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Background People with type 1 diabetes can continuously monitor their glucose levels on demand (intermittently scanned continuous glucose monitoring [isCGM]), or in real time (real-time continuous glucose monitoring [rtCGM]). However, it is unclear whether switching from isCGM to rtCGM with alert functionality offers additional benefits. Therefore, we did a trial comparing rtCGM and isCGM in adults with type 1 diabetes (ALERTT1). Methods We did a prospective, double-arm, parallel-group, multicentre, randomised controlled trial in six hospitals in Belgium. Adults with type 1 diabetes who previously used isCGM were randomly assigned (1:1) to rtCGM (intervention) or isCGM (control). Randomisation was done centrally using minimisation dependent on study centre, age, gender, glycated haemoglobin (HbA(1c)), time in range (sensor glucose 3.9-10.0 mmol/L), insulin administration method, and hypoglycaemia awareness. Participants, investigators, and study teams were not masked to group allocation. Primary endpoint was mean between-group difference in time in range after 6 months assessed in the intention-to-treat sample. This trial is registered with ClinicalTrials.gov, NCT03772600. Findings Between Jan 29 and July 30, 2019, 269 participants were recruited, of whom 254 were randomly assigned to rtCGM (n=127) or isCGM (n=127); 124 and 122 participants completed the study, respectively. After 6 months, time in range was higher with rtCGM than with isCGM (59.6% vs 51.9%; mean difference 6.85 percentage points [95% CI 4.36-9.34]; p

Background and Purpose: Lacunar syndromes correlate with a lacunar stroke on imaging in 50% to 60% of cases. Computed tomography perfusion (CTP) is becoming the preferred imaging modality for acute stroke triage. We aimed to estimate the sensitivity, specificity, and predictive values for noncontrast computed tomography and CTP in lacunar syndromes, and for cortical, subcortical, and posterior fossa regions. Methods: A retrospective analysis of confirmed ischemic stroke patients who underwent acute CTP and follow-up magnetic resonance imaging between 2010 and 2018 was performed. Brain noncontrast computed tomography and CTP were assessed independently by 2 stroke neurologists. Receiver operating characteristic curve analysis was performed to estimate sensitivity, specificity, and area under the curve (AUC) for the detection of strokes in patients with lacunar syndromes using different CTP maps. Results: We found 106 clinical lacunar syndromes, but on diffusion-weighted imaging, these consisted of 59 lacunar, 33 cortical, and 14 posterior fossa strokes. The discrimination of ischemia identification was very poor using noncontrast computed tomography in all 3 regions, but good for cortical (AUC, 0.82) and poor for subcortical and posterior regions (AUCs, 0.55 and 0.66) using automated core-penumbra maps. The addition of delay time and mean transient time maps substantially increased subcortical (AUC, 0.80) and slightly posterior stroke detection (AUC, 0.69). Conclusions: Analysis of mean transient time and delay time maps in combination with core-penumbra maps improves detection of subcortical and posterior strokes.

Background In many countries, men who have sex with men (MSM) using pre-exposure prophylaxis (PrEP) are routinely three-monthly tested and treated for Neisseria gonorrhoeae (gonorrhoea), which might increase antimicrobial resistance (AMR). However, there is uncertainty about how AMR emerges. We investigated the impact of frequent testing and treating on gonorrhoea prevalence and AMR assuming different ways of AMR emergence. Methods We developed a compartmental model, which included three sexual activity classes that differed in unprotected sex partner numbers and testing uptake. AMR to ceftriaxone was incorporated as stepwise increases in minimum inhibitory concentrations and eventual resistance (MIC drift) in three separate ways: direct selection pressure through ceftriaxone treatment; indirect selection pressure through antimicrobials treatment for other reasons; or imported infection. Each model was calibrated to the ceftriaxone MIC curve from the Dutch Gonococcal Resistance to Antimicrobials Surveillance program (2015–2019). We estimated the impact of three-monthly testing of high-risk MSM on overall and AMR prevalence in 2030. Results Overall gonorrhoea model prevalence was 3.4% (95% uncertainty interval 3.2%–3.5%), and 14.3% (11.7%–18.0%) in high-risk MSM. Three-monthly testing resulted in 66%–93% reductions in overall prevalence for all three ways in which AMR development was modelled. AMR prevalence was low in 2030 for all three mechanisms, but increased fastest with direct selection compared to indirect or imported. With direct selection, AMR prevalence was 1.7 (1.3–2.0) times higher than with indirect selection and 8.2 (2.7–16.1) times higher than through imported infection. When high-risk MSM increased numbers of unprotected sex partners, three-monthly testing reduced overall prevalence less and AMR prevalence increased, especially with direct selection. Conclusion With frequent testing of MSM, direct selection pressure through treatment leads to more gonococcal resistance than indirect selection or imported infection. This study highlights the need to increase our understanding of mechanisms of AMR emergence in N. gonorrhoeae.

In many work domains, the push toward higher levels of automation raises the concern of diminishing human expertise. Ecological interfaces could help operators in retaining and potentially even in acquiring expertise as they are hypothesized to lead to a deeper understanding of the work domain. This study explores the short-term impact of ecological interfaces on knowledge development and compares the results with an instruction-based training method. To monitor and compare students' progress, their decision-making strategies, identified from verbal comments recorded in 'think-aloud' simulator sessions, are mapped onto the decision ladder. This method has been applied to an experiment (N=16) aimed at training novices in conflict detection and resolution (CD&R) within a simplified air traffic control context. Results show that the overall CD&R performance in the final measurement sessions, featuring a transfer manipulation, was not significantly different between the 'ecological' and 'instructional' groups. In terms of cognitive behavior, however, students in the ecological group exhibited more laborious rule- and knowledge-based behaviors that sparked goal-oriented thoughts and corresponding control performances beyond the CD&R task. These findings indicate that ecological interfaces can change how people think and approach a control problem, even after removing the support. It is therefore reasonable to believe that ecological interfaces can play an important role in the early stages of deep knowledge development.

Background: Upper limb (UL) hemiparesis is a common, disabling and persistent problem, and a major contributor to poor well-being and quality of life in persons after stroke. Conventional U...

Background and Purpose— Poststroke fatigue affects a large proportion of stroke survivors and is associated with a poor quality of life. In a recent trial, modafinil was shown to be an effective agent in reducing poststroke fatigue; however, not all patients reported a significant decrease in fatigue with therapy. We sought to investigate clinical and radiological predictors of fatigue reduction with modafinil therapy in a stroke survivor cohort. Methods— Twenty-six participants with severe fatigue (multidimensional fatigue inventory–20 ≥60) underwent magnetic resonance imaging at baseline and during the last week of a 6-week treatment period of 200 mg modafinil taken daily. Resting-state functional magnetic resonance imaging and high-resolution structural imaging data were obtained, and functional connectivity and regional brain volumes within the fronto-striato-thalamic network were obtained. Linear regression analysis was used to identify predictors of modafinil-induced fatigue reduction. Results— Multiple regression analysis showed that baseline multidimensional fatigue inventory–20 score (β=0.576, P =0.006) and functional connectivity between the dorsolateral prefrontal cortex and the caudate nucleus (β=−0.424, P =0.008) were significant predictors of modafinil-associated decreases in poststroke fatigue (adjusted r 2 =0.52, area under the receiver operator characteristic curve=0.939). Conclusions— Fronto-striato-thalamic functional connectivity predicted modafinil response for poststroke fatigue. Fatigue in other neurological disease has been attributed to altered function of the fronto-striato-thalamic network and may indicate that poststroke fatigue has a similar mechanism to other neurological injury related fatigue. Self-reported fatigue in patients with normal fronto-striato-thalamic functional connectivity may have a different mechanism and require alternate therapeutic approaches. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: ACTRN12615000350527.

Background and Purpose: Altered executive functions and resting-state functional connectivity (rsFC) are common following a minor stroke or transient ischemic attack (TIA). However, the long-term persistence of these abnormalities is not well-studied. We investigated whether there were cognitive and rsFC differences between (a) controls and minor cerebrovascular event (CVE) patients and (b) between CVE patients with and without an imaging confirmed infarct (i.e., minor stroke and TIA, respectively) at an average of 3.8 years following their event.Methods: Structural and resting-state imaging and cognitive assessments including the Montreal Cognitive Assessment, the Trail Making Task and the National Institute of Health (NIH) Cognition Toolbox were conducted on 42 patients (minor stroke = 17, TIA = 25) and 20 healthy controls (total N = 62).Results: Controls performed better than patients on two measures of executive functioning (both p < 0.046) and had reduced rsFC between the frontoparietal and default mode networks (FPN and DMN, respectively; p = 0.035). No cognitive differences were found between minor stroke and TIA patients, however, rsFC differences were found within the FPN and the DMN (both p < 0.013). Specifically, increased connectivity within the FPN was associated with faster performance in the minor stroke group but not the TIA group (p = 0.047).Conclusions: These findings suggest that transient or relatively minor cerebrovascular events are associated with persistent disruption of functional connectivity of neural networks and cognitive performance. These findings suggest a need for novel interventions beyond secondary prevention to reduce the risk of persistent cognitive deficits.

The fabrication of a foldable, compact liquid crystal actuator based on oxetane reactive monomers is reported. The free-standing liquid crystal network films are optically clear, flexible, and have easily tunable anisotropic thermal and mechanical properties. The oxetane liquid crystal networks demonstrate excellent one-way shape memory properties, with good temporary shape fixation and complete shape recovery. In addition, the flexible polyether backbone of the oxetane liquid crystal networks results in large two-way bending actuation, with the actuators showing rotation inversion and making multiple rotations. Both actuation mechanisms could be combined to form actuators that can be temporarily folded before fully recovering to their original shape prior to use. As a result, the oxetane liquid crystal networks have greatpotential as foldable, compact actuators.

Objective The VASE-(M)HC is an instrument to evaluate Motivational Interviewing (MI) skills. We adjusted the previous version for use in the broader (mental) healthcare context, incorporated new MI insights, expanded the scoring system and created a parallel version. Feasibility and validity evidence in the general practice setting was explored. Methods The teaching staff of the GP specialty-training, GP-, and PN-trainees (N = 156) completed the VASE-(M)HC. In this mixed-methods study, we examined psychometric characteristics, compared parallel versions, and interviewed assessors. Results Our adjustments enable assessment of a wider range of MI skills, and allow differentiation of basic and advanced skills. Inter-rater reliability was excellent and internal consistency of the total scale was good for both versions. The parallel versions are comparable in terms of difficulty. Conclusion The VASE-(M)HC is improved by our revisions and adds multiple advantages to the domain of available MI assessment tools. Practice implications Due to the adjustments, the instrument can be used in the GP setting (instead of sole focus on substance abuse). The parallel version is useful for research (pretest/posttest) and selective assessment (retake of a test). It is promising to further explore its applicability in the broader (mental) healthcare context and as training material.

ObjectivesTrust plays an important role in workplace-based postgraduate medical education programmes. Trainers must trust their trainees for granting them greater independence. Trainees must trust their trainer for a safe learning environment. As trainers’ and trainees’ trust in each other plays an important role in trainee learning and development, the authors aimed to explore the development of the mutual trust relationship between trainers and trainees.SettingThis study was performed in a general practice training department in the Netherlands.ParticipantsAll trainers and trainees of the general practice training department were invited to participate. Fifteen trainers and 34 trainees, voluntarily participated in focus group discussions.Outcome measuresThe authors aimed to gain insight in the factors involved in the development of the mutual trust relationship between trainers and trainees, in order to be able to create a model for the development of a mutual trust relationship between trainers and trainees. The risk-based view of trust was adopted as leading conceptual framework.ResultsIn the first stage of trust development, trainers and trainees develop basic trust in each other. Basic trust forms the foundation of the trust relationship. In the second stage, trainers develop trust in trainees taking into account trainees’ working and learning performance, and the context in which the work is performed. Trainees trust their trainer based on the trainer’savailability and accessibility and the personal relationship between the trainee and their trainer. Trainee self-confidence modifies the development of a trust relationship.ConclusionThe development of a mutual trust relationship between trainers and trainees is a complex process that involves various stages, goals, factors and interactive aspects. As the mutual trust relationship influences the learning environment for trainees, greater emphasis on the mutual trust relationship may improve learning outcomes. Further research may explore the effect of long-term and short-term educational relationships on the trust relationship between trainers and trainees.

Deltaic and coastal ecosystems are changing in response to natural and anthropogenic forces that require ecosystem-level restoration efforts to avoid habitat degradation or loss. Models that link ecosystem components of hydrodynamics, morphodynamics, nutrient and vegetation dynamics to represent essential processes and feedbacks are advancing the field of environmental modeling and are vital to inform coastal restoration decisions. An Integrated Biophysical Model was developed by creating a new vegetation dynamics component and linking it to other primary ecosystem components that included essential feedbacks. The model performance was evaluated by applying it to a deltaic ecosystem that included marshes and estuaries. The Integrated Biophysical Model output captured the general temporal and spatial environmental trends of key variables. This integrated model is capable to perform long-term simulations to assess responses of deltaic and coastal systems to global change scenarios and can be used to inform restoration strategies in ecosystems worldwide.

BACKGROUND AND PURPOSE: Degeneration of gray matter and subcortical structures after ischemic stroke has been well described. However, little is known about white matter degeneration after stroke. It is unclear whether white matter degeneration occurs throughout the whole brain, or whether patterns of degeneration occur more in specific brain areas. METHODS: We prospectively collected National Institutes of Health Stroke Scale (NIHSS) scores and diffusion tensor imaging (DTI) in patients with acute ischemic stroke within the first week after onset (baseline), and at 1 and 3 months. DTI was processed to produce maps of fractional anisotropy, apparent diffusion coefficients, and axial and radial diffusivity. DTI parameters in specified regions-of-interest corresponding to items on the NIHSS were calculated and changes over time were assessed using linear mixed-effect modeling. RESULTS: Seventeen patients were included in the study. Mean age (SD) was 71 (11.7) years, and median (IQR) baseline NIHSS 9 (5-13.3). Changes over time were observed in both visual cortices, contralesional primary motor cortex, premotor cortex, and superior temporal gyrus (P < .05). Changes in the ipsilesional motor cortex and inferior parietal lobule were only seen in patients with scores on the respective NIHSS-items (P .05). CONCLUSION: White matter changes after stroke may be localized rather than a global phenomenon.

Electrochromic displays are among the key components of smart tags and their performance, defined by the color switch time, is directly linked to the level of humidity inside the displays. A time-efficient procedure, based on the use of a gravimetric moisture analyzer, was implemented, where the water content in a display could be related to the temperature and relative humidity of the manufacturing environment. The electrical performance of the displays was evaluated by measuring current as a function of time during voltage pulses of 4 s as these measurements quantified the time needed for color switch (should be < 1 s). The electrical performance was also measured as a function of the temperature and relative humidity of the manufacturing environment. By varying the temperature and the relative humidity systematically and measuring water content and display performance, a correlation between water content, switch time and manufacturing environment could be established and a safe range for manufacturing conditions could be found.

Motor function may be enhanced if aerobic exercise is paired with motor training. One potential mechanism is that aerobic exercise increases levels of brain-derived neurotrophic factor (BDNF), which is important in neuroplasticity and involved in motor learning and motor memory consolidation. This study will examine the feasibility of a parallel-group assessor-blinded randomised controlled trial investigating whether task-specific training preceded by aerobic exercise improves upper limb function more than task-specific training alone, and determine the effect size of changes in primary outcome measures. People with upper limb motor dysfunction after stroke will be allocated to either task-specific training or aerobic exercise and consecutive task-specific training. Both groups will perform 60 hours of task-specific training over 10 weeks, comprised of 3 × 1 hour sessions per week with a therapist and 3 × 1 hours of home-based self-practice per week. The combined intervention group will also perform 30 minutes of aerobic exercise (70–85%HRmax) immediately prior to the 1 hour of task-specific training with the therapist. Recruitment, adherence, retention, participant acceptability, and adverse events will be recorded. Clinical outcome measures will be performed pre-randomisation at baseline, at completion of the training program, and at 1 and 6 months follow-up. Primary clinical outcome measures will be the Action Research Arm Test (ARAT) and the Wolf Motor Function Test (WMFT). If aerobic exercise prior to task-specific training is acceptable, and a future phase 3 randomised controlled trial seems feasible, it should be pursued to determine the efficacy of this combined intervention for people after stroke. Keywords: Stroke, Motor function, Aerobic exercise, Task-specific training

Estetrol (E4) is an estrogen produced exclusively by the human fetal liver during pregnancy. In this study the pharmacodynamic effects of escalating doses of E4 in postmenopausal women were investigated.This was a partly randomized, open-label, multiple-rising-dose study in 49 postmenopausal women. Participants were randomized to receive either 2 mg E4 or 2 mg estradiol-valerate (E2 V) for 28 days. Subsequent dose-escalation groups were (non-randomized): 10, 20 and 40 mg E4. Blood samples were collected regularly for measuring endocrine and hemostasis variables, lipids and lipoproteins, fasting glucose and bone turnover markers.Estetrol treatment resulted in a decrease of follicle-stimulating hormone and luteinizing hormone and an increase of sex-hormone binding globulin. Changes in hemostasis variables were small. A lowering effect on low-density lipoprotein cholesterol was accompanied with an increase in high-density lipoprotein cholesterol and no or minimal changes in triglycerides. The considerable decrease in osteocalcin levels in the three highest E4 dose groups and the small decrease in C-telopeptide levels were comparable to the E2 V control group and suggest a preventive effect on bone loss. All changes observed were dose-dependent.In this study, estetrol treatment showed dose-dependent estrogenic effects on endocrine parameters, bone turnover markers, and lipids and lipoproteins. The effect on triglycerides was small as were the effects on hemostatic variables. These results support the further investigation of estetrol as a candidate for hormone therapy. Quantitatively, the effects of 10 mg estetrol were similar to the study comparator 2 mg estradiol valerate.

Background: The number of refugees is the highest ever worldwide. Many have experienced trauma in home countries or on their escape which has mental health sequelae. Intrusive memories comprise distressing scenes of trauma which spring to mind unbidden. Development of novel scalable psychological interventions is needed urgently. Aims: We propose that brief cognitive science-driven interventions should be developed which pinpoint a focal symptom alongside a means to monitor it using behavioural techniques. The aim of the current study was to assess the feasibility and acceptability of the methodology required to develop such an intervention. Method: In this study we recruited 22 refugees (16–25 years), predominantly from Syria and residing in Sweden. Participants were asked to monitor the frequency of intrusive memories of trauma using a daily diary; rate intrusions and concentration; and complete a 1-session behavioural intervention involving Tetris game-play via smartphone. Results: Frequency of intrusive memories was high, and associated with high levels of distress and impaired concentration. Levels of engagement with study procedures were highly promising. Conclusions: The current work opens the way for developing novel cognitive behavioural approaches for traumatized refugees that are mechanistically derived, freely available and internationally scalable.

Firms and economic policy makers need an enhanced understanding of universities, in terms of what academics value and how they interact, if they are to enhance collaboration around the generation and transfer of knowledge and technology between universities and industry. The literature increasingly focuses on identifying incentives and barriers within universities, but is largely limited to contexts in Europe and the USA, and favours individual over institutional determinants. The paper contributes by situating university–industry linkages within the total pattern of academic interaction with external actors, in diverse types of institutions. Empirically, it extends the literature to investigate trends in an immature national system of innovation in a late developing economy context, South Africa. The analysis maps the heterogeneity of academic engagement, focusing on firms, through principal component analysis of an original dataset derived from a survey of individual academics. It concludes that the incentives that drive academics and that block university–industry interaction in contexts like South Africa, are strongly related to universities’ differentiated nature as reputationally controlled work organisations, and to the ways in which they balance and prioritise their roles in national development.

IntroductionSeeing and treating patients in daily practice forms the basis of general practitioner (GP) training. However, the types of patients seen by GP trainees do not always match trainees’ educational needs. Knowledge about factors that shape the mix of patient types is limited, especially with regard to the role of the professionals who work in the GP practice.AimWe investigated factors affecting the mix of patients seen by GP trainees from the perspective of professionals.Design and settingThis qualitative study involved GP trainees, GP supervisors, medical receptionists and nurse practitioners affiliated with a GP Specialty Training Institute in the Netherlands.MethodsTwelve focus groups and seven interviews with 73 participants were held. Data collection and analysis were iterative, using thematic analysis with a constant comparison methodology.ResultsThe characteristics of patients’ health problems and the bond between the doctor and patient are important determinants of GP trainees’ patient mix. Because trainees have not yet developed bonds with patients, they are less likely to see patients with complex health problems. However, trainees can deliberately influence their patient mix by paying purposeful attention to bonding with patients and by gaining professional trust through focused engagement with their colleagues.ConclusionTrainees’ patient mix is affected by various factors. Trainees and team members can take steps to ensure that this mix matches trainees’ educational needs, but their success depends on the interaction between trainees’ behaviour, the attitudes of team members and the context. The findings show how the mix of patients seen by trainees can be influenced to become more trainee centred and learning oriented.

Aim Cardiovascular disease development is highly variable between patients with familial hypercholesterolemia (FH). Since current risk prediction methods fail to estimate the risk of individual patients, all patients are treated with high-intensity lipid-lowering medication like statins and PCSK9-inhibitors. To prevent overtreatment (with its associated costs and side effects) of patients with a low risk, reliable biomarkers are urgently needed. While studying atherosclerosis development in an FH porcine model, we discovered a specific LDL profile that was directly associated with the severity of atherosclerosis development. Methods 10 adult pigs with an LDLR mutation received a high-fat diet for 12 months. Atherosclerosis development in the three main coronary arteries was monitored with intravascular ultrasound (IVUS) and optical coherence tomography at three time points. After sacrifice, tissue was harvested for detailed histological analysis of the coronary plaque composition. Size-exclusion chromatography (SEC, n=10) and LC-MSMS (n=4) were used to assess the plasma lipoprotein profile, and the sphingolipid content of LDL, relative to cholesterol. Results Imaging and histology revealed a marked difference in pigs that developed large, lumen intruding plaques (IVUS-based plaque burden 13–77%) within 9 months (n=5) and pigs (n=5) that only developed early lesions (IVUS-based plaque burden 8–34%), even after 12 months of follow-up. The plaques seen in the fast responding pigs possessed distinct characteristics of advanced disease (i.e. heavy macrophage infiltration, large lipid-rich necrotic cores, neovascularisation, micro- and macrocalcifications and intraplaque haemorrhage, see figure). In these fast responders, fibrous cap atheroma occupied 34% of the total artery. SEC revealed two distinct LDL subclasses: regular and “larger” LDL particles. Fast responding pigs with advanced atherosclerosis displayed a significantly higher ratio in cholesterol concentration of regular/'larger' LDL than slow responding pigs (1.7 (1.3–1.9) vs. 0.8 (0.6–1.2); (p=0.004), see figure). Compared to regular LDL, “larger” LDL contained relatively more sphingolipids in the fast responding than in the slow responding animals (regular LDL/'larger' LDL: S1P 0.5 (0.5–0.5) vs. 1.0 (0.8–1.2); Cer16:0 0.70 (0.67–0.73) vs. 1.04 (0.95–1.13); Cer18:0 0.60 (0.58–0.61) vs. 1.15 (1.13–1.16); Cer20:0 0.73 (0.73–0.74) vs. 0.94 (0.94–0.94)). “Larger” LDL particles and comparable sphingolipid ratios were also observed in FH patients. Cardiovascular data from our FH patient cohort, coupled to the LDL subclass distribution, will provide more insight into the potential of this novel biomarker. Conclusion A distinct difference in LDL subclasses, including a new “larger” LDL particle, was found in fast versus slow responding FH animals. This finding can potentially be used to identify FH patients at the highest risk of CVD to avoid overtreatement of low risk patients. Acknowledgement/Funding ERC- starter grant (grant agreement 310457)

The changes in the cardiovascular function (CVF) during preeclampsia are known. Whether they begin prior clinical manifestation or persist after delivery remains unclear. Objective We hypothesized that preeclampsia is preceded by early CVF changes. We evaluated the eventual difference between patients who develop preeclampsia and those who stayed normotensives. Secondly we searched for a link between CVF changes and development of preeclampsia. Methods This prospective study, included 260 normotensive primiparous women, referred for routinely control to the Cardiology section. At week 22 of gestation and 1 year after delivery were performed: Office blood pressure (OBP), blood and urine lab test. Cardiac index (CI) and systemic vascular resistance index (SVRI) through impedance cardiography. Wave pulse velocity (PWV) through pressure signals. According to the evolution during pregnancy patients were assigned to one of 3 groups: G1 preeclampsia:. G2 Gestational hypertension G3 Normotensive. Statistic tests: one-way analysis of variance and the Bonferroni post-hoc test. Results 12 patients evolved to preeclamsia, 18 to gestational hypertension and 230 remained normotensive. G1 had significantly lower value of CI in both measurements and higher values of OBP, SVRPI and WPV comparing to G3. G2 always showed intermediate values between G1 and G2. The median age of the population was 25 ≠ 4 years old. By logistic regression analysis WPV and SVRI at 22 week of gestation were predictors of preeclampsia. (p Patient Characteristics Characteristics G1 G2 G3 p Conclusion Preeclampsia showed different CVF compare with normotensive, before diagnosis and after delivery. The early endothelial dysfunction could be responsible of these changes.

Carriers of pathogenic variants in CDKN2A have a 70% life-time risk of developing melanoma and 15-20% risk of developing pancreatic cancer (PC). In the Netherlands, a 19-bp deletion in exon 2 of CDKN2A (p16-Leiden mutation) accounts for most hereditary melanoma cases. Clinical experience suggests variability in occurrence of melanoma and PC in p16-Leiden families. Thereby, the risk of developing cancer could be modified by both environmental and genetic contributors, suggesting that identification of genetic modifiers could improve patients’ surveillance. In a recent genome-wide association study (GWAS), rs36115365-C was found to significantly modify risk of PC and melanoma in the European population. This SNP is located on chr5p15.33 and has allele-specific regulatory activities on TERT expression. Herein, we investigated the modifying capacities of rs36115365-C on PC and melanoma in a cohort of 283 p16-Leiden carriers including 29 diagnosed with PC, 171 diagnosed with melanoma, 21 diagnosed with both PC and melanoma and 62 with neither PC nor melanoma. In contrast to previously reported findings, we did not find a significant association of PC risk with risk variant presence as determined by Generalized Estimating Equations (GEE) modelling. Interestingly, carrier-ship of the risk variant had a significant protective effect for melanoma (OR -0.703 [95% CI -1.201-0.205], p = 0.006); however, the observed association was no longer significant after exclusion of probands to assess possible influence of ascertainment. Collectively, genetic modifiers for the prediction of PC and melanoma risk in p16-Leiden carriers remain to be determined.

Objective This study examined the feasibility of a parallel-group assessor-blinded randomized controlled trial investigating whether task-specific training preceded by aerobic exercise (AEX + TST) improves upper limb function more than task-specific training (TST) alone. Methods People with upper limb motor dysfunction after stroke were allocated to TST or AEX + TST. Both groups were prescribed 60 hr of TST over 10 weeks (3 × 1-hr sessions with a therapist per week and 3 × 1 hr of home-based self-practice per week). The AEX + TST group performed 30 minutes of aerobic exercise immediately prior to the 1 hr of TST with the therapist. Recruitment, adherence, retention, participant acceptability, and adverse events were recorded. Clinical measures were performed prerandomization at baseline, on completion of the intervention, and at 1- and 6-month follow-up. Results Fifty-nine persons after stroke were screened, 42 met the eligibility criteria, and 20 (11 male; mean [SD] age: 55.4 [16.0] years; time since stroke: 71.7 [91.2] months) were recruited over 17 months. The mean Wolf Motor Function Test Functional Ability Score at baseline was 27.4 (max = 75) and the mean Action Research Arm Test score was 11.2 (max = 57). Nine were randomized to AEX + TST and 11 to TST. There were no adverse events, but there was one drop out. Retention at 1- and 6-month follow-up was 80% and 85%, respectively. Attendance was 93% (6) for the AEX + TST group, and 89% (9) for the TST group. AEX + TST was perceived as acceptable (100%) and beneficial (87.5%). Exertional fatigue (visual analogue scale) prior to TST was worse in the AEX + TST group (3.5 [0.7] out of 10) than the TST group (1.7 [1.4] out of 10). The TST group performed 31% more repetitions per session than the AEX + TST group. Conclusion A subsequent Phase III study is feasible, but modifications to eligibility criteria, outcome measures, and intervention delivery are recommended.

ObjectivesAdopting an attributional perspective, the current article investigates how audit and feedback group sessions contribute to general practitioners’ (GPs) motivation to change their practice behaviour to improve care. We focus on the contributions of the audit and feedback itself (content) and the group discussion (process).MethodsFour focus groups, comprising a total of 39 participating Dutch GPs, discussed and compared audit and feedback of their practices. The focus groups were analysed thematically.ResultsAudit and feedback contributed to GPs’ motivation to change in two ways: by raising awareness about aspects of their current care practice and by providing indications of the possible impact of change. For these contributions to play out, the audit and feedback should be reliable and valid, specific, recent and recurrent and concern GPs’ own practices or practices within their own influence sphere. Care behaviour attributed to external, uncontrollable or unstable causes would not induce change. The added value of the group is twofold as well: group discussion contributed to GPs’ motivation to change by providing a frame of reference and by affording insights that participants would not have been able to achieve on their own.ConclusionsIn audit and feedback group sessions, both audit and feedback information and group discussion can valuably contribute to GPs’ motivation to change care practice behaviour. Peer interaction can positively contribute to explore alternative practices and avenues for improvement. Local or regional peer meetings would be beneficial in facilitating reflection and discussion. An important avenue for future studies is to explore the contribution of audit and feedback and small-group discussion to actual practice change.

Background:The interferon (IFN) pathway is a complex system with multiple proteins and diverse downstream effects on gene and protein expression. IFNs have been implicated in multiple RMDs. Despite significant potential, IFN assays have not progressed into clinical practice.Objectives:To perform a SLR on IFN assays in RMDs and propose a consensus terminology.Methods:OvidMedline, Embase and Web of Science were searched for reports of IFN and RMDs up to October 2019. Information about the properties of assays measuring type I IFN and measures of truth were extracted and summarised. Terminology was agreed through an interactive consensus process with reference to the existing evidence.Results:10037 abstracts were identified. 275 fulfilled eligibility criteria, and were used for data extraction. Some used more than one technique to measure IFN-I pathway activation. Hence, 275 papers generated data on 393 methods. There was great heterogeneity in the methods used and presentation of results. IFN-I pathway activation was measured using: qPCR (n=121), immunoassays (n=101), microarray (n=69), reporter cell assay (n=38), DNA methylation (n=14), flow cytometry (n=14), cytopathic effect assay (n=11), RNA sequencing (n=9), Plaque reduction assay (n=8), Nanostring (n=5), bisulphite sequencing (n=3). All papers fulfilled Face Validity. Due to lack of gold standard for IFN-I pathway activation, evidence of criterion validity was variable. Concurrent validity was presented for n=150 assays. The terminology used to describe aspects of type I IFN pathway activation was not consistent, so a consensus terminology for IFN research (Table 1) was proposed by the taskforce.Table 1.Consensus terminologyTermAbbreviationDefinitionInterferonIFNProteins with anti-viral activity; IFNs are mediators of an anti-viral response. They belong to the Type I, Type II and Type III IFN families.Type I interferonIFN-IThe IFNs alpha, beta, omega, kappa, epsilon, secreted by any nucleated cell, and binding to the IFNAR, which is expressed on any nucleated cell.Type II interferonIFN-IIIFN gamma, mostly secreted by T cells, binding to the IFNGR, which is expressed on most leucocytes.Type III interferonIFN-IIIIFN lambda, which are structurally more similar to IL-10 but share downstream signalling and gene expression with IFN-I.Interferon-stimulated genesISGsGenes whose expression is known to be upregulated by any kind of IFN. Individual ISGs may not exclusively represent Type I IFN pathway activation.Type I Interferon pathway activationAny evidence for function of the components of the Type I IFN pathway. This includes: secretion of a Type I IFN protein, binding to the IFNAR, initiation of JAK/STAT signalling pathways, expression of IFN-stimulated genes, expression of IFN-stimulated proteins.Type I interferon pathway assayAn assay measuring one or more components of the Type I IFN pathway at a molecular or functional level.Interferon stimulated gene expression signatureA qualitative description of coordinated expression of a set of ISGs that is indicative of Type I IFN pathway activation.Interferon stimulated gene expression scoreA quantitative variable derived from expression of a defined set of ISGs that is indicative of Type I IFN pathway activation.Interferon stimulated protein scoreA variable derived from expression of a defined set of soluble biomarkers known to be upregulated by IFN, although not specific for Type I IFN.InterferonopathyMonogenic diseases in which there is constitutive Type I IFN pathway activation with a causal role in pathology. The clinical picture may resemble rheumatic musculoskeletal diseases. However, most diseases with IFN pathway activation are not Interferonopathies.Conclusion:Diverse methods have been reported as IFN assays and these differ in what elements of type IFN-I pathway activation they measure. The taskforce consensus terminology on type I IFN reporting should be considered for research and clinical applications.Disclosure of Interests:Agata Burska: None declared, Javier Rodriguez Carrio: None declared, Philip G Conaghan: None declared, Willem A Dik: None declared, Robert Biesen: None declared, Maija-leena Eloranta: None declared, Giulio Cavalli: None declared, Marianne Visser: None declared, Dimitrios Boumpas: None declared, George Bertsias: None declared, Marie Wahren-Herlenius: None declared, Jan Rehwinkel: None declared, Marie-Louise Frémond: None declared, Mary K. Crow Consultant of: AstraZeneca, Bristol Meyers Squibb, Lilly, Shannon Pharmaceuticals, Grant/research support from: Gilead, Lars Ronnblom Consultant of: AstraZeneca, Edward Vital Speakers bureau: GSK, Consultant of: AURINIA, SANDOZ, GSK, AstraZeneca, Roche, Modus, Grant/research support from: AstraZeneca, Marjan Versnel: None declared

International audience; Anticipated climatic changes combined with eutrophication are predicted to enhance the dominance of several notorious cyanobacterial taxa. Cyanobacteria have many key ecological traits that may allow them to thrive under foreseen scenarios of environmental change. Understanding the ecophysiological traits of harmful species has proven important for their successful control and management. Indeed, if the links between key cyanobacterial traits and the specific environmental conditions that allow expression of these traits can be disrupted, we could identify (novel) means for operational control and mitigate or prevent water quality problems. A good example is artificial mixing of a lake that breaks down the water column stability on which fast floating, buoyant cyanobacteria depend. Based upon Reynolds’ functional phytoplankton classification, we focused on five groups of cyanobacteria that from a management point of view can be seen as homogeneous and have comparable environmental sensitivities. For each group, we present (1) its key traits, (2) how these characteristics will maintain their function under future environmental change, (3) explanation of how understanding the function of these traits can reveal the “Achilles heel” of the particular functional group and (4) which (combination of) control measures is most likely to be successful. Despite looking for specific environmental sensitivities of individual groups, we maintain that controlling nutrients remains the basis for managing blooms, no matter which functional type dominates. Providing further ecological knowledge to lake management could be the key to effective bloom control and healthier, sustainable freshwater ecosystems even in a warmer future.

Objective Estetrol (E4) is a natural fetal estrogen. The safety of increasing doses of E4 and its preliminary effects on the vagina, endometrium and menopausal vasomotor symptoms were investigated. Study design This was a partly randomized, open-label, multiple-rising-dose study in 49 postmenopausal women. Subjects with an intact uterus were randomized to receive either 2 mg E4 or 2 mg estradiol-valerate (E2V) for 28 days. Subsequent dose-escalation groups (non-randomized) were: 10 mg E4 (intact uterus and ≥35 hot flushes/week); and 20 mg and 40 mg E4 (hysterectomized subjects). Main outcome measure Adverse events (AEs) and vaginal cytology were evaluated in all treatment groups; hot flushes/sweating and endometrial proliferation were analyzed with 2 and 10 mg E4 and 2 mg E2V. Results Estetrol appeared to be safe, without serious drug-related AEs. In all the groups there was a clear shift from parabasal to superficial vaginal cells, indicating an estrogenic effect and a potential for the treatment of vulvovaginal atrophy. The endometrial thickness remained stable in the 2 mg E4 group and increased with E2V and 10 mg E4. A decrease in the mean number of hot flushes and sweating was seen with 2 and 10 mg E4 and 2 mg E2V. Conclusions Estetrol in a dose range of 2–40 mg per day improved vaginal cytology and vasomotor symptoms in postmenopausal women. Endometrial proliferation occurred with the 10 mg dose. Estetrol seems a safe and suitable candidate to develop further for hormone therapy.

To help ban the use of general toxic algicides, research efforts are now directed towards the discovery of compounds that are specifically acting as cyanocides. Here, we review the past and look forward into the future, where the less desirable general algicides like copper sulphate, diuron or endothall may become replaced by compounds that show better specificity for cyanobacteria and are biodegradable or transform into non-toxic products after application. For a range of products, we review the activity, the mode of action, effectiveness, durability, toxicity towards non-target species, plus costs involved, and discuss the experience with and prospects for small water volume interventions up to the mitigation of entire lakes; we arrive at recommendations for a series of natural products and extracted organic compounds or derived synthetic homologues with promising cyanocidal properties, and briefly mention emerging nanoparticle applications. Finally, we detail on the recently introduced application of hydrogen peroxide for the selective killing of cyanobacteria in freshwater lakes.

A high-level audit of administrative databases was conducted in more than 20 national government departments or entities. The aim was to investigate the relevance of datasets within these databases to skills planning by the government aimed at harmonising skills supply and demand in South Africa. The audit revealed that datasets have different levels of relevance and usability. There are datasets that: are relevant and immediately usable; are highly relevant and require some preparation; contain relevant variables but are currently undergoing validation and cleaning before they can be utilised; and are in an early stage of evolution. Based on these observations, the authors furthermore explore how databases can be understood from an evolutionary perspective. This investigation provides evidence that, in the field of skills planning, the government is progressing through the early phases of e-government systems development by cataloguing data resources and preparing for transactions between data us...

In early August 2014, the municipality of Toledo, OH (USA) issued a ‘do not drink’ advisory on their water supply directly affecting over 400,000 residential customers and hundreds of businesses (Wilson, 2014). This order was attributable to levels of microcystin, a potent liver toxin, which rose to 2.5 μg L−1 in finished drinking water. The Toledo crisis afforded an opportunity to bring together scientists from around the world to share ideas regarding factors that contribute to bloom formation and toxigenicity, bloom and toxin detection as well as prevention and remediation of bloom events. These discussions took place at an NSF- and NOAA-sponsored workshop at Bowling Green State University on April 13 and 14, 2015. In all, more than 100 attendees from six countries and 15 US states gathered together to share their perspectives. The purpose of this review is to present the consensus summary of these issues that emerged from discussions at the Workshop. As additional reports in this special issue provide detailed reviews on many major CHAB species, this paper focuses on the general themes common to all blooms, such as bloom detection, modeling, nutrient loading, and strategies to reduce nutrients.

Blended learning (the combination of electronic methods with traditional teaching methods) has the potential to combine the best of traditional education with the best of computer-mediated training. We chose to develop such an intervention for GP trainers who were undertaking a Continuing Medical Education (CME) course in evidence-based medicine (EBM). This study reports on our experience and investigated the factors influencing the perception on usefulness and logistics of blended learning for learners in CME. In total, 170 GP trainers participated in the intervention. We used questionnaires, observations during the four face-to-face meetings and evaluations in the e-course over one year. Additionally we organised focus groups to gain insight in some of the outcomes of the questionnaires and interpretations of the observations. The GP trainers found the design and the educational method (e-course in combination with meetings) attractive, instructive and complementary. Factors influencing their learning were (1) educational design, (2) educational method, (3) topic of the intervention, (4) time (planning), (5) time (intervention), (6) learning style, (7) technical issues, (8) preconditions and (9) level of difficulty. A close link between daily practice and the educational intervention was considered an important precondition for the success of the intervention in this group of learners. GP trainers were positive about blended learning: they found e-learning a useful way to gain knowledge and the meetings a pleasant way of transferring the knowledge into practice. Although some preconditions should be taken into consideration during its development and implementation, they would participate in similarly designed learning in the future

Background and Purpose— This study investigated whether problem-solving therapy (PST) is an effective group intervention for improving coping strategy and health-related quality of life (HRQoL) in patients with stroke. Methods— In this multicenter randomized controlled trial, the intervention group received PST as add-on to standard outpatient rehabilitation, the control group received outpatient rehabilitation only. Measurements were performed at baseline, directly after the intervention, and 6 and 12 months later. Data were analyzed using linear-mixed models. Primary outcomes were task-oriented coping as measured by the Coping Inventory for Stressful Situations and psychosocial HRQoL as measured by the Stroke-Specific Quality of Life Scale. Secondary outcomes were the EuroQol EQ-5D-5L utility score, emotion-oriented and avoidant coping as measured by the Coping Inventory for Stressful Situations, problem-solving skills as measured by the Social Problem Solving Inventory-Revised, and depression as measured by the Center for Epidemiological Studies Depression Scale. Results— Included were 166 patients with stroke, mean age 53.06 years (SD, 10.19), 53% men, median time poststroke 7.29 months (interquartile range, 4.90–10.61 months). Six months post intervention, the PST group showed significant improvement when compared with the control group in task-oriented coping ( P =0.008), but not stroke-specific psychosocial HRQoL. Furthermore, avoidant coping ( P =0.039) and the utility value for general HRQoL ( P =0.034) improved more in the PST group than in the control after 6 months. Conclusions— PST seems to improve task-oriented coping but not disease-specific psychosocial HRQoL after stroke >6-month follow-up. Furthermore, we found indications that PST may improve generic HRQoL recovery and avoidant coping. Clinical Trial Registration— URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2509 . Unique identifier: CNTR2509.

Background: Nutrition studies in the intensive care unit (ICU) have shown that adequate enteral nutrition (EN) support has clinical benefits. However, the course of amino acid concentrations in plasma has never been investigated in patients admitted with shock receiving EN. We hypothesized that plasma concentrations, when deficit, increase during EN and that persistent deficiency is associated with poor outcome. Methods: In 33 septic or cardiogenic shock patients receiving EN, plasma amino acid concentrations were measured during 5 days. Changes in amino acid concentrations, correlations with clinical outcome variables, and regression analyses were studied. Results: On ICU admission, several plasma concentrations were deficient. Plasma concentrations of almost all amino acids increased. In contrast, taurine decreased by >50%, from 47.6 μmol/L on admission to 20.0 μmol/L at day 1, and remained low at day 5. Taurine (admission) correlated with time on mechanical ventilation (R = -0.42, P =.015). Taurine decrease within 24 hours correlated with Acute Physiology and Chronic Health Evaluation II predicted mortality (R = 0.43, P =.017) and Sequential Organ Failure Assessment score (R = 0.36, P =.05). Regression analyses confirmed correlations. Conclusions: Several amino acids were deficient in plasma on ICU admission but increased during EN. Taurine concentrations declined and were associated with longer periods of mechanical ventilation and ICU support. Fast taurine decline correlated with severity of organ failure. These findings support the role of taurine during ischemia, reperfusion, and inflammation. Taurine may be an essential candidate to enrich nutrition support for critically ill patients, although more research is required.

A quality system (named GEAR; acronym for Combined Evaluation Audit Round in English), has been introduced in eight institutes of the Dutch general practitioner specialty training. This paper focuses on the local and national effects of GEAR. Seventeen semi-structured interviews were conducted with the directors and quality co-ordinators. At a local level, GEAR provided the institutes with insights into their current practice. The institutes designed and implemented several improvement plans based on feedback. Furthermore, GEAR addressed quality management more systematically, and it enhanced the quality culture. At a national level, the institutes formulated national priorities. In addition, GEAR stimulated collaboration as a result of more frequent contacts. Institutes differed in their perception of the extent to which GEAR offered added value. Integrating the quality system into the local policy was sometimes a problem. Despite some scepticism at the start, GEAR provoked enthusiasm that can contribute to the quality of medical education.

Under ongoing climate change and increasing anthropogenic activity, which continuously challenge ecosystem resilience, an in-depth understanding of ecological processes is urgently needed. Lakes, as providers of numerous ecosystem services, face multiple stressors that threaten their functioning. Harmful cyanobacterial blooms are a persistent problem resulting from nutrient pollution and climate-change induced stressors, like poor transparency, increased water temperature and enhanced stratification. Consistency in data collection and analysis methods is necessary to achieve fully comparable datasets and for statistical validity, avoiding issues linked to disparate data sources. The European Multi Lake Survey (EMLS) in summer 2015 was an initiative among scientists from 27 countries to collect and analyse lake physical, chemical and biological variables in a fully standardized manner. This database includes in-situ lake variables along with nutrient, pigment and cyanotoxin data of 369 lakes in Europe, which were centrally analysed in dedicated laboratories. Publishing the EMLS methods and dataset might inspire similar initiatives to study across large geographic areas that will contribute to better understanding lake responses in a changing environment., The authors acknowledge COST Action ES 1105 “CYANOCOST – Cyanobacterial blooms and toxins in water resources: Occurrence impacts and management” and COST Action ES 1201 “NETLAKE – Networking Lake Observatories in Europe” for contributing to this study through networking and knowledge sharing with European experts in the field. Evanthia Mantzouki was supported by a grant from the Swiss State Secretariat for Education, Research and Innovation (SERI) to Bas Ibelings and by supplementary funding from University of Geneva. We thank Wendy Beekman for the nutrient analysis and the University of Wageningen for covering the costs of this analysis from the personal funding of dr. Miquel Lürling. We thank Pieter Slot for assisting with the pigment analysis and the University of Amsterdam for covering the costs of the analysis through funding from the group of Prof. Jef Huisman and dr. Petra Visser (IBED). We would like to thank the Environmental Data Initiative for covering the cost of archiving the EMLS dataset. We would like to thank the Leibniz Institute of Freshwater Ecology and Inland Fisheries, Dept. of Experimental Limnology and the Aquatic Microbial Ecology Group for logistic and technical support of J. Fonvielle and H.-P. Grossart; and the Leibniz Association for financial support. The collection of data for Lough Erne and Lough Neagh were funded by the Department of Agriculture, Environment and Rural Affairs, Northern Ireland.

In the effort to achieve the Sustainable Development Goals (SDGs) related to food, health, water, and climate, an increase in pressure on land is highly likely. To avoid further land degradation and promote land restoration, multifunctional use of land is needed within the boundaries of the soil-water system. In addition, awareness-raising, a change in stakeholders&rsquo, attitudes, and a change in economics are essential. The attainment of a balance between the economy, society, and the biosphere calls for a holistic approach. In this paper, we introduce four concepts that we consider to be conducive to realizing LDN in a more integrated way: systems thinking, connectivity, nature-based solutions, and regenerative economics. We illustrate the application of these concepts through three examples in agricultural settings. Systems thinking lies at the base of the three others, stressing feedback loops but also delayed responses. Their simultaneous use will result in more robust solutions, which are sustainable from an environmental, societal, and economic point of view. Solutions also need to take into account the level of scale (global, national, regional, local), stakeholders&rsquo, interests and culture, and the availability and boundaries of financial and natural capital. Furthermore, sustainable solutions need to embed short-term management in long-term landscape planning. In conclusion, paradigm shifts are needed. First, it is necessary to move from excessive exploitation in combination with environmental protection, to sustainable use and management of the soil-water system. To accomplish this, new business models in robust economic systems are needed based on environmental systems thinking, an approach that integrates environmental, social, and economic interests. Second, it is necessary to shift from a &ldquo, system follows function&rdquo, approach towards a &ldquo, function follows system&rdquo, one. Only by making the transition towards integrated solutions based on a socio-economical-ecological systems analysis, using concepts such as nature-based solutions, do we stand a chance to achieve Land Degradation Neutrality by 2030. To make these paradigm shifts, awareness-raising in relation to a different type of governance, economy and landscape and land-use planning and management is needed.

This paper compares four LPV identification methods: local, global, and glocal, for flutter prediction and modeling. Important properties of the methods are highlighted and simulations are performed to compare the performance, using a bending-torsion flutter model from literature. Results show that a trade-off between bias and variance exists for the local and global method, after which a glocal method can further improve performance.

We have developed a computer model of plant community dynamics for Louisiana’s coastal wetland ecosystems. The model was improved as a part of the Louisiana Coastal Master Plan of 2017 and is one of several linked models used to evaluate the potential effects of climate change and sea levels rise as well as the potential effects of alternative approaches to managing the region’s natural resources to mitigate the effects of sea level rise. The model we describe here incorporates a number of improvements over the previous version of the model developed for the 2012 Master Plan, including an expansion of the number of species and habitat types represented, the inclusion of bottomland forests and barrier islands, and the incorporation of additional ecological processes such as dispersal. Here, we present results from the model used to evaluate large scale ecosystem restoration projects, as well as three alternative management scenarios to illustrate the utility of the model and the ability of current management plans to address the threats that sea level rise pose to Louisiana’s coastal wetland ecosystems.

There is a growing body of evidence that links nutrition to muscle mass, strength and function in older adults, suggesting that it has an important role to play both in the prevention and management of sarcopenia. This review summarises the discussions of a working group [ESCEO working group meeting 8th September 2016] that met to review current evidence and to consider its implications for preventive and treatment strategies. The review points to the importance of 'healthier' dietary patterns that are adequate in quality in older age, to ensure sufficient intakes of protein, vitamin D, antioxidant nutrients and long-chain polyunsaturated fatty acids. In particular, there is substantial evidence to support the roles of dietary protein and physical activity as key anabolic stimuli for muscle protein synthesis. However, much of the evidence is observational and from high-income countries. Further high-quality trials, particularly from more diverse populations, are needed to enable an understanding of dose and duration effects of individual nutrients on function, to elucidate mechanistic links, and to define optimal profiles and patterns of nutrient intake for older adults. (C) 2017 The Authors. Published by Elsevier Ltd.

An experiment was designed using optimal design of experiments to identify the most relevant parameters in an assembly step for a smart tag; the soldering of 0402 resistors to a polyimide backplane. The parameter window was set to reflect natural variations in production, and parameter variations were investigated to ascertain whether these variations could lead to unacceptable values of electrical resistance or shear-strength of the soldered joints. All tests were performed before and after exposure to hygrothermal aging, i.e. exposure to 85 °C in combination with 85 % RH, and/or cyclic bending. All test results gave values well within the predefined failure criteria. It could therefore be concluded that all of the tested combinations of parameters spanning the tested process window can be considered as safe variations for the assembly of 0402 resistors in the production of the smart tags. The parameters that influenced the electrical resistance and shear-strength of these assemblies were identified.

Background: Case studies are core constructs used in information management research. A persistent challenge for business, information management and social science researchers is how to select a representative sample of cases among a population with diverse characteristics when convenient or purposive sampling is not considered rigorous enough. The context of the study is post-school education, and it involves an investigation of quantitative methods of clustering the population of public technical and vocational education and training (TVET) colleges in South Africa into groups with a similar level of maturity in terms of their information systems. Objectives: The aim of the study was to propose an evidence-based quantitative method for the selection of cases for case study research and to demonstrate the use and usefulness thereof by clustering public TVET colleges. Method: The clustering method was based on the use of a representative characteristic of the context, as a proxy. In this context of management information systems (MISs), website maturity was used as a proxy and website maturity model theory was used in the development of an evaluation questionnaire. The questionnaire was used for capturing data on website characteristics, which was used to determine website maturity. The websites of the 50 public TVET colleges were evaluated by nine evaluators. Multiple statistical techniques were applied to establish inter-rater reliability and to produce clusters of colleges. Results: The analyses revealed three clusters of public TVET colleges based on their website maturity levels. The first cluster includes three colleges with no websites or websites at a low maturity level. The second cluster consists of 30 colleges with websites at an average maturity level. The third cluster contains 17 colleges with websites at a high maturity level. Conclusion: The main contribution to the knowledge domain is an innovative quantitative method employing a characteristic (in this case website maturity) as a proxy for MIS maturity. The method can be applied in quantitative, qualitative and mixed methods research, to group a population and thereby simplify the process of sample selection of cases for further in-depth investigation.

Estetrol (E4) is a natural fetal estrogen. In this open-label, multiple-rising-dose study, the pharmacokinetic effects of E4 in postmenopausal women were investigated as a secondary objective.In total, 49 postmenopausal women were randomized to receive either 2 mg E4 or 2 mg estradiol valerate (E2V) for 28 days, or were (non-randomized) assigned to 10, 20, or 40 mg E4. The main outcome measures were: E4 plasma concentrations at trough, and on days 1 and 28; and E4 pharmacokinetic parameters AUC, CAfter oral administration, E4 showed a very fast absorption, followed by a multiphasic elimination with an initial rapid decline, gradually continuing with a slower elimination, suggesting a long terminal half-life. Steady state was reached within 2 weeks of dosing and pharmacokinetic results were generally proportional to the dose. Estetrol concentrations on day 28 were slightly higher compared to day 1, indicating some accumulation.The pharmacokinetic profile of estetrol is characterized by a very fast absorption phase, followed by an initial rapid decline, and a slow terminal elimination phase. Based on its kinetic properties, estetrol seems suitable for use as a once-daily oral drug.

A novel bending machine has been designed and tested. It enables flexible electronics to be subjected to repeated bending with constant radius and tension. In-situ electrical characterization can give accurate analysis of lifetime distributions if sufficiently many samples are ran to failure, allowing reliability prediction models to be developed. Four sets of test samples with different combinations of substrate, routing, interconnect technology and components were examined. A poor level of reliability was observed when using anisotropic conductive paste to form interconnects, whereas a significantly higher level of reliability was observed when using a bismuth-tin solder paste. The assembly of larger components resulted in shortened time to failure, whereas increasing the bending radius prolonged the observed lifetimes.

International audience; This review aims to summarise the outcomes of some recent European research concerning toxic cyanobacteria and cyanotoxins, with an emphasis on developments within the framework of the CYANOCOST Action (COST Action ES1105, Cyanobacterial Blooms and Toxins in Water Resources: Occurrence, Impacts and Management). State of the art research and management capabilities in Europe on cyanobacteria have benefitted from input from the pure and applied life sciences, the human and animal health sectors, water engineers, economists and planners. Many of these professional groups have been brought together and they interacted favourably within the framework of CYANOCOST. Highlights of the Action include phycological and ecological studies, development of advanced techniques for cyanotoxin analysis, elucidation of cyanotoxin modes of action, management techniques to reduce cyanobacterial mass development, and research on methods and practices for cyanotoxin removal during drinking water treatment. The CYANOCOST Action has had an active outreach policy throughout its lifetime, resulting in e.g. three handbooks, two special issues in scientific journals and activities in the social media. The many contact channels to end-users, including environmental and drinking water supply authorities, health professionals and the general public are described in this review. Furthermore, the authors have identified a number of gaps in knowledge. Proposed directions for future research in the field of toxic cyanobacteria and cyanotoxins are also discussed