) is characterised by a small aortic valve area (AVA) and low mean gradient (MG) secondary to a low cardiac output and may occur in patients with either a preserved or reduced left ventricular ejection fraction (LVEF). Symptomatic patients presenting with low-flow, low-gradient severe AS have a dismal prognosis independent of baseline LVEF if managed conservatively and should therefore undergo aortic valve replacement if feasible. Transthoracic echocardiography (TTE) is the first-line investigation for the assessment of AS haemodynamic severity. However, when confronted with guideline-discordant AVA (small) and MG (low) values, there are several reasons other than severe AS combined with a low cardiac output which may lead to such a situation, including erroneous measurements, small body size, inherent inconsistencies in the guidelines' criteria, prolonged ejection time and aortic pseudostenosis. The distinction between these various entities poses a diagnostic challenge. However, it is important to make a distinction because each has very different implications in terms of risk stratification and therapeutic management. In such instances, cardiac catheterisation forms an integral part of the work-up of these patients in order to confirm or refute the echocardiographic findings to guide management decisions appropriately.

Defined morphological criteria allow reliable diagnosis of colorectal serrated polyps and predict polyp genetics.

Criteria for the diagnosis of serrated colorectal lesions (hyperplastic polyp, sessile serrated adenoma without or with dysplasia--which we called mixed polyp--and traditional serrated adenoma) for which consensus has been reached should be validated for applicability in daily practice in terms of inter-observer reproducibility and their association with clinical features and (epi)genetic events. A study set was created from a consecutive series of colorectal polyps (n = 1,926) by selecting all sessile serrated adenomas, traditional serrated adenomas and mixed polyps. We added consecutive series of hyperplastic polyps, classical adenomas and normal mucosa samples for a total of 200 specimens. With this series, we conducted an inter-observer study, encompassing ten pathologists with gastrointestinal pathology experience from five European countries, in three rounds in which all cases were microscopically evaluated. An assessment of single morphological criteria was included, and these were correlated with clinical parameters and the mutation status of KRAS, BRAF and PIK3CA and the methylation status of MLH1. Gender, age and localisation were significantly associated with certain types of lesions. Kappa statistics revealed moderate to good inter-observer agreement for polyp classification (κ = 0.56 to 0.63), but for single criteria, this varied considerably (κ = 0.06 to 0.82). BRAF mutations were frequently found in hyperplastic polyps (86 %, 62/72) and sessile serrated adenomas (80 %, 41/51). KRAS mutations occurred more frequently in traditional serrated adenomas (78 %, 7/9) and less so in classical adenomas (20 %, 10/51). Single morphological criteria for sessile serrated adenomas showed significant correlation with BRAF mutation (all p ≤ 0.001), and those for classical adenomas or traditional serrated adenoma correlated significantly with KRAS mutation (all p < 0.001). Therefore, single well-defined morphological criteria are predictive for genetic alterations in colorectal polyps.

Quality control for retinal OCT in multiple sclerosis: validation of the OSCAR-IB criteria.

BACKGROUND Retinal optical coherence tomography (OCT) permits quantification of retinal layer atrophy relevant to assessment of neurodegeneration in multiple sclerosis (MS). Measurement artefacts may limit the use of OCT to MS research. OBJECTIVE An expert task force convened with the aim to provide guidance on the use of validated quality control (QC) criteria for the use of OCT in MS research and clinical trials. METHODS A prospective multi-centre (n = 13) study. Peripapillary ring scan QC rating of an OCT training set (n = 50) was followed by a test set (n = 50). Inter-rater agreement was calculated using kappa statistics. Results were discussed at a round table after the assessment had taken place. RESULTS The inter-rater QC agreement was substantial (kappa = 0.7). Disagreement was found highest for judging signal strength (kappa = 0.40). Future steps to resolve these issues were discussed. CONCLUSION Substantial agreement for QC assessment was achieved with aid of the OSCAR-IB criteria. The task force has developed a website for free online training and QC certification. The criteria may prove useful for future research and trials in MS using OCT as a secondary outcome measure in a multi-centre setting.

Approaches to Ensure Quality Standards for Standardized/ Simulated Patient Performance in High Stakes Objective Structured Clinical Exams (OSCEs)

Introduction To meet the quality standards for high-stakes OSCEs, it is necessary to ensure high quality standardized performance of the SPs involved.[1] One of the ways this can be assured is through the assessment of the quality of SPs` performance in training and during the assessment. There is some literature concerning validated instruments that have been used to assess SP performance in formative contexts but very little related to high stakes contexts.[2], [3], [4]. Content and structure During this workshop different approaches to quality control for SPs` performance, developed in medicine, pharmacy and nursing OSCEs, will be introduced. Participants will have the opportunity to use these approaches in simulated interactions. Advantages and disadvantages of these approaches will be discussed. Anticipated outcomes By the end of this session, participants will be able to discuss the rationale for quality control of SPs` performance in high stakes OSCEs, outline key factors in creating strategies for quality control, identify various strategies for assuring quality control, and reflect on applications to their own practice. Who should attend The workshop is designed for those interested in quality assurance of SP performance in high stakes OSCEs. Level All levels are welcome. References Adamo G. 2003. Simulated and standardized patients in OSCEs: achievements and challenges:1992-2003. Med Teach. 25(3), 262- 270. Wind LA, Van Dalen J, Muijtjens AM, Rethans JJ. Assessing simulated patients in an educational setting: the MaSP (Maastricht Assessment of Simulated Patients). Med Educ 2004, 38(1):39-44. Bouter S, van Weel-Baumgarten E, Bolhuis S. Construction and validation of the Nijmegen Evaluation of the Simulated Patient (NESP): Assessing Simulated Patients' ability to role-play and provide feedback to students. Acad Med: Journal of the Association of American Medical Colleges 2012. May W, Fisher D, Souder D: Development of an instrument to measure the quality of standardized/simulated patient verbal feedback. Med Educ 2012, 2(1).

Law and science: risk assessment and risk management in the WTO agreement on the application of sanitary and phytosanitary measures

Assessing and managing risks relating to the consumption of food stuffs for humans and to the environment has been one of the most complex legal issues in WTO law, ever since the Agreement on Sanitary and Phytosanitary Measures was adopted at the end of the Uruguay Round and entered into force in 1995. The problem was expounded in a number of cases. Panels and the Appellate Body adopted different philosophies in interpreting the agreement and the basic concept of risk assessment as defined in Annex A para. 4 of the Agreement. Risk assessment entails fundamental question on law and science. Different interpretations reflect different underlying perceptions of science and its relationship to the law. The present thesis supported by the Swiss National Research Foundation undertakes an in-depth analysis of these underlying perceptions. The author expounds the essence and differences of positivism and relativism in philosophy and natural sciences. He clarifies the relationship of fundamental concepts such as risk, hazards and probability. This investigation is a remarkable effort on the part of lawyer keen to learn more about the fundamentals based upon which the law – often unconsciously – is operated by the legal profession and the trade community. Based upon these insights, he turns to a critical assessment of jurisprudence both of panels and the Appellate Body. Extensively referring and discussing the literature, he deconstructs findings and decisions in light of implied and assumed underlying philosophies and perceptions as to the relationship of law and science, in particular in the field of food standards. Finding that both positivism and relativism does not provide adequate answers, the author turns critical rationalism and applies the methodologies of falsification developed by Karl R. Popper. Critical rationalism allows combining discourse in science and law and helps preparing the ground for a new approach to risk assessment and risk management. Linking the problem to the doctrine of multilevel governance the author develops a theory allocating risk assessment to international for a while leaving the matter of risk management to national and democratically accountable government. While the author throughout the thesis questions the possibility of separating risk assessment and risk management, the thesis offers new avenues which may assist in structuring a complex and difficult problem

Identifying observable criteria defining a critical situation involving football fans: an expert focus group study

Critical situations (CSs) involving football fans is a well-researched phenomenon with most studies examining factors leading to an escalation of violence (e.g. Braun & Vliegenthart, 2008). However, research so far has fallen short of analysing CSs that do not escalate (e.g. Hylander & Guvå, 2010) as well as establishing observable criteria that constitute such CSs. Granström et al. (2009), for instance, put forward a definition of a CS describing such situations as characterised by a discrepancy between peace and war-making behaviours between police and demonstrators. Still, this definition remains vague and does not provide concrete, defining criteria that can be identified on site. The present study looks beyond fans’ violent acts per se and focuses on these situations with a potentially – but not necessarily - violent outcome. The aim of this preliminary study is to identify observable criteria defining such a CS involving football fans. This focus group comprised of five experts working with football fans in the German-speaking area of Switzerland who discussed observable characteristics of a CS. Inductive content analysis led to the identification of specific criteria such as, “arrest of a fan”, “insufficient distance (<30m) between fans and police” and “fans mask themselves”. These criteria were then assigned to four phases of a CS highlighting the dynamic aspect of this phenomenon: Antecedents, Causes, Reactions, Consequence. Specifically, Causes, Reactions and Consequences are observable on site, while Antecedents include relevant, background information directly influencing a CS. This study puts forward a working definition of a CS that can facilitate the assessment of actual situations in the football context as well as for further research on fan violence prevention and control. These results also highlight similarities with studies investigating fan violence in other European countries while acknowledging unique characteristics of the Swiss German fan culture.

Factors Controlling Species Richness in Alpine Plant Communities: An Assessment of the Importance of Stress and Disturbance

This study explores whether the high variability of vascular plant diversity among alpine plant communities can be explained by stress and/or disturbance intensities. Species numbers of 14 alpine plant communities were sampled in the Swiss Alps. To quantify the intensity of 13 stress and 6 disturbance factors potentially controlling plant life in these communities, a survey was conducted by asking numerous specialists in alpine vegetation to assess the importance of the different factors for each community. The estimated values were combined in stress- and disturbance-indices which were compared with diversity according to the Intermediate Stress Hypothesis, the Intermediate Disturbance Hypothesis, and the Dynamic Equilibrium Model, respectively. Each of these theories explained a part of the variability in the species richness, but only the Dynamic Equilibrium Model provided a complete and consistent explanation. The last model suggests that community species richness within the alpine life zone is generally controlled by stress intensity. Disturbance and competition seem to play a secondary role by fine-tuning diversity in specific communities. As diversity is primarily limited by stress, a moderation of temperature-related stress factors, as a result of global warming, may cause a shift of the equilibrium between stress, disturbance, and competition in alpine ecosystems.

Implications of proposed fibromyalgia criteria across other functional pain syndromes

OBJECTIVES In 2010, the American College of Rheumatology (ACR) proposed new criteria for the diagnosis of fibromyalgia (FM) in the context of objections to components of the criteria of 1990. The new criteria consider the Widespread Pain Index (WPI) and the Symptom Severity Score (SSS). This study evaluated the implications of the new diagnostic criteria for FM across other functional pain syndromes. METHOD A cohort of 300 consecutive in-patients with functional pain syndromes underwent a diagnostic screen according to the ACR 2010 criteria. Additionally, systematic pain assessment including algometric and psychometric data was carried out. RESULTS Twenty-five patients (8.3%) had been diagnosed with FM according to the ACR 1990 criteria. Twenty-one of them (84%) also met the new ACR 2010 criteria. In total, 130 patients (43%) fulfilled the new ACR 2010 criteria. A comparison of new vs. old cases showed a high degree of conformity in most of the pain characteristics. The new FM cases, however, revealed a pronounced heterogeneity in the anatomical pain locations, including several types of localized pain syndromes. Furthermore, patients fulfilling the ACR 2010 FM criteria differed from those with other functional pain syndromes; they had increased pain sensitivity scores and increased psychometric values for depression, anxiety, and psychological distress (p<0.01). CONCLUSIONS FM according to the ACR 2010 criteria describes the 'severe half' of the spectrum of functional pain syndromes. By dropping the requirement of 'generalized pain', these criteria result in a blurring of the distinction between FM and more localized functional pain syndromes.

Treatment allocation in hepatocellular carcinoma: Assessment of the BCLC algorithm

BACKGROUND AND AIMS The Barcelona Clinic Liver Cancer (BCLC) staging system is the algorithm most widely used to manage patients with hepatocellular carcinoma (HCC). We aimed to investigate the extent to which the BCLC recommendations effectively guide clinical practice and assess the reasons for any deviation from the recommendations. MATERIAL AND METHODS The first-line treatments assigned to patients included in the prospective Bern HCC cohort were analyzed. RESULTS Among 223 patients included in the cohort, 116 were not treated according to the BCLC algorithm. Eighty percent of the patients in BCLC stage 0 (very early HCC) and 60% of the patients in BCLC stage A (early HCC) received recommended curative treatment. Only 29% of the BCLC stage B patients (intermediate HCC) and 33% of the BCLC stage C patients (advanced HCC) were treated according to the algorithm. Eighty-nine percent of the BCLC stage D patients (terminal HCC) were treated with best supportive care, as recommended. In 98 patients (44%) the performance status was disregarded in the stage assignment. CONCLUSION The management of HCC in clinical practice frequently deviates from the BCLC recommendations. Most of the curative therapy options, which have well-defined selection criteria, were allocated according to the recommendations, while the majority of the palliative therapy options were assigned to patients with tumor stages not aligned with the recommendations. The only parameter which is subjective in the algorithm, the performance status, is also the least respected.

Assessment of the nonoperated root after apical surgery of the other root in mandibular molars: a 5-year follow-up study

INTRODUCTION If a surgical approach is chosen to treat a multirooted tooth affected by persistent periapical pathosis, usually only the affected roots are operated on. The present study assessed the periapical status of the nonoperated root 5 years after apical surgery of the other root in mandibular molars. METHODS Patients treated with apical surgery of mandibular molars with a follow-up of 5 years were selected. Patient-related and clinical parameters (sex, age, smoking, symptoms, and signs of infection) before surgery were recorded. Preoperative intraoral periapical radiographs and radiographs 5 years after surgery were examined. The following data were collected: tooth, operated root, type and quality of the coronal restoration, marginal bone level, length and homogeneity of the root canal filling, presence of a post/screw, periapical index (PAI) of each root, and radiographic healing of the operated root. The presence of apical pathosis of the nonoperated root was analyzed statistically in relation to the recorded variables. RESULTS Thirty-seven patients fulfilled the inclusion criteria. Signs of periapical pathosis in the nonoperated root 5 years after surgery (PAI ≥ 3) could be observed in only 3 cases (8.1%). Therefore, statistical analysis in relation to the variables was not possible. The PAI of the nonoperated root before surgery had a weak correlation with signs of apical pathosis 5 years after surgery. CONCLUSIONS Nonoperated roots rarely developed signs of new apical pathosis 5 years after apical surgery of the other root in mandibular molars. It appears reasonable to resect and fill only roots with a radiographically evident periapical lesion.

Evaluation of an inventory for the assessment of critical incidents involving football fans

Introduction: Fan violence is a frequent occurrence in Swiss football (Bundesamt für Polizei, 2015) leading to high costs for prevention and control (Mensch & Maurer, 2014). Various theories put forward an explanation of fan violence, such as the Elaborated Social Identity Model (Drury & Reicher, 2000)and the Aggravation Mitigation Model (Hylander & Guvå, 2010). Important observations from these theories are the multi-dimensional understanding of fan violence and the Dynamics occurring in the fan group. Nevertheless, none of them deal with critical incidents (CIs) which involve a tense atmosphere combined with a higher risk of fan violence. Schumacher Dimech, Brechbühl and Seiler (2015) tackled this gap in research and explored CIs where 43 defining criteria were identified and compiled in an integrated model of CIs. The defining criteria were categorised in four higher-order themes “antecedents” (e.g. a documented history of fan rivalry), “triggers” (e.g. the arrest of a fan), “reactions” (e.g. fans masking themselves) and “consequences” (e.g. fans avoiding communication with fan social workers). Methods: An inventory based on this model is being developed including these 43 criteria. In an exploratory phase, this inventory was presented as an online questionnaire and was completed by 143 individuals. Three main questions are examined: Firstly, the individual items are tested using descriptive analyses. An item analysis is conducted to test reliability, item difficulty and discriminatory power. Secondly, the model’s four higher-order themes are tested using exploratory factor analysis (EFA). Thirdly, differences between sub -groups are explored, such as gender and age-related differences. Results: Respondents rated the items’ importance as high and the quota of incomplete responses was not systematic. Two items were removed from the inventory because of low mean or a high rate of “don’t know”-responses. EFA produced a six-factor solution grouping items into match-related factors, repressive measures, fans’ delinquent behaviour, intra-group behaviour, communication and control and inter-group factors. The item “fans consume alcohol” could not be ordered into any category but was retained since literature accentuates this factor’s influence on fan violence. Analyses examining possible differences between groups are underway. Discussion: Results exploring the adequacy of this inventory assessing defining criteria of CIs in football are promising and thus further evaluative investigation is recommended. This inventory can be used in two ways: as a standardised instrument of assessment for experts evaluating specific CIs and as an instrument for exploring differences in perception and assessment of a CI e.g. gender and age differences, differences between interest groups and stakeholders.

Towards science-based sediment quality standards-Effects of field-collected sediments in rainbow trout (Oncorhynchus mykiss).

Sediments can act as long-term sinks for environmental pollutants. Within the past decades, dioxin-like compounds (DLCs) such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) have attracted significant attention in the scientific community. To investigate the time- and concentration-dependent uptake of DLCs and PAHs in rainbow trout (Oncorhynchus mykiss) and their associated toxicological effects, we conducted exposure experiments using suspensions of three field-collected sediments from the rivers Rhine and Elbe, which were chosen to represent different contamination levels. Five serial dilutions of contaminated sediments were tested; these originated from the Prossen and Zollelbe sampling sites (both in the river Elbe, Germany) and from Ehrenbreitstein (Rhine, Germany), with lower levels of contamination. Fish were exposed to suspensions of these dilutions under semi-static conditions for 90 days. Analysis of muscle tissue by high resolution gas chromatography and mass spectrometry and of bile liquid by high-performance liquid chromatography showed that particle-bound PCDD/Fs, PCBs and PAHs were readily bioavailable from re-suspended sediments. Uptake of these contaminants and the associated toxicological effects in fish were largely proportional to their sediment concentrations. The changes in the investigated biomarkers closely reflected the different sediment contamination levels: cytochrome P450 1A mRNA expression and 7-ethoxyresorufin-O-deethylase activity in fish livers responded immediately and with high sensitivity, while increased frequencies of micronuclei and other nuclear aberrations, as well as histopathological and gross pathological lesions, were strong indicators of the potential long-term effects of re-suspension events. Our study clearly demonstrates that sediment re-suspension can lead to accumulation of PCDD/Fs and PCBs in fish, resulting in potentially adverse toxicological effects. For a sound risk assessment within the implementation of the European Water Framework Directive and related legislation, we propose a strong emphasis on sediment-bound contaminants in the context of integrated river basin management plans.