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We introduce scrAPP, a smartphone app that helps designers reuse odd-shaped scrap sheet materials. scrAPP uses a smartphone camera to capture the contour of scrap materials providing precise measurements on the spot enabling users to quickly determine if their CAD models will fit on the material and to then place the models for cutting. This work contributes to the body of work focused on sustainability in digital fabrication through the development of tools for designers. The paper describes the rationale and user-centered approach to the development of scrAPP as well as insights into the needs of creative users gathered from an exploratory preliminary user study. A number of challenges in terms of technical implementation and user experience are explored, and conclusions on the future support for mobile material reuse are provided.

This paper presents a knee brace design that applies an extension moment to unload the muscles in stance phase during gait, and thereby the knee, as alternative to conventional valgus braces for knee osteoarthritis patients. The concept was tested on one healthy subject during normal gait with a prototype, which was designed to activate and deactivate in order to apply the extension moment in the stance phase only and hereby avoid any interference during the swing phase. Electromyography measurements and musculoskeletal models were used to evaluate the brace effects on muscle activation and knee compressive forces, respectively. Simulations predicted an ideal reduction of up to 36%, whereas experimental tests revealed a reduction of up to 24% with the current prototype. The prototype brace also reduced the knee joint force impulse up to 9% and electromyography (EMG) peak signal of the vasti muscles with up to 19%. Due to these reductions on a healthy subject, this bracing approach seems promising for reducing knee loads during normal gait. However, further clinical experiments on knee osteoarthritis patients are required to evaluate the effect on both pain and disease progression.

IntroductionAtrial fibrillation is the most common heart arrhythmia with a prevalence of approximately 2% in the western world. Atrial fibrillation is associated with an increased risk of death and morbidity. In many patients, a rate control strategy is recommended. The optimal heart rate target is disputed despite the results of the the RAte Control Efficacy in permanent atrial fibrillation: a comparison between lenient vs strict rate control II (RACE II) trial.Our primary objective will be to investigate the effect of lenient rate control strategy (Methods and analysisWe plan a two-group, superiority randomised clinical trial. 350 outpatients with persistent or permanent atrial fibrillation will be recruited from four hospitals, across three regions in Denmark. Participants will be randomised 1:1 to a lenient medical rate control strategy (Ethics and disseminationEthics approval was obtained through the ethics committee in Region Zealand. The design and findings will be published in peer-reviewed journals as well as be made available on ClinicalTrials.gov.Trial registration numberNCT04542785.

Visual Abstract, Highlights • The GLP-1RAs liraglutide and semaglutide reduce cardiovascular risk in type 2 diabetes patients. • In ApoE−/− mice and LDLr−/− mice, liraglutide and semaglutide treatment significantly attenuated plaque lesion development, in part independently of body weight and cholesterol lowering. • Semaglutide decreased levels of plasma markers of systemic inflammation in an acute inflammation model (lipopolysaccharide), and transcriptomic analysis of aortic atherosclerotic tissue revealed that multiple inflammatory pathways were down-regulated by semaglutide., Summary The glucagon-like peptide-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide reduce cardiovascular risk in type 2 diabetes patients. The mode of action is suggested to occur through modified atherosclerotic progression. In this study, both of the compounds significantly attenuated plaque lesion development in apolipoprotein E-deficient (ApoE−/−) mice and low-density lipoprotein receptor-deficient (LDLr−/−) mice. This attenuation was partly independent of weight and cholesterol lowering. In aortic tissue, exposure to a Western diet alters expression of genes in pathways relevant to the pathogenesis of atherosclerosis, including leukocyte recruitment, leukocyte rolling, adhesion/extravasation, cholesterol metabolism, lipid-mediated signaling, extracellular matrix protein turnover, and plaque hemorrhage. Treatment with semaglutide significantly reversed these changes. These data suggest GLP-1RAs affect atherosclerosis through an anti-inflammatory mechanism.

This paper presents a mapping review of status and trends in research of citizen science, crowdsourcing or community-driven research from 2013–2018. The focus was on identifying themes, trends and gaps in this knowledge collaboration field in general and in relation to learning and education in specific. 240 studies were identified through iterative searches and screening processes, and 15 themes were identified through grounded-theory inspired analysis: 1. Motivation; 2. Evaluation; 3. Education and learning; 4. Man-machine collaboration; 5. Participant experience; 6. Impact on research; 7. CS technologies; 8. Big data; 9. System or project design; 10. Social media; 11. Participant development of research; 12. Behaviour; 13. Ethics; 14; Cross-disciplinary partnerships; 15. Organisational change. Because our focus was on learning, we defined themes with a focus on traditional educational activity and new forms of learning in the field. The review revealed central discussions on the potentials of technology in CS learning. In this paper, we present the project, Community Drive, as well as the theoretical and empirical background on which the project is based. Through technical and humanistic collaboration, the project aims to create models that allow children and young people to participate in overcoming future challenges in cities by becoming active and contributing participants in research and development efforts. Further, the project contributes knowledge about community-driven game tools, user-driven big data and the Internet of Things and their connection with intelligent and socially responsible urban development. The project is conducted in cooperation with the city of Copenhagen, local schools and Aalborg University. Community Drive involves students, aged 10–13, attending schools in deprived neighbourhoods near Aalborg University Copenhagen in southern Copenhagen. This area is characterised by a high rate of unemployment, low income and residents with little or no education. As a result, resources have been allocated for reconditioning the subsidised housing in this area. In this paper, we discuss the ways in which Community Drive, initiated in May 2018, is based on the results of pilot projects conducted from 2014 to 2017. Overall, these studies showed that tasking students with changing their living conditions by redesigning their neighbourhoods is a strong motivational factor. During the redesign process, students were able to construct game-based models of various residents’ needs and argue for redesigns based on their knowledge about the area and the ability of certain designs to fulfil the needs of various groups of residents living in the area. We also present initial results from collaboration workshops between schools and professional external local partners. These results show that three themes are central for the collaboration process: building local contact, meaningful local ownership and real challenges and applicable solutions.

Background Studies of children with food allergy typically only include the mother, and have not investigated the relationship between the amount of allergen needed to elicit a clinical reaction (threshold) and health-related quality of life (HRQL). Our aims were 1) to compare self-reported and parent-reported HRQL in different age groups, 2) to evaluate the impact of severity of allergic reaction and threshold on HRQL, and 3) to investigate factors associated with patient-reported and parent-reported HRQL. Methods Age-appropriate Food Allergy Quality of Life Questionnaires (FAQLQ) were completed by 73 children, 49 adolescents, and 29 adults with peanut, hazelnut or egg allergy. Parents (197 mothers, 120 fathers) assessed their child's HRQL using the FAQLQ-Parent form. Clinical data and threshold values were obtained from a hospital database. Significant factors for HRQL were investigated using univariate and multivariate regression. Results Female patients reported greater impact of food allergy on HRQL than males did. Egg and hazelnut thresholds did not affect HRQL, but lower peanut threshold was associated with worse HRQL. Both parents scored their child's HRQL better than the child's own assessment, but whereas mother-reported HRQL was significantly affected by limitations in the child's social life, father-reported HRQL was affected by limitations in the family's social life. Severity of allergic reaction did not contribute significantly to HRQL. Conclusion The risk of accidental allergen ingestion and limitations in social life are associated with worse HRQL. Fathers provide a unique perspective and should have a greater opportunity to contribute to food allergy research. This article is protected by copyright. All rights reserved.

Introduction and hypothesis To establish the contribution of maternal, fetal and intrapartum factors to the risk of incidence of obstetric anal sphincter injuries (OASIS) and assess the feasibility of an OASIS risk prediction model based on variables available to clinicians prior to birth. Methods This was a population-based, retrospective cohort study using single-site data from the birth database of Aarhus University Hospital, Denmark. The participants were all women who had a singleton vaginal birth during the period 1989 to 2006. Univariate and multivariate logistic regression analyses were performed using multiple imputations for missing data and internally validated using bootstrap methods. The main outcome measures were the contributions of maternal, fetal and intrapartum events to the incidence of OASIS. Results A total of 71,469 women met the inclusion criteria, of whom 1,754 (2.45 %) sustained OASIS. In the multivariate analysis of variables known prior to birth, maternal age 20 – 30 years (OR 1.65, 95 % CI 1.44 – 1.89) and ≥30 years (OR 1.60, 95 % CI 1.39 – 1.85), occipitoposterior fetal position (OR 1.34, 95 % CI 1.06 – 1.70), induction/augmentation of labour (OR 1.46, 95 % CI 1.32 – 1.62), and suspected macrosomia (OR 2.20, 95 % CI 1.97 – 2.45) were independent significant predictors of OASIS, with increasing parity conferring a significant protective effect. The ‘prebirth variable’ model showed a 95 % sensitivity and a 24 % specificity in predicting OASIS with 1 % probability, and a 3 % sensitivity and a 99 % specificity in predicting OASIS with a 10 % probability. Conclusions Our model identified several significant OASIS risk factors that are known prior to actual birth. The prognostic model shows potential for ruling out OASIS (high sensitivity with a low risk cut-off value), but is not useful for ruling in the event. Electronic supplementary material The online version of this article (doi:10.1007/s00192-016-3125-2) contains supplementary material, which is available to authorized users.

According to the wind turbine standard IEC 61400-1, structural integrity of wind turbines is determined either by direct reference to wind data or by load calculation. In both cases, deterministic values are applied and uncertainties neglected for the wind climate parameters and the structural resistance. The uncertainty related to the wind climate parameters depends highly on the presence, duration and quality of on-site wind measurements, and the perturbations introduced by flow modelling. For the wind speed distribution, the uncertainty is considered in assessment of the annual energy production. For other wind climate parameters which potentially have a large influence on the wind turbine loads, the uncertainty is often not well investigated. This paper presents a probabilistic framework for assessment of the structural reliability level of wind turbines in fatigue loading. Uncertainty of the site specific wind climate parameters at each turbine position is estimated based on the local wind measurements, speed-up factors and the distance between the wind turbine and the measuring position. The framework is demonstrated for a wind turbine project in flat terrain. The results show that the uncertainty in the site specific wind climate parameters normally accounts for 10–30% of the total uncertainty in the structural reliability analyses.

WOS: 000468732700018, PubMed ID: 31054483, Background and aims: One of the objectives of the ESC-EORP EUROASPIRE V survey is to determine how well European guidelines on the management of dyslipidaemias are implemented in coronary patients. Methods: Standardized methods were used by trained technicians to collect information on 7824 patients from 130 centers in 27 countries, from the medical records and at a visit at least 6 months after hospitalization for a coronary event. All lipid measurements were performed in one central laboratory. Patients were divided into three groups: on high-intensity LDL-C-lowering-drug therapy (LLT), on low or moderate-intensity LLT and on no LLT. Results: At the time of the visit, almost half of the patients were on a high-intensity LLT. Between hospital discharge and the visit, LLT had been reduced in intensity or interrupted in 20.8% of the patients and had been started or increased in intensity in 11.7%. In those who had interrupted LLT or had reduced the intensity, intolerance to LLT and the advice of their physician were reported as the reason why in 15.8 and 36.8% of the cases, respectively. LDL-C control was better in those on a high-intensity LLT compared to those on low or moderate intensity LLT. LDL-C control was better in men than women and in patients with self-reported diabetes. Conclusions: The results of the EUROASPIRE V survey show that most coronary patients have a less than optimal management of LDL-C. More professional strategies are needed, aiming at lifestyle changes and LLT adapted to the need of the individual patient., ESC - EORP; AmgenAmgen; Eli LillyEli Lilly; PfizerPfizer; SanofiSanofi-Aventis; Ferrer; Novo NordiskNovo Nordisk, The EUROASPIRE V survey was carried out under the auspices of the ESC - EORP. Since the start of EORP, the following companies have supported the programme: Amgen, Eli Lilly, Pfizer, Sanofi, Ferrer and Novo Nordisk. The sponsors of the EUROASPIRE surveys had no role in the design, data collection, data analysis, data interpretation, decision to publish, or writing the manuscript.

The aim of this study was to investigate whether the implementation of the Safewards model reduces the frequency of coercive measures in adult psychiatric inpatient units. Data on all coercive measures performed in psychiatric hospitals in the Region of Southern Denmark 1/1/2012-31/3/2017 were collected retrospectively through The Register of Coercive Measures in Psychiatric Treatment. Interrupted time series analysis by segmented regressions with poisson models were performed on overall coercive measures (n = 12,660), mechanical restraint (n = 2948) and forced sedation (n = 4373). A 2% (95% CI: 1%-4%, p 0.001) decrease per quarter in the frequency of coercive measures and an 11% (95% CI: 8%-13%, p 0.001) decrease per quarter in the frequency of forced sedation were found after the implementation of the Safewards model. In conclusion, the implementation of the Safewards model in adult psychiatric inpatient units was associated with a decrease in forced sedation and potentially the overall use of coercive measures.

In site suitability assessment of wind turbines, it is often the case that one or several wind climate parameters exceed the reference values for the wind turbine design class. In such cases, the IEC 61400-1 requires a load calculation based on the site specific wind climate conditions in order to document the structural integrity. This load calculation demands a significant number of aero-elastic simulations which are time consuming to perform and require expert knowledge. In this paper it is investigated, to which extent the site specific loads can be determined based on a response surface methodology (RSM). Two response surfaces are presented, formulated based on Taylor approximation and Central Composite Design. For each RSM, the model uncertainty is estimated for different combinations of the wind climate parameters, along with the statistical uncertainty introduced by a limited number of random seeds. The results show that fatigue loads during power production, in general, can be assessed accurately using both RSMs. However, central composite design introduces the smallest model uncertainty. For ultimate loads resulting from extreme turbulent inflow, a larger model uncertainty is introduced. Central composite design leads, again, to the lowest model uncertainty. The statistical uncertainty related to the number of aero-elastic simulations is modelled for each RSM using bootstrapping. In general, the statistical uncertainty related to the number of random seeds is larger than the model uncertainty related to the RSMs.

Background/Aims: Murine nephrotoxic nephritis (NTN) is a well-established model resembling chronic kidney disease. Investigating gene expression patterns separately in the glomerular and cortical tubulointerstitial structure could provide new knowledge about structure-specific changes in expression of genes in the NTN model. Methods: Glomerular, cortical tubulointerstitial and whole kidney tissues from mice subjected to nephrotoxic serum (NTS) or phosphate buffered saline (PBS) were collected on day 7, 21 and 42 using laser microdissection (LMD). Total RNA was extracted and subjected to nCounter NanoString. Histology, immunohistochemistry, in situ hybridization and/or quantitative real time PCR (qRT PCR) were performed to confirm regulation of selected genes. Results: LMD provided detailed information about genes that were regulated differently between structures over time. Some of the fibrotic and inflammatory genes (Col1a1, Col3a1 and Ccl2) were upregulated in both structures, whereas other genes such as Spp1 and Grem1 were differentially regulated suggesting spatial pathogenic mechanisms in the kidney. Downregulation of cortical tubulointerstitium genes involved in iron metabolism was detected along with iron accumulation. Conclusion: This study demonstrates several regulated genes in pathways important for the pathogenesis of the NTN model and that LMD identifies structure-specific changes in gene expression during disease development. Furthermore, this study shows the benefits of isolating glomeruli and cortical tubulointerstitium in order to identify gene regulation.

Background and Aim. Interleukin-21 (IL-21) is primarily a T cell-derived cytokine; it is upregulated in patients with Crohn’s Disease (CD) and could be a potential new therapeutic target in CD. Methods. In human material, IL-21 and IL-21R expression was investigated by in situ hybridization (ISH) and immunohistochemistry (IHC) in noninflammatory bowel disease (non-IBD) controls and patients with CD. The pathologic role of IL-21 was examined in murine models of T cell-dependent and T cell-independent colitis, either with a neutralizing monoclonal antibody against IL-21 or with the transfer of CD4+CD45RBhighIL-21R−/− T cells. Colonic pathology was examined by endoscopy, histopathology, IHC, ELISA, and Luminex. Results. In the human intestine, IL-21 and IL-21R mRNA and protein-expressing cells were observed in the mucosa, in lymphoid aggregates of submucosa in non-IBD controls, and in lymphoid aggregates of muscularis externa in patients with CD. IL-21 expression was most abundant in germinal centers (GCs) of the lymphoid aggregates, and IL-21R expression assessed semiquantitatively, was significantly higher in patients with CD compared to non-IBD controls. Following prophylactic and interventive anti-IL-21 mAb treatment in the adoptive transfer (AdTr) model, clinical and pathological parameters were significantly reduced. The most persistent finding was a reduction in colonic infiltrating neutrophils. As well, Rag2−/− mice receiving CD4+CD45RBhighIL-21R−/− T cells developed less severe colitis compared to Rag2−/− mice receiving CD4+CD45RBhighIL-21R+/+ T cells. No effect of reduced IL-21 signalling was observed in T cell-independent colitis. Conclusion. Our study shows that patients with CD have significant expression of IL-21 and IL-21R in the gut. As well, we show that neutralization of IL-21 in experimental T cell-driven colitis is associated with a reduction in clinical and pathological findings. This amelioration seems to be associated with a reduction in colon-infiltrating neutrophils.

Temperature, precipitation and humidity are known to be important factors for the development of schistosome parasites as well as their intermediate snail hosts. Climate therefore plays an important role in determining the geographical distribution of schistosomiasis and it is expected that climate change will alter distribution and transmission patterns. Reliable predictions of distribution changes and likely transmission scenarios are key to efficient schistosomiasis intervention-planning. However, it is often difficult to assess the direction and magnitude of the impact on schistosomiasis induced by climate change, as well as the temporal transferability and predictive accuracy of the models, as prevalence data is often only available from one point in time. We evaluated potential climate-induced changes on the geographical distribution of schistosomiasis in Zimbabwe using prevalence data from two points in time, 29 years apart; to our knowledge, this is the first study investigating this over such a long time period. We applied historical weather data and matched prevalence data of two schistosome species (Schistosoma haematobium and S. mansoni). For each time period studied, a Bayesian geostatistical model was fitted to a range of climatic, environmental and other potential risk factors to identify significant predictors that could help us to obtain spatially explicit schistosomiasis risk estimates for Zimbabwe. The observed general downward trend in schistosomiasis prevalence for Zimbabwe from 1981 and the period preceding a survey and control campaign in 2010 parallels a shift towards a drier and warmer climate. However, a statistically significant relationship between climate change and the change in prevalence could not be established.

Objective: To evaluate the use of palpation of the coccyx (the coccygeal movement test, CMT) as a possible objective screening tool for the assessment of adequate localization of the pelvic floor muscles (PFMs). Subjects and Methods: Twenty-four healthy female volunteers, known to be able to locate their PFMs, were given instructions (allocated at random) to perform a ‘correct contraction', ‘straining' or ‘nothing' when examined by six independent assessors using the CMT. The assessors were blinded to the instructions and to the test results recorded by other assessors. Data were available for 137 observations, and these were dichotomized into either ‘able to contract' (‘correct contraction') or ‘not able to contract' (‘straining' or ‘nothing'). This information was used to calculate the sensitivity, specificity and positive and negative predictive values for the CMT. Results: The CMT correctly identified 56/58 observations when women did not perform the contraction of the PFMs compared to 61/79 observations when they did. Hence, the sensitivity and specificity were 97 and 77%, respectively. Conclusion: This study showed that the CMT was a useful test to identify women who were able to localize their PFMs compared to those who were not, making it a potentially useful initial screening test in structured training programmes for the PFMs.

Hay-making structures are part of the agricultural landscape of meadows and pastures. Hay meadows are still used and found all over Europe, but their distribution patterns as well as their characteristics and regional features depend on geographical area, climate, culture, and intensity of agriculture. Intensively used hay meadows are the most dominant, using heavy machinery to store hay mostly as rounded or square bales. Traditional hay-making structures represent structures or constructions, used to quickly dry freshly cut fodder and to protect it from humidity. The &lsquo, ancient&rsquo, forms of traditional hay-making structures are becoming a relic, due to mechanisation and the use of new technologies. Both the need for drying hay and the traditional methods for doing so were similar across Europe. Our study of hay-making structures focuses on their current state, their development and history, current use and cultural values in various European countries. Regarding the construction and use of hay-making structures, we have distinguished three different types, which correlate to natural and regional conditions: (1) temporary hay racks of various shapes, (2) hay barracks, a special type of shelters for storing hay and (3) different types of permanent construction and buildings for drying and storing hay. Hay-making structures have been mostly preserved in connection with traditional agricultural landscapes, and particularly in the more remote regions or where associated with strong cultural identity.

Site-specific assessment of wind turbine design requires verification that the individual wind turbine components can survive the site-specific wind climate. The wind turbine design standard, IEC 61400-1 (third edition), describes how this should be done using a simplified, equivalent wind climate established from the on-site distribution functions of the horizontal mean wind speeds, the 90% quantile of turbulence along with average values of vertical wind shear and air density and the maximum flow inclination. This paper investigates the accuracy of fatigue loads estimated using this equivalent wind climate required by the current design standard by comparing damage equivalent fatigue loads estimated based on wind climate parameters for each 10 min time-series with fatigue loads estimated based on the equivalent wind climate parameters. Wind measurements from Boulder, CO, in the United States and Høvsøre in Denmark have been used to estimate the natural variation in the wind conditions between 10 min time periods. The structural wind turbine loads have been simulated using the aero-elastic model FAST. The results show that using a 90% quantile for the turbulence leads to an accurate assessment of the blade root flapwise bending moment and a conservative assessment of the tower bottom for-aft bending moment and low speed shaft torque. Currently, IEC 61400-1 (third edition) neglects the variation in wind shear by using the average value. This may lead to a nonconservative assessment of blade root flapwise fatigue loads, which are sensitive to wind shear. The results in this paper indicate that using a 75% quantile for the wind shear at each wind speed bin leads to an appropriate, but conservative, assessment of the fatigue loads. However, care should be taken when using this approach for components where low or negative wind shears can lead to large fatigue loads. This is the case for some drivetrain components where a lower quantile may be required.

Minimized extracorporeal circulation systems in coronary artery bypass may have less impairing effect on hematological parameters and bleeding compared to conventional systems. The aim of this study was to investigate whether the use of mini systems does result in an increased postoperative hypercoagulative status.Patients with increased risk of postoperative blood transfusion were randomly allocated to coronary bypass surgery using conventional or minimized extracorporeal circulation. Serial thrombelastographic analysis was performed preoperatively, at day 1 and 5.Forty-six patients were included. In 56% of the patients in the experimental and in 62% in the control group an activated coagulation system, measured as maximal amplitude above normal reference was found preoperatively. This was normalized the day after operation. At day 5 a significant number of patients in the experimental group (p = 0.03) overshooted the preoperative maximal clot strength compared to the control group (p = 0.15); however, a direct intergroup analysis showed no difference. In both groups, hemoglobin levels and platelet counts decreased at day one after surgery. At day 5, hemoglobin was partly and platelets completely normalized. No differences were found with respect to transfusion needs.Mini systems seem to induce at least an equal increased state of hypercoagulability after coronary surgery. No clinical relevant differences could be demonstrated. This could indicate that patients after using mini systems are not protected against a postoperative state of increased hypercoagulability.

This article presents a reconfigurable network-on-chip architecture called ReNoC, which is intended for use in general-purpose multiprocessor system-on-chip platforms, and which enables application-specific logical NoC topologies to be configured, thus providing both efficiency and flexibility. The article presents three novel algorithms that synthesize an application-specific NoC topology, map it onto the physical ReNoC architecture, and create deadlock-free, application-specific routing algorithms. We apply our algorithms to a mixture of real and synthetic applications and target three different physical architectures. Compared to a conventional NoC, ReNoC reduces power consumption by up to 58% on average.

The paper explores a recently developed method for statistical response load (load effect) extrapolation for application to extreme response of wind turbines during operation. The extrapolation method is based on average conditional exceedance rates and is in the present implementation restricted to cases where the Gumbel distribution is the appropriate asymptotic extreme value distribution. However, two extra parameters are introduced by which a more general and flexible class of extreme value distributions is obtained with the Gumbel distribution as a subclass. The general method is implemented within a hierarchical model where the variables that influence the loading are divided into ergodic variables and time-invariant non-ergodic variables. The presented method for statistical response load extrapolation was compared with the existing methods based on peak extrapolation for the blade out-of-plane bending moment and the tower mudline bending moment of a pitch-controlled wind turbine. In general, the results show that the method based on average conditional exceedance rates predicts the extrapolated characteristic response loads at the individual mean wind speeds well and results in more consistent estimates than the methods based on peak extrapolation. Copyright © 2011 John Wiley & Sons, Ltd.

In this paper, two stochastic models for the distribution of defects in wind turbine blades are proposed. The first model assumes that the individual defects are completely randomly distributed in the blade. The second model assumes that the defects occur in clusters of different size, based on the assumption that one error in the production process tends to trigger several defects. For both models, additional information, such as number, type, and size of the defects, is included as stochastic variables.In a numerical example, the reliability is estimated for a generic wind turbine blade model both with and without defects in terms of delaminations. The reliability of the blade decreases when defects are included. However, the distribution of the defects influences how much the reliability is decreased. It is also shown how non-destructive inspection (NDI) after production can be used to update the reliability for the wind turbine blade using Bayesian statistics. In this paper, two stochastic models for the distribution of defects in wind turbine blades are proposed. The first model assumes that the individual defects are completely randomly distributed in the blade. The second model assumes that the defects occur in clusters of different size, based on the assumption that one error in the production process tends to trigger several defects. For both models, additional information, such as number, type, and size of the defects, is included as stochastic variables.In a numerical example, the reliability is estimated for a generic wind turbine blade model both with and without defects in terms of delaminations. The reliability of the blade decreases when defects are included. However, the distribution of the defects influences how much the reliability is decreased. It is also shown how non-destructive inspection (NDI) after production can be used to update the reliability for the wind turbine blade using Bayesian statistics.

SUMMARYBeginning in 1970, the potential of remote sensing (RS) techniques, coupled with geographical information systems (GIS), to improve our understanding of the epidemiology and control of schistosomiasis in Africa, has steadily grown. In our current review, working definitions of RS, GIS and spatial analysis are given, and applications made to date with RS and GIS for the epidemiology and ecology of schistosomiasis in Africa are summarised. Progress has been made in mapping the prevalence of infection in humans and the distribution of intermediate host snails. More recently, Bayesian geostatistical modelling approaches have been utilized for predicting the prevalence and intensity of infection at different scales. However, a number of challenges remain; hence new research is needed to overcome these limitations. First, greater spatial and temporal resolution seems important to improve risk mapping and understanding of transmission dynamics at the local scale. Second, more realistic risk profiling can be achieved by taking into account information on people's socio-economic status; furthermore, future efforts should incorporate data on domestic access to clean water and adequate sanitation, as well as behavioural and educational issues. Third, high-quality data on intermediate host snail distribution should facilitate validation of infection risk maps and modelling transmission dynamics. Finally, more emphasis should be placed on risk mapping and prediction of multiple species parasitic infections in an effort to integrate disease risk mapping and to enhance the cost-effectiveness of their control.

Purpose: Human interleukin-21 (IL-21) is a class I cytokine that mediates activation of CD8+ T cells, natural killer (NK) cells, and other cell types. We report final clinical and biological results of a phase II study of recombinant human IL-21 (rIL-21) in patients with metastatic melanoma.Experimental Design: Open-label, single-arm, two-stage trial. Eligibility criteria: unresectable metastatic melanoma, measurable disease by Response Evaluation Criteria in Solid Tumors, no prior systemic therapy (adjuvant IFN permitted), adequate major organ function, good performance status, no significant autoimmune disease, and life expectancy at least 4 months. Primary objective: antitumor efficacy (response rate). Secondary objectives: safety, blood biomarkers, and generation of anti-rIL-21 antibodies. rIL-21 (30 μg/kg/dose) was administered by intravenous bolus injection in 8-week cycles (5 dosing days followed by 9 days of rest for 6 weeks and then 2 weeks off treatment).Results: Stage I of the study comprised 14 patients. One confirmed complete response (CR) was observed, and as per protocol, 10 more patients were accrued to stage II (total n = 24: 10 female and 14 male). Best tumor response included one confirmed CR and one confirmed partial response, both with lung metastases. Treatment was overall well tolerated. Biomarker analyses showed increases in serum soluble CD25, frequencies of CD25+ NK and CD8+ T cells, and mRNA for IFN-γ, perforin, and granzyme B in CD8+ T and NK cells.Conclusions: rIL-21 administered at 30 μg/kg/d in 5-day cycles every second week is biologically active and well tolerated in patients with metastatic melanoma. Confirmed responses, including one CR, were observed.

This investigation was carried out because of a clinical suspicion of drug interaction between Propoxyphene (PRX) hydrochloride and Carbamazepine (CBZ). Seven out-patients, six suffering from epilepsy and one from trigeminal neuralgia, treated with CBZ alone or in combination with phenobarbitone, received PRX hydrochloride capsules, 65 mg three times a day. Two patients stopped the PRX intake after 2 days due to severe side effects. Three of the remaining patients had symptoms and signs of drug intoxication. Blood samples were examined by thin-layer chromatography. A marked increase (45–77 per cent) in CBZ plasma level was found in all patients on combined treatment of CBZ and PRX. There were no significant changes in CBZ-10, 11-epoxide level. The results suggest an inhibition of CBZ metabolism when CBZ and PRX are administered simultaneously.

Interactions between analgesics and anti-epileptic drugs may sometimes present a serious clinical problem. The aim of the study was to investigate the influence of usually applied doses of dextropropoxyphene (DPX) on the steady state levels of carbamazepine (CBZ), phenytoin (DPH) and phenobarbital (PB). Sixteen patients in monotherapy completed the trial, while four patients dropped out. In patients on CBZ serum levels increased (mean appr. 66 %) after 6 days on DPX. In three of the patients a further increase was seen after an additional week on DPX. One patient discontinued the DPX intake because of clinical signs of toxicity, but the remainder were clinically unaffected. CBZ-epoxide levels declined simultaneously. For DPH only a doubtful increase was observed after 1–2 weeks on DPX. For PB an average increase of 20 % in serum level was noted after 1 week. The protein binding of CBZ and DPH was not affected. It is concluded that patients on CBZ should be treated only with DPX if monitored properly. Patients on DPH or PB should be followed carefully until further evidence has been produced.

Recombinant interleukin-21 (rIL-21) is an immune stimulating cytokine recently tested in two Phase 1 trials for immune responsive cancers. A secondary objective of these trials was to characterize pharmacodynamic responses to rIL-21 in patients. Here, we report the effects of systemic rIL-21 on serum markers of immune stimulation.Recombinant IL-21 was administered by intravenous bolus injection at dose levels from 1 to 100 microg/kg using two distinct treatment regimens: thrice weekly ('3/w') for 6 weeks; or once daily for five consecutive days followed by nine dose-free days ('5 + 9'). In the absence of dose limiting toxicity, additional cycles of dosing were initiated immediately following the nine dose-free days. An array of 70 different proteins was profiled in subject serum samples from several time points during the course of the study. Hierarchical clustering analysis was performed on a normalized subset of these data.Systemic administration of rIL-21 affected the serum levels of several cytokines, chemokines, acute-phase proteins and cell adhesion proteins. The magnitude and duration of response were dose dependent for a subset of these biomarkers. The 5 + 9 dosing regimen generally produced cyclic changes that were of greater magnitude, as compared to a more chronic stimulation with the 3/w dosing regimen. Despite these differences, rIL-21 effects on many analytes were similar between regimens when averaged over the time of treatment. Based on similar temporal, between-subject and dose response changes, groups of analytes were identified that exhibited distinct components of the rIL-21-mediated immune activation. Biomarkers indicative of lymphocyte activation (increased IL-16, decreased RANTES), acute phase response (increased CRP, ferritin), myeloid activation (increased MDC, MIP-1 alpha), and leukocyte chemotaxis/trafficking (increased sCAMs, MCP-1) were strongly modulated in subjects treated with rIL-21.Administration of rIL-21 resulted in activation of multiple cell types and immune response pathways. The changes observed in serum proteins were consistent with coincident processes of lymphoid and myeloid cell activation and trafficking, and acute phase response.

Background Inflammatory bowel disease (IBD) is a complex multi-factorial inflammatory disease with Crohn’s disease (CD) and ulcerative colitis (UC) being the two most common forms. A number of transcriptional profiling studies have provided compelling evidence that describe the role of protein-coding genes and microRNAs in modulating the immune responses in IBD. Methods In the present study, we performed a genome-wide transcriptome profiling of lncRNAs and protein-coding genes in 96 colon pinch biopsies (inflamed and non-inflamed) extracted from multiple colonic locations from 45 patients (CD = 13, UC = 20, controls = 12) using an expression microarray platform. Results In our study, we identified widespread dysregulation of lncRNAs and protein-coding genes in both inflamed and non-inflamed CD and UC compared to the healthy controls. In cases of inflamed CD and UC, we identified 438 and 745 differentially expressed lncRNAs, respectively, while in cases of the non-inflamed CD and UC, we identified 12 and 19 differentially expressed lncRNAs, respectively. We also observed significant enrichment (P-value

BACKGROUND: It is important to ensure that tools are valid and reliable in the context in which they are used. The development of age and country norms is part of this process.OBJECTIVES: The primary aim of the present study was to examine the performance of the Food Allergy Quality of Life Questionnaire - Parent Form (FAQLQ-PF) in a countrywide American sample of children with food allergy. The secondary aim was to compare age differences in impact across 9 European countries.METHODS: In a cross-sectional quantitative design, questionnaires were completed by the parents of 1029 food-allergic children (0-12 years). Participants were recruited via support groups and allergists. Data were analyzed by using multivariate analysis of variance and tests for internal consistency and validity. The average score was calculated for each age group in 15 studies in Ireland, Switzerland, the Netherlands, Spain, Portugal, Germany, Italy, Denmark, Israel, and the United Kingdom.RESULTS: The FAQLQ-PF has high convergent validity (child: r = 0.49, n = 695, P = .01; parent: r = 0.36, n = 696, P = .01) and discriminant validity, parent: t (719) = 4.67, P = .001 (anaphylaxis yes vs no); t (513), P = .009 (single vs multiple allergens). Internal consistency was excellent (r = 0.96). US health-related quality of life was worse than European health-related quality of life, as indicated by higher FAQLQ-PF scores in US samples. Burden increased with age in all populations.CONCLUSIONS: The FAQLQ-PF is appropriate for use in an American population. Findings will form the basis for further work in the development of an online manual with food allergy-normed age scores to allow for precise measurement, interpretation of scores, and comparison across countries and cultures, in clinical and research settings. (C) 2016 American Academy of Allergy, Asthma & Immunology

The reliability of offshore wind turbines is highly influenced by the uncertainties related to the subsoil conditions. Traditionally, the evaluation of the dynamic structural behaviour is based on a computational model with deterministic soil properties. Using this approach, however, provides limited insight into thevariation of the estimate of the inherent modal properties and loads. In this paper, a comprehensive study is performed on the dynamic behaviour of an offshore wind turbine installed on a monopile foundation. Based on consistent lumped-parameter models calibrated to semi-analytical impedance functions of a monopile embedded in a stochastic linear viscoelastic soil layer, fully coupled aero-hydro-elastic simulations are conducted in the nonlinear multi-body code HAWC2. The probabilistic analysis accounts for the uncertainty of soil properties (e.g. damping and stiffness) and relies on a Monte Carlo method facilitating the derivation of the probability densities of the modal properties and the fatigue loading. The main conclusion of the presented work is that the dynamic structural behaviour of the wind turbine and its support structure is strongly affected by the stochastic soil properties. Lognormal and Gumbel distributed modal damping and side-side fatigue damage equivalent moments with a coefficient of variation of 30% and 8%, respectively, are observed. The reliability of offshore wind turbines is highly influenced by the uncertainties related to the subsoil conditions. Traditionally, the evaluation of the dynamic structural behaviour is based on a computational model with deterministic soil properties. Using this approach, however, provides limited insight into the variation of the estimate of the inherent modal properties and loads. In this paper, a comprehensive study is performed on the dynamic behaviour of an offshore wind turbine installed on a monopile foundation. Based on consistent lumped-parameter models calibrated to semi-analytical impedance functions of a monopile embedded in a stochastic linear viscoelastic soil layer, fully coupled aero-hydro-elastic simulations are conducted in the nonlinear multi-body code Hawc2. The probabilistic analysis accounts for the uncertainty of soil properties (e.g. damping and stiffness) and relies on a Monte Carlo method facilitating the derivation of the probability densities of the modal properties and the fatigue loading. The main conclusion of the presented work is that the dynamic structural behaviour of the wind turbine and its support structure is strongly affected by the stochastic soil properties. Lognormal and Gumbel distributed modal damping and accumulated side–side fatigue damage equivalent moments with a coefficient of variation of 30% and 8%, respectively, are observed.

Background: Chlamydia is the most common bacterial sexually transmitted disease (STD) in adolescents, and may have severe consequences such as pelvic infections, cervical cancer and infertility if left untreated. Studies have determined that young people have several barriers towards getting tested for STD. This study seeks not only to address the barriers to STD testing but also to understand them and thereby improve the quality of care in an outpatient clinic and increase screening rates. Methods: The study uses a phenomenological, hermeneutical approach through qualitative interviews. Four focus groups with a total of 22 participants in the age between 16-25 years were conducted for this study. Results: It was found that testing for STD is still associated with stigmatization and our findings indicate that testing for STD should undergo normalization. At the same time health care providers face a major challenge in advising young people due to the lack of knowledge and the fear of being reprimanded. Conclusions: None of the participants were aware of our clinic. Changes were made in the outpatient clinic to consider the needs of the young people. We implemented non-invasive screening methods for those attending asymptomatic screening, introduced both nurse-led consultations and anonymous counseling regarding STDs and testing.

The purpose of this study was to determine whether visual stimulation in sleeping infants and young children can be examined by functional magnetic resonance imaging. We studied 17 children, aged 3 d to 48 mo, and three healthy adults. Visual stimulation was performed with 8-Hz flickering light through the sleeping childs' closed eyelids. Functional magnetic resonance imaging was performed with a gradient echoplanar sequence in a l.5-T magnetic resonance scanner. Six subjects were excluded because of movement artifacts; the youngest infant showed no response. In 10 children, we could demonstrate areas of signal decrease during visual stimulation in the occipital cortex (mean decrease 2.21%), contrary to the signal increase observed in the adult controls (mean increase 2.82%). This decrease may be due to a higher proportional increase in oxygen extraction compared with increase in cerebral blood flow during activation. The different response patterns in young children and adults can reflect developmental or behavioral differences. Localization of the activation seemed to be age-dependent. In the older children and the adults, it encompassed the whole length of the calcarine sulcus, whereas it was restricted to the anterior and medial part of the calcarine sulcus in the younger infants. This may reflect a different functional organization of the young child's visual cortex or the on-going retinal development.

Background Past case reports have indicated that lymphatic filariasis (LF) occurs in Zambia, but knowledge about its geographical distribution and prevalence pattern, and the underlying potential environmental drivers, has been limited. As a background for planning and implementation of control, a country-wide mapping survey was undertaken between 2003 and 2011. Here the mapping activities are outlined, the findings across the numerous survey sites are presented, and the ecological requirements of the LF distribution are explored. Methodology/Principal findings Approximately 10,000 adult volunteers from 108 geo-referenced survey sites across Zambia were examined for circulating filarial antigens (CFA) with rapid format ICT cards, and a map indicating the distribution of CFA prevalences in Zambia was prepared. 78% of survey sites had CFA positive cases, with prevalences ranging between 1% and 54%. Most positive survey sites had low prevalence, but six foci with more than 15% prevalence were identified. The observed geographical variation in prevalence pattern was examined in more detail using a species distribution modeling approach to explore environmental requirements for parasite presence, and to predict potential suitable habitats over unsurveyed areas. Of note, areas associated with human modification of the landscape appeared to play an important role for the general presence of LF, whereas temperature (measured as averaged seasonal land surface temperature) seemed to be an important determinant of medium-high prevalence levels. Conclusions/significance LF was found to be surprisingly widespread in Zambia, although in most places with low prevalence. The produced maps and the identified environmental correlates of LF infection will provide useful guidance for planning and start-up of geographically targeted and cost-effective LF control in Zambia., Author Summary Lymphatic filariasis (LF) is a debilitating mosquito borne parasitic infection which worldwide affects more than 120 million people. It is also widespread in Sub-Saharan Africa. A World Health Organization coordinated Global Programme to Eliminate LF has targeted LF for elimination as a public health problem by the year 2020, with annual mass drug administration (MDA) being the primary measure for this endeavor. An important first step before initiating MDA is the geographical mapping of infection in order to delimit the target areas. Past case reports have indicated that LF occurs in Zambia, but knowledge on its distribution and prevalence has been limited. Here we report on a country-wide survey carried out to map the geographical distribution and prevalence pattern across Zambia by screening adult volunteers for specific circulating filarial antigens (CFA). The CFA prevalences observed at the numerous survey sites are presented and mapped to give an indication of LF distribution in the country. The observed geographical variation is furthermore examined using a species distribution modeling approach to explore environmental requirements for LF presence, and to predict potential suitable habitats over unsurveyed areas. The findings provide a firm background for planning and start-up of LF control in Zambia.

We deliver a design flow for the synthesis and convergence of application-specific networks-on-chip. The flow comes with novel features that can better address nanoscale design challenges: front-end driven floorplanning, dynamic IR-drop minimization, fast and accurate system-level power grid modeling, predictable link design. Above all, such features are addressed by different prototype engines, even from different vendors, that can be smoothly integrated into the flow by means of a common specification format called Communication Exchange Format (CEF), that enables unprecedented tool interactions. This flow is validated by means of an extensive demonstration framework.

This paper discusses actions which the British Columbia Ferry Corporation has undertaken subsequent to the catastrophic 1994 Estonia capsize accident in the Baltic Sea that resulted in the loss of 912 lives. The corporation sets as its highest goal the provision of a "safe, efficient and effective ferry system," and therefore the actions described form part of a continuum of safety improvement which is central to the BCFC operating philosophy. Recommendations with respect to both rough water, northern route vessels and to the southern route, more sheltered water fleet are outlined. In addition, the improvement of safety on the northern routes vessels by the fitting of improved supporting and closing devices on the bow visors, by improving the bow ramp securing arrangements and by installation of inner weathertight doors is described in detail. Some recent model testing undertaken to investigate the potential for "bow scooping," and which has provided valuable input to the International Maritime Organization's Panel of Experts in determining the limits of application of proposed bow flooding criteria, is reviewed.

In the present paper a probabilistic model for fatigue crack growth in welded steel details in road bridges is presented. The probabilistic model takes the influence of bending stresses in the joints into account. The bending stresses can either be introduced by e.g. misalignment or redistribution of stresses in the structure. The fatigue stress ranges are estimated from traffic measurements and a generic bridge model. Based on the probabilistic models for the resistance and load the reliability is estimated for a typical welded steel detail. The results show that large misalignments in the joints can have a significant influence on the reliability level. In the present paper a probabilistic model for fatigue crack growth in welded steel details in road bridges is presented. The probabilistic model takes the influence of bending stresses in the joints into account. The bending stresses can either be introduced by e.g. misalignment or redistribution of stresses in the structure. The fatigue stress ranges are estimated from traffic measurements and a generic bridge model. Based on the probabilistic models for the resistance and load the reliability is estimated for a typical welded steel detail. The results show that large misalignments in the joints can have a significant influence on the reliability level.

In structures submitted to repeated variable loads, initiation and growth of cracks in the material are one of the most common causes of the deterioration of structures, especially in combination with corrosion. Under variable amplitude and repeated loads, some local cracks initiate on critical points of the structures, develop into critical cracks and failure due to fatigue.Many parameters used for predicting times to failure of structure due to fatigue are uncertain and their variations have a big influence on the real lifetime. This paper will focus on a global methodology to take into account main sources of variability in fatigue prediction for stay cables in cable stayed bridges. The first step of this methodology is to model the variability of each parameter. Loading is one of the most important sources of variability. Another important source of variability is the fatigue strength of the material. Probabilistic Wöhler curves are fitted using available data, and used to represent the variability of material fatigue behaviour. Finally, the reliability is assessed using Monte Carlo simulations.

Gene expression signatures can provide an unbiased view into the molecular changes underlying biologically and medically interesting phenotypes. We therefore initiated this study to identify signatures that would be of utility in studying rheumatoid arthritis (RA). We used microarray profiling of peripheral blood mononuclear cells (PBMCs) in 30 RA patients to assess the effect of different biologic agent (biologics) treatments and to quantify the degree of a type-I interferon (IFN) signature in these patients. A numeric score was derived for the quantification step and applied to patients with RA. To further characterize the IFN response in our cohort, we employed type-I IFN treatment of PBMCs in vitro and in reporter assays. Profiling identified a subset of RA patients with upregulation of type-I IFN-regulated transcripts, thereby corroborating previous reports showing RA to be heterogeneous for an IFN component. A comparison of individuals currently untreated with a biologic with those treated with infliximab, tocilizumab, or abatacept suggested that each biologic induces a specific gene signature in PBMCs. It is possible to observe signs of type-I IFN pathway activation in a subset of clinically active RA patients without C-reactive protein elevation. Furthermore, biologics-specific gene signatures in patients with RA indicate that looking for a biologic-specific response pattern may be a potential future tool for predicting individual patient response.

Chronic eczematous hand dermatoses with and without contact allergies are complex diseases, which makes it a challenge to select the best treatment and obtain an optimal patient experience and a satisfactory treatment result. The aim of this study was to evaluate retrospectively the clinical effect and patient experience of local treatment with psoralen plus ultraviolet A (PUVA) soaks and TL01 phototherapy for severe chronic hand dermatoses, and also to evaluate the quality of life for the subgroup of patients with allergic contact dermatitis including Compositae allergy. A retrospective evaluation of results for 94 consecutive patients having received a total of 121 treatment courses with local PUVA soaks or TL01 phototherapy for one of the following diagnoses (n=number of treatment courses): psoriasis (n=19), hyperkeratotic hand eczema (n=27), Pustulosis Palmoplantaris (PPP) (n=22), vesicular eczema (n=16), Compositae dermatitis (n=24), and allergic contact dermatitis (n=13). Moreover, semi-structured interviews with 6 selected patients having multiple contact allergies including Compositae allergy were used to evaluate quality of life. As a result, we found that PUVA soaks has good effect in patients with psoriasis and hyperkeratotic hand eczema and local phototherapy for chronic hand dermatoses is a useful treatment option in selected cases.

A probabilistic model for the reliability analysis of adhesive bonded scarfed lap joints subjected to static loading is developed. It is representative for the main laminate in a wind turbine blade subjected to flapwise bending. The structural analysis is based on a three dimensional (3D) finite element analysis (FEA). For the reliability analysis a design equation is considered which is related to a deterministic code-based design equation where reliability is secured by partial safety factors together with characteristic values for the material properties and loads. The failure criteria are formulated using a von Mises, a modified von Mises and a maximum stress failure criterion. The reliability level is estimated for the scarfed lap joint and this is compared with the target reliability level implicitly used in the wind turbine standard IEC 61400-1. A convergence study is performed to validate the FEA model, and a sensitivity analysis on the influence of various geometrical parameters and material properties on the maximum stress is conducted. Because the yield behavior of many polymeric structural adhesives is dependent on both deviatoric and hydrostatic stress components, different ratios of the compressive to tensile adhesive yield stresses in the failure criterion are considered. It is shown that the chosen failure criterion, the scarf angle and the load are significant for the assessment of the probability of failure.

Background After many years of general neglect, interest has grown and efforts came under way for the mapping, control, surveillance, and eventual elimination of neglected tropical diseases (NTDs). Disease risk estimates are a key feature to target control interventions, and serve as a benchmark for monitoring and evaluation. What is currently missing is a georeferenced global database for NTDs providing open-access to the available survey data that is constantly updated and can be utilized by researchers and disease control managers to support other relevant stakeholders. We describe the steps taken toward the development of such a database that can be employed for spatial disease risk modeling and control of NTDs. Methodology With an emphasis on schistosomiasis in Africa, we systematically searched the literature (peer-reviewed journals and ‘grey literature’), contacted Ministries of Health and research institutions in schistosomiasis-endemic countries for location-specific prevalence data and survey details (e.g., study population, year of survey and diagnostic techniques). The data were extracted, georeferenced, and stored in a MySQL database with a web interface allowing free database access and data management. Principal Findings At the beginning of 2011, our database contained more than 12,000 georeferenced schistosomiasis survey locations from 35 African countries available under http://www.gntd.org. Currently, the database is expanded to a global repository, including a host of other NTDs, e.g. soil-transmitted helminthiasis and leishmaniasis. Conclusions An open-access, spatially explicit NTD database offers unique opportunities for disease risk modeling, targeting control interventions, disease monitoring, and surveillance. Moreover, it allows for detailed geostatistical analyses of disease distribution in space and time. With an initial focus on schistosomiasis in Africa, we demonstrate the proof-of-concept that the establishment and running of a global NTD database is feasible and should be expanded without delay., Author Summary There is growing interest in the scientific community, health ministries, and other organizations to control and eventually eliminate neglected tropical diseases (NTDs). Control efforts require reliable maps of NTD distribution estimated from appropriate models and survey data on the number of infected people among those examined at a given location. This kind of data is often available in the literature as part of epidemiological studies. However, an open-access database compiling location-specific survey data does not yet exist. We address this problem through a systematic literature review, along with contacting ministries of health, and research institutions to obtain disease data, including details on diagnostic techniques, demographic characteristics of the surveyed individuals, and geographical coordinates. All data were entered into a database which is freely accessible via the Internet (http://www.gntd.org). In contrast to similar efforts of the Global Atlas of Helminth Infections (GAHI) project, the survey data are not only displayed in form of maps but all information can be browsed, based on different search criteria, and downloaded as Excel files for further analyses. At the beginning of 2011, the database included over 12,000 survey locations for schistosomiasis across Africa, and it is continuously updated to cover other NTDs globally.

Probabilistic design of wind turbines requires definition of the structural elements to be included in the probabilistic basis: e.g., blades, tower, foundation; identification of important failure modes; careful stochastic modeling of the uncertain parameters; recommendations for target reliability levels and recommendation for consideration of system aspects. The uncertainties are characterized as aleatoric (physical uncertainty) or epistemic (statistical, measurement and model uncertainties). Methods for uncertainty modeling consistent with methods for estimating the reliability are described. It is described how uncertainties in wind turbine design related to computational models, statistical data from test specimens, results from a few full-scale tests and from prototype wind turbines can be accounted for using the Maximum Likelihood Method and a Bayesian approach. Assessment of the optimal reliability level by cost-benefit optimization is illustrated by an offshore wind turbine example. Uncertainty modeling is illustrated by an example where physical, statistical and model uncertainties are estimated. Probabilistic design of wind turbines requires definition of the structural elements to be included in the probabilistic basis: e.g., blades, tower, foundation; identification of important failure modes; careful stochastic modeling of the uncertain parameters; recommendations for target reliability levels and recommendation for consideration of system aspects. The uncertainties are characterized as aleatoric (physical uncertainty) or epistemic (statistical, measurement and model uncertainties). Methods for uncertainty modeling consistent with methods for estimating the reliability are described. It is described how uncertainties in wind turbine design related to computational models, statistical data from test specimens, results from a few full-scale tests and from prototype wind turbines can be accounted for using the Maximum Likelihood Method and a Bayesian approach. Assessment of the optimal reliability level by cost-benefit optimization is illustrated by an offshore wind turbine example. Uncertainty modeling is illustrated by an example where physical, statistical and model uncertainties are estimated.

Abstract The Kikeh Development is the first deepwater project in Malaysia located Offshore Eastern Malaysia in the South China Sea with a water depth of 1320 m. Kikeh is produced via a Spar and a subsea water injection and production system back to a Floating Production Storage and Offloading (FPSO) unit (see Figure 1). Kikeh is planned to be developed using 34 wells and initial production commenced in August 2007. The main subsea installation portion of the Kikeh development was executed through an Engineering, Procurement, Construction, Installation, and Commissioning Support contract with Technip Marine (Malaysia) Sdn Bhd. The installation scope of work included the following:5 manifold support piles*5 subsea manifolds*5 flexible risers and flowlines with a total length of over 31 km of flexible pipe7 riser holdback anchor piles4 electro-hydraulic control (EHC) umbilicals (2 dynamic/static and 2 infield static)*5 rigid spools c/w vertical connection module (VCM) clamp connectors (out of 14 in total)*5 subsea distribution units*6 hydraulic flying leads (out of 27 in total)*6 electrical flying leads (out of 48 in total)*Pre-commissioning of the subsea systems * Free issued from subsea equipment EPCC contractor The paper will discuss the process of offshore installation vessel selection including the effects on the decision process of utilizing local equipment versus mobilizing deepwater construction equipment from other deepwater basins around the world. In addition, with deepwater Sabah being a greenfield deepwater basin, a number of challenges arose in relation to availability of equipment within the region and logistics to support the deepwater construction operations. Highlights from Phase I, Phase II, and Phase III installation programs are also presented.

This paper presents a network-on-chip (NoC) architecture that enables the network topology to be reconfigured. The architecture thus enables a generalized System.-on-Chip (SoC) platform in which the topology can be customized for the application that is currently running on the chip, including long links and direct links between IP-blocks. The configurability is inserted as a layer between routers and links, and the architecture can therefore be used in combination with existing NoC routers, making it a general architecture. The topology is configured using energy-efficient topology switches based on physical circuit-switching as found in FPGAs. The paper presents the ReNoC (Reconfigurable NoC) architecture and evaluates its potential. The evaluation design shows a 56% decrease in power consumption compared to a static 2D mesh topology.

A large number of databases are currently being implemented within toxicology aiming to integrate diverse biological data, such as clinical chemistry, expression, and other types of data. However, for these endeavors to be successful, tools for integration, visualization, and interpretation are needed. This paper presents a method for data integration using a hierarchical model based on either principal component analysis or partial least squares discriminant analysis of clinical chemistry, expression, and nuclear magnetic resonance data using a toxicological study as case. The study includes the three toxicants alpha-naphthyl-isothiocyanate, dimethylnitrosamine, and N-methylformamide administered to rats. Improved predictive ability of the different classes is seen, suggesting that this approach is a suitable method for data integration and visualization of biological data. Furthermore, the method allows for correlation of biological parameters between the different data types, which could lead to an improvement in biological interpretation.

Purpose: Human interleukin-21 (IL-21) is a pleiotropic class I cytokine that activates CD8+ T cells and natural killer cells. We report a phase 1 study of recombinant human IL-21 in patients with surgically incurable metastatic melanoma. The primary objective was to investigate safety and tolerability by determining dose-limiting toxicity (DLT). The secondary objectives were to identify a dose response for various biomarkers in the peripheral blood, estimate the minimum biologically effective dose, determine the pharmacokinetics of IL-21, determine if anti-IL-21 antibodies were induced during therapy, and measure effects on tumor size according to Response Evaluation Criteria in Solid Tumors.Experimental Design: Open-label, two-arm, dose escalation trial of IL-21 administered by i.v. bolus injection at dose levels from 1 to 100 μg/kg using two parallel treatment regimens: thrice weekly for 6 weeks (3/wk) or three cycles of daily dosing for 5 days followed by 9 days of rest (5+9).Results: Twenty-nine patients entered the study. IL-21 was generally well tolerated and no DLTs were observed at the 1, 3, and 10 μg/kg dose levels. In the 3/wk regimen, DLTs were increased in alanine aminotransferase, neutropenia, and lightheadedness with fever and rigors. DLTs in the 5+9 regimen were increased in aspartate aminotransferase and alanine aminotransferase, neutropenia, fatigue, and thrombocytopenia. The maximum tolerated dose was declared to be 30 μg/kg for both regimens. Effects on biomarkers were observed at all dose levels, including increased levels of soluble CD25 and up-regulation of perforin and granzyme B mRNA in CD8+ cells. One partial tumor response observed after treatment with IL-21 for 2 × 6 weeks (3/wk) became complete 3 months later.Conclusions: IL-21 is biologically active at all dose levels administered and is generally well tolerated, and phase 2 studies have commenced using 30 μg/kg in the 5+9 regimen.