Bone mineral density (BMD), micro-architecture estimation (TBS) and vertebral fracture assessment (VFA) extracted from a single DXA device in combination with clinical risk factors improve significantly the identification of women at high risk of fracture

Introduction: Osteoporosis (OP) is a systemic skeletal disease characterized by a low bone mineral density (BMD) and a micro-architectural (MA) deterioration. Clinical risk factors (CRF) are often used as a MA approximation. MA is yet evaluable in daily practice by the Trabecular Bone Score (TBS) measure. TBS is a novel grey-level texture measurement reflecting bone micro-architecture based on the use of experimental variograms of 2D projection images. TBS is very simple to obtain, by reanalyzing a lumbar DXA-scan. TBS has proven to have diagnosis and prognosis value, partially independent of CRF and BMD. The aim of the OsteoLaus cohort is to combine in daily practice the CRF and the information given by DXA (BMD, TBS and vertebral fracture assessment (VFA)) to better identify women at high fracture risk. Method: The OsteoLaus cohort (1400 women 50 to 80 years living in Lausanne, Switzerland) started in 2010. This study is derived from the cohort COLAUS who started in Lausanne in 2003. The main goals of COLAUS is to obtain information on the epidemiology and genetic determinants of cardiovascular risk in 6700 men and women. CRF for OP, bone ultrasound of the heel, lumbar spine and hip BMD, VFA by DXA and MA evaluation by TBS are recorded in OsteoLaus. Preliminary results are reported. Results: We included 631 women: mean age 67.4±6.7 y, BMI 26.1±4.6, mean lumbar spine BMD 0.943±0.168 (T-score -1.4 SD), TBS 1.271±0.103. As expected, correlation between BMD and site matched TBS is low (r2=0.16). Prevalence of VFx grade 2/3, major OP Fx and all OP Fx is 8.4%, 17.0% and 26.0% respectively. Age- and BMI-adjusted ORs (per SD decrease) are 1.8 (1.2- 2.5), 1.6 (1.2-2.1), 1.3 (1.1-1.6) for BMD for the different categories of fractures and 2.0 (1.4-3.0), 1.9 (1.4-2.5), 1.4 (1.1-1.7) for TBS respectively. Only 32 to 37% of women with OP Fx have a BMD < -2.5 SD or a TBS < 1.200. If we combine a BMD < -2.5 SD or a TBS < 1.200, 54 to 60% of women with an osteoporotic Fx are identified. Conclusion: As in the already published studies, these preliminary results confirm the partial independence between BMD and TBS. More importantly, a combination of TBS subsequent to BMD increases significantly the identification of women with prevalent OP Fx which would have been miss-classified by BMD alone. For the first time we are able to have complementary information about fracture (VFA), density (BMD), micro- and macro architecture (TBS & HAS) from a simple, low ionizing radiation and cheap device: DXA. Such complementary information is very useful for the patient in the daily practice and moreover will likely have an impact on cost effectiveness analysis.

Maps as risk mitigation tools. Adaptation of the Swiss hazard assessment and mapping methodology to a Moroccan site: Beni Mellal

Dans le contexte climatique actuel, les régions méditerranéennes connaissent une intensification des phénomènes hydrométéorologiques extrêmes. Au Maroc, le risque lié aux inondations est devenu problématique, les communautés étant vulnérables aux événements extrêmes. En effet, le développement économique et urbain rapide et mal maîtrisé augmente l'exposition aux phénomènes extrêmes. La Direction du Développement et de la Coopération suisse (DDC) s'implique activement dans la réduction des risques naturels au Maroc. La cartographie des dangers et son intégration dans l'aménagement du territoire représentent une méthode efficace afin de réduire la vulnérabilité spatiale. Ainsi, la DDC a mandaté ce projet d'adaptation de la méthode suisse de cartographie des dangers à un cas d'étude marocain (la ville de Beni Mellal, région de Tadla-Azilal, Maroc). La méthode suisse a été adaptée aux contraintes spécifiques du terrain (environnement semi-aride, morphologie de piémont) et au contexte de transfert de connaissances (caractéristiques socio-économiques et pratiques). Une carte des phénomènes d'inondations a été produite. Elle contient les témoins morphologiques et les éléments anthropiques pertinents pour le développement et l'aggravation des inondations. La modélisation de la relation pluie-débit pour des événements de référence, et le routage des hydrogrammes de crue ainsi obtenus ont permis d'estimer quantitativement l'aléa inondation. Des données obtenues sur le terrain (estimations de débit, extension de crues connues) ont permis de vérifier les résultats des modèles. Des cartes d'intensité et de probabilité ont été obtenues. Enfin, une carte indicative du danger d'inondation a été produite sur la base de la matrice suisse du danger qui croise l'intensité et la probabilité d'occurrence d'un événement pour obtenir des degrés de danger assignables au territoire étudié. En vue de l'implémentation des cartes de danger dans les documents de l'aménagement du territoire, nous nous intéressons au fonctionnement actuel de la gestion institutionnelle du risque à Beni Mellal, en étudiant le degré d'intégration de la gestion et la manière dont les connaissances sur les risques influencent le processus de gestion. L'analyse montre que la gestion est marquée par une logique de gestion hiérarchique et la priorité des mesures de protection par rapport aux mesures passives d'aménagement du territoire. Les connaissances sur le risque restent sectorielles, souvent déconnectées. L'innovation dans le domaine de la gestion du risque résulte de collaborations horizontales entre les acteurs ou avec des sources de connaissances externes (par exemple les universités). Des recommandations méthodologiques et institutionnelles issues de cette étude ont été adressées aux gestionnaires en vue de l'implémentation des cartes de danger. Plus que des outils de réduction du risque, les cartes de danger aident à transmettre des connaissances vers le public et contribuent ainsi à établir une culture du risque. - Severe rainfall events are thought to be occurring more frequently in semi-arid areas. In Morocco, flood hazard has become an important topic, notably as rapid economic development and high urbanization rates have increased the exposure of people and assets in hazard-prone areas. The Swiss Agency for Development and Cooperation (SADC) is active in natural hazard mitigation in Morocco. As hazard mapping for urban planning is thought to be a sound tool for vulnerability reduction, the SADC has financed a project aimed at adapting the Swiss approach for hazard assessment and mapping to the case of Morocco. In a knowledge transfer context, the Swiss method was adapted to the semi-arid environment, the specific piedmont morphology and to socio-economic constraints particular to the study site. Following the Swiss guidelines, a hydro-geomorphological map was established, containing all geomorphic elements related to known past floods. Next, rainfall / runoff modeling for reference events and hydraulic routing of the obtained hydrographs were carried out in order to assess hazard quantitatively. Field-collected discharge estimations and flood extent for known floods were used to verify the model results. Flood hazard intensity and probability maps were obtained. Finally, an indicative danger map as defined within the Swiss hazard assessment terminology was calculated using the Swiss hazard matrix that convolves flood intensity with its recurrence probability in order to assign flood danger degrees to the concerned territory. Danger maps become effective, as risk mitigation tools, when implemented in urban planning. We focus on how local authorities are involved in the risk management process and how knowledge about risk impacts the management. An institutional vulnerability "map" was established based on individual interviews held with the main institutional actors in flood management. Results show that flood hazard management is defined by uneven actions and relationships, it is based on top-down decision-making patterns, and focus is maintained on active mitigation measures. The institutional actors embody sectorial, often disconnected risk knowledge pools, whose relationships are dictated by the institutional hierarchy. Results show that innovation in the risk management process emerges when actors collaborate despite the established hierarchy or when they open to outer knowledge pools (e.g. the academia). Several methodological and institutional recommendations were addressed to risk management stakeholders in view of potential map implementation to planning. Hazard assessment and mapping is essential to an integrated risk management approach: more than a mitigation tool, danger maps represent tools that allow communicating on hazards and establishing a risk culture.

Perfusion ct based thrombolysis in acute ischaemic stroke

Background Despite use in clinical practice and trials of thrombolysis, a non-contrast CT is not sensitive for identifying penumbral tissue in acute stroke. This study evaluated how it compares with physiological imaging using CT perfusion.Methods 40 imaging datasets with non-contrast CT (NCCT) and perfusion CT (CTP) were retrospectively identified. 2 sets of observers (n¼6) and a neuroradiologist made a blind evaluation of the images. Inter-observer agreement was calculated for identifying ischaemic change on NCCT, and abnormalities on cerebral blood flow, time to peak and cerebral blood volume maps. A prospective cohort of 73 patients with anterior circulation cortical strokes were thrombolysed based on qualitative assessment of penumbral tissue on CTP within 3 h of stroke onset. Functional outcome was assessed at 3 months.Results Inter-rater agreement was moderate (k¼0.54) for early ischaemic change on NCCT. Perfusion maps improved this to substantial for deficit in cerebral blood volume (k¼0.67) and almost perfect for time to peak and cerebral blood flow (both k¼0.87). In the prospective arm, 58.9% of patients with cortical strokes were thrombolysed. There was no significant difference in attainment of complete recovery (p¼0.184) between the thrombolysed and nonthrombolysed group.Conclusions We demonstrate how perfusion CT aids clinical decision- making in acute stroke. Good functional outcomes from thrombolysis can be safely achieved using this physiologically informed approach.

Is (1→3)-β-D-glucan the missing link from bedside assessment to pre-emptive therapy of invasive candidiasis?

ABSTRACT: Invasive candidiasis is a frequent life-threatening complication in critically ill patients. Early diagnosis followed by prompt treatment aimed at improving outcome by minimizing unnecessary antifungal use remains a major challenge in the ICU setting. Timely patient selection thus plays a key role for clinically efficient and cost-effective management. Approaches combining clinical risk factors and Candida colonization data have improved our ability to identify such patients early. While the negative predictive value of scores and predicting rules is up to 95 to 99%, the positive predictive value is much lower, ranging between 10 and 60%. Accordingly, if a positive score or rule is used to guide the start of antifungal therapy, many patients may be treated unnecessarily. Candida biomarkers display higher positive predictive values; however, they lack sensitivity and are thus not able to identify all cases of invasive candidiasis. The (1→3)-β-D-glucan (BG) assay, a panfungal antigen test, is recommended as a complementary tool for the diagnosis of invasive mycoses in high-risk hemato-oncological patients. Its role in the more heterogeneous ICU population remains to be defined. More efficient clinical selection strategies combined with performant laboratory tools are needed in order to treat the right patients at the right time by keeping costs of screening and therapy as low as possible. The new approach proposed by Posteraro and colleagues in the previous issue of Critical Care meets these requirements. A single positive BG value in medical patients admitted to the ICU with sepsis and expected to stay for more than 5 days preceded the documentation of candidemia by 1 to 3 days with an unprecedented diagnostic accuracy. Applying this one-point fungal screening on a selected subset of ICU patients with an estimated 15 to 20% risk of developing candidemia is an appealing and potentially cost-effective approach. If confirmed by multicenter investigations, and extended to surgical patients at high risk of invasive candidiasis after abdominal surgery, this Bayesian-based risk stratification approach aimed at maximizing clinical efficiency by minimizing health care resource utilization may substantially simplify the management of critically ill patients at risk of invasive candidiasis.

An empirical hierarchical Bayesian unification of occupational exposure assessment methods.

In occupational exposure assessment of airborne contaminants, exposure levels can either be estimated through repeated measurements of the pollutant concentration in air, expert judgment or through exposure models that use information on the conditions of exposure as input. In this report, we propose an empirical hierarchical Bayesian model to unify these approaches. Prior to any measurement, the hygienist conducts an assessment to generate prior distributions of exposure determinants. Monte-Carlo samples from these distributions feed two level-2 models: a physical, two-compartment model, and a non-parametric, neural network model trained with existing exposure data. The outputs of these two models are weighted according to the expert's assessment of their relevance to yield predictive distributions of the long-term geometric mean and geometric standard deviation of the worker's exposure profile (level-1 model). Bayesian inferences are then drawn iteratively from subsequent measurements of worker exposure. Any traditional decision strategy based on a comparison with occupational exposure limits (e.g. mean exposure, exceedance strategies) can then be applied. Data on 82 workers exposed to 18 contaminants in 14 companies were used to validate the model with cross-validation techniques. A user-friendly program running the model is available upon request.

Engineering, conjugation, and immunogenicity assessment of Escherichia coli O121 O antigen for its potential use as a typhoid vaccine component.

State-of-the-art production technologies for conjugate vaccines are complex, multi-step processes. An alternative approach to produce glycoconjugates is based on the bacterial N-linked protein glycosylation system first described in Campylobacter jejuni. The C. jejuni N-glycosylation system has been successfully transferred into Escherichia coli, enabling in vivo production of customized recombinant glycoproteins. However, some antigenic bacterial cell surface polysaccharides, like the Vi antigen of Salmonella enterica serovar Typhi, have not been reported to be accessible to the bacterial oligosaccharyltransferase PglB, hence hamper development of novel conjugate vaccines against typhoid fever. In this report, Vi-like polysaccharide structures that can be transferred by PglB were evaluated as typhoid vaccine components. A polysaccharide fulfilling these requirements was found in Escherichia coli serovar O121. Inactivation of the E. coli O121 O antigen cluster encoded gene wbqG resulted in expression of O polysaccharides reactive with antibodies raised against the Vi antigen. The structure of the recombinantly expressed mutant O polysaccharide was elucidated using a novel HPLC and mass spectrometry based method for purified undecaprenyl pyrophosphate (Und-PP) linked glycans, and the presence of epitopes also found in the Vi antigen was confirmed. The mutant O antigen structure was transferred to acceptor proteins using the bacterial N-glycosylation system, and immunogenicity of the resulting conjugates was evaluated in mice. The conjugate-induced antibodies reacted in an enzyme-linked immunosorbent assay with E. coli O121 LPS. One animal developed a significant rise in serum immunoglobulin anti-Vi titer upon immunization.

Trabecular Bone Score: A Noninvasive Analytical Method Based Upon the DXA Image.

The trabecular bone score (TBS) is a gray-level textural metric that can be extracted from the two-dimensional lumbar spine dual-energy X-ray absorptiometry (DXA) image. TBS is related to bone microarchitecture and provides skeletal information that is not captured from the standard bone mineral density (BMD) measurement. Based on experimental variograms of the projected DXA image, TBS has the potential to discern differences between DXA scans that show similar BMD measurements. An elevated TBS value correlates with better skeletal microstructure; a low TBS value correlates with weaker skeletal microstructure. Lumbar spine TBS has been evaluated in cross-sectional and longitudinal studies. The following conclusions are based upon publications reviewed in this article: 1) TBS gives lower values in postmenopausal women and in men with previous fragility fractures than their nonfractured counterparts; 2) TBS is complementary to data available by lumbar spine DXA measurements; 3) TBS results are lower in women who have sustained a fragility fracture but in whom DXA does not indicate osteoporosis or even osteopenia; 4) TBS predicts fracture risk as well as lumbar spine BMD measurements in postmenopausal women; 5) efficacious therapies for osteoporosis differ in the extent to which they influence the TBS; 6) TBS is associated with fracture risk in individuals with conditions related to reduced bone mass or bone quality. Based on these data, lumbar spine TBS holds promise as an emerging technology that could well become a valuable clinical tool in the diagnosis of osteoporosis and in fracture risk assessment. © 2014 American Society for Bone and Mineral Research.

Molecular risk assessment of BIG 1-98 participants by expression profiling using RNA from archival tissue.

Background: The purpose of the work reported here is to test reliable molecular profiles using routinely processed formalin-fixed paraffin-embedded (FFPE) tissues from participants of the clinical trial BIG 1-98 with a median follow-up of 60 months. Methods: RNA from fresh frozen (FF) and FFPE tumor samples of 82 patients were used for quality control, and independent FFPE tissues of 342 postmenopausal participants of BIG 1-98 with ER-positive cancer were analyzed by measuring prospectively selected genes and computing scores representing the functions of the estrogen receptor (eight genes, ER_8), the progesterone receptor (five genes, PGR_5), Her2 (two genes, HER2_2), and proliferation (ten genes, PRO_10) by quantitative reverse transcription PCR (qRT-PCR) on TaqMan Low Density Arrays. Molecular scores were computed for each category and ER_8, PGR_5, HER2_2, and PRO_10 scores were combined into a RISK_25 score. Results: Pearson correlation coefficients between FF- and FFPE-derived scores were at least 0.94 and high concordance was observed between molecular scores and immunohistochemical data. The HER2_2, PGR_ 5, PRO_10 and RISK_25 scores were significant predictors of disease free-survival (DFS) in univariate Cox proportional hazard regression. PRO_10 and RISK_25 scores predicted DFS in patients with histological grade II breast cancer and in lymph node positive disease. The PRO_10 and PGR_ 5 scores were independent predictors of DFS in multivariate Cox regression models incorporating clinical risk indicators; PRO_10 outperformed Ki-67 labeling index in multivariate Cox proportional hazard analyses. Conclusions: Scores representing the endocrine responsiveness and proliferation status of breast cancers were developed from gene expression analyses based on RNA derived from FFPE tissues. The validation of the molecular scores with tumor samples of participants of the BIG 1-98 trial demonstrates that such scores can serve as independent prognostic factors to estimate disease free survival (DFS) in postmenopausal patients with estrogen receptor positive breast cancer.

The attractiveness of nations in global competition : an empirical assessment of the effects of country attractiveness on the success of strategy for hosting international sports events, 1990-2012

This dissertation aims to investigate empirical evidence on the importance and influence of attractiveness of nations in global competition. The notion of country attractiveness, which has been widely developed in the research areas of international business, tourism and migration, is a multi-dimensional construct to measure a country's characteristics with regard to its market or destination that attract international investors, tourists and migrants. This analytical concept provides an account of the mechanism as to how potential stakeholders evaluate more attractive countries based on certain criteria. Thus, in the field of international sport-event bidding, do international sport event owners also have specific country attractiveness for their sport event hosts? The dissertation attempts to address this research question by statistically assessing the effects of country attractiveness on the success of strategy for hosting international sports events. Based on theories of signaling and soft power, country attractiveness is defined and measured as the three dimensions of sustainable development: economic, social, and environmental attractiveness. This thesis proceeds to examine the concept of sport-event-hosting strategy and explore multi-level factors affecting the success in international sport-event bidding. By exploring past history of the Olympic Movement from theoretical perspectives, the thesis proposes and tests the hypotheses that economic, social and environmental attractiveness of a country may be correlated with its bid wins or the success of sport-event-hosting strategy. Quantitative analytical methods with various robustness checks are employed with using collected data on bidding results of major events in Olympic sports during the period from 1990 to 2012. The analysis results reveal that event owners of international Olympic sports are likely to prefer countries that have higher economic, social, and environmental attractiveness. The empirical assessment of this thesis suggests that high country attractiveness can be an essential element of prerequisites for a city/country to secure in order to bid with an increased chance of success.

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: a comparative risk assessment.

BACKGROUND: High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. METHODS: We used data for exposure to risk factors by country, age group, and sex from pooled analyses of population-based health surveys. We obtained relative risks for the effects of risk factors on cause-specific mortality from meta-analyses of large prospective studies. We calculated the population attributable fractions for each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific population attributable fractions by the number of disease-specific deaths. We obtained cause-specific mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the final estimates. FINDINGS: In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10·8 million deaths, 95% CI 10·1-11·5) of deaths from these diseases in 2010 were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7·1 million deaths, 6·6-7·6) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined effects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. INTERPRETATION: The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing effect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the global response to non-communicable diseases. FUNDING: UK Medical Research Council, US National Institutes of Health.

Proposal of a new classification for optimising outcome assessment following partial cricotracheal resections in severe pediatric subglottic stenosis.

OBJECTIVE: Creation of a patent subglottic airway after partial cricotracheal resection (PCTR) may not always result in successful decannulation due to associated parameters such as co-morbidity and/or glottic involvement. We classified patients after incorporating these additional parameters into the original Myer-Cotton classification to assess whether this could better predict the outcome measures after PCTR. METHODS: One hundred children with Myer-Cotton grade III or IV subglottic stenosis who underwent PCTR between 1978 and 2008 were identified from a prospectively collected database. The patients were classified into four groups based on the association of co-morbidity and/or glottic involvement. Delay in decannulation, revision open surgery and rates of decannulation were the outcome measures compared between the groups. RESULTS: There were 68 children with Myer-Cotton grade III and 32 children with grade IV stenosis. Based on the new classification, there were 36 children with isolated SGS, 31 with associated co-morbidity, 19 with associated glottic involvement and 14 children with both co-morbidity and glottic involvement. A trend towards less optimal results was noticed with the association of co-morbidity and/or glottic involvement. Statistical significance was reached for maximum decannulation failure in the group with both co-morbidity and glottic involvement. Delayed decannulation significantly correlated in the group with associated glottic involvement. CONCLUSION: This new classification is relatively simple and aimed at providing more accurate and uniform prognostic information to both patients and surgeons when dealing with the whole spectrum of severe SGS.

Konsensusempfehlungen zur Beurteilung der medizinischen Mindestanforderungen für Fahreignung bei kognitiver Beeinträchtigung [Consensus recommendations for the assessment of fitness to drive in cognitively impaired patients].

Memory Clinics provide evidence based diagnosis and treatment of dementia. Whenever a diagnosis of dementia is made, it is important to inform the patients about the possible impact of dementia on driving. Patients and their next of kin require competent advice whenever this difficult question is addressed and the mobility desire and the risks related to driving need to be carefully weight up. The time of diagnosis does not necessarily equate to the time when a person with dementia becomes an unsafe driver. The cause and severity of dementia, comorbidities and the current medication need to be carefully taken into account for this decision. On behalf of the association of the Swiss Memory Clinics, a group of experts has developed recommendations to assess fitness to drive in cognitively impaired older adults.

Assessment of free-living physical activity in humans: an overview of currently available and proposed new measures.

The number of physical activity measures and indexes used in the human literature is large and may result in some difficulty for the average investigator to choose the most appropriate measure. Accordingly, this review is intended to provide information on the utility and limitations of the various measures. Its primary focus is the objective assessment of free-living physical activity in humans based on physiological and biomechanical methods. The physical activity measures have been classified into three categories: Measures based on energy expenditure or oxygen uptake, such as activity energy expenditure, activity-related time equivalent, physical activity level, physical activity ratio, metabolic equivalent, and a new index of potential interest, daytime physical activity level. Measures based on heart rate monitoring, such as net heart rate, physical activity ratio heart rate, physical activity level heart rate, activity-related time equivalent, and daytime physical activity level heart rate. Measures based on whole-body accelerometry (counts/U time). Quantification of the velocity and duration of displacement in outdoor conditions by satellites using the Differential Global Positioning System may constitute a surrogate for physical activity, because walking is the primary activity of man in free-living conditions. A general outline of the measures and indexes described above is presented in tabular form, along with their respective definition, usual applications, advantages, and shortcomings. A practical example is given with typical values in obese and non-obese subjects. The various factors to be considered in the selection of physical activity methods include experimental goals, sample size, budget, cultural and social/environmental factors, physical burden for the subject, and statistical factors, such as accuracy and precision. It is concluded that no single current technique is able to quantify all aspects of physical activity under free-living conditions, requiring the use of complementary methods. In the future, physical activity sensors, which are of low-cost, small-sized, and convenient for subjects, investigators, and clinicians, are needed to reliably monitor, during extended periods in free-living situations, small changes in movements and grade as well as duration and intensity of typical physical activities.

Detailed assessment of the deep-seated gravitational deformation at Stampa above Flåm, Norway

The unstable rock slope above the village of Flåm shows signs of active and postglacial gravitational deformation over an area of 11 km2. We performed detailed structural field mapping, annual differential Global Navigation Satellite System (GNSS) surveys, and generated a detailed topographic model based on airborne and terrestrial laser scanning. Kinematic analyses of the structural data indicates that deformation is complex and varies over the slope. Both sliding and toppling are locally feasible. Using differential GNSS, 18 points were measured annually over a period of up to 6 years. Two of these points show an average yearly movement of around 10 mm/year. They are located at the frontal cliff on almost completely detached blocks. Large fractures indicate deep-seated gravitational deformation of volumes up to 80 million m3, but the movement rates in these areas are below 2 mm/year. Based upon these combined observations, we interpret that small collapses of blocks along the frontal cliff will be more frequent. Larger collapses of free-standing blocks along the cliff with volumes >100,000 m3, thus large enough to reach the fjord, cannot be ruled out. A large collapse involving more than 10 million m3, however, is of very low likelihood at present.

Assessment of left coronary artery beat-to-beat repositioning in order to propose an optimal acquisition window for coronary MRA

Introduction: Coronary magnetic resonance angiography (MRA) is a medical imaging technique that involves collecting data from consecutive heartbeats, always at the same time in the cardiac cycle, in order to minimize heart motion artifacts. This technique relies on the assumption that coronary arteries always follow the same trajectory from heartbeat to heartbeat. Until now, choosing the acquisition window in the cardiac cycle was based exclusively on the position of minimal coronary motion. The goal of this study was to test the hypothesis that there are time intervals during the cardiac cycle when coronary beat-to-beat repositioning is optimal. The repositioning uncertainty values in these time intervals were then compared with the intervals of low coronary motion in order to propose an optimal acquisition window for coronary MRA. Methods: Cine breath-hold x-ray angiograms with synchronous ECG were collected from 11 patients who underwent elective routine diagnostic coronarography. Twenty-three bifurcations of the left coronary artery were selected as markers to evaluate repositioning uncertainty and velocity during cardiac cycle. Each bifurcation was tracked by two observers, with the help of a user-assisted algorithm implemented in Matlab (The Mathworks, Natick, MA, USA) that compared the trajectories of the markers coming from consecutive heartbeats and computed the coronary repositioning uncertainty with steps of 50ms until 650ms after the R-wave. Repositioning uncertainty was defined as the diameter of the smallest circle encompassing the points to be compared at the same time after the R-wave. Student's t-tests with a false discovery rate (FDR, q=0.1) correction for multiple comparison were applied to see whether coronary repositioning and velocity vary statistically during cardiac cycle. Bland-Altman plots and linear regression were used to assess intra- and inter-observer agreement. Results: The analysis of left coronary artery beat-to-beat repositioning uncertainty shows a tendency to have better repositioning in mid systole (less than 0.84±0.58mm) and mid diastole (less than 0.89±0.6mm) than in the rest of the cardiac cycle (highest value at 50ms=1.35±0.64mm). According to Student's t-tests with FDR correction for multiple comparison (q=0.1), two intervals, in mid systole (150-200ms) and mid diastole (550-600ms), provide statistically better repositioning in comparison with the early systole and the early diastole. Coronary velocity analysis reveals that left coronary artery moves more slowly in end systole (14.35±11.35mm/s at 225ms) and mid diastole (11.78±11.62mm/s at 625ms) than in the rest of the cardiac cycle (highest value at 25ms: 55.96±22.34mm/s). This was confirmed by Student's t-tests with FDR correction for multiple comparison (q=0.1, FDR-corrected p-value=0.054): coronary velocity values at 225, 575 and 625ms are not much different between them but they are statistically inferior to all others. Bland-Altman plots and linear regression show that intra-observer agreement (y=0.97x+0.02 with R²=0.93 at 150ms) is better than inter-observer (y=0.8x+0.11 with R²=0.67 at 150ms). Discussion: The present study has demonstrated that there are two time intervals in the cardiac cycle, one in mid systole and one in mid diastole, where left coronary artery repositioning uncertainty reaches points of local minima. It has also been calculated that the velocity is the lowest in end systole and mid diastole. Since systole is less influenced by heart rate variability than diastole, it was finally proposed to test an acquisition window between 150 and 200ms after the R-wave.