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The wflow_sbm hydrological model, recently released by Deltares, as part of the Wflow.jl (v0.7.3) modelling framework, is being used to better understand and potentially address multiple operational and water resource planning challenges from a catchment scale to national scale to continental and global scale. Wflow.jl is a free and open-source distributed hydrological modelling framework written in the Julia programming language. The development of wflow_sbm, the model structure, equations and functionalities are described in detail, including example applications of wflow_sbm. The wflow_sbm model aims to strike a balance between low-resolution, low-complexity and high-resolution, high-complexity hydrological models. Most wflow_sbm parameters are based on physical characteristics or processes, and at the same time wflow_sbm has a runtime performance well suited for large-scale high-resolution model applications. Wflow_sbm models can be set a priori for any catchment with the Python tool HydroMT-Wflow based on globally available datasets and through the use of point-scale (pedo)transfer functions and suitable upscaling rules and generally result in a satisfactory (0.4 ≥ Kling–Gupta efficiency (KGE) < 0.7) to good (KGE ≥ 0.7) performance for discharge a priori (without further tuning). Wflow_sbm includes relevant hydrological processes such as glacier and snow processes, evapotranspiration processes, unsaturated zone dynamics, (shallow) groundwater, and surface flow routing including lakes and reservoirs. Further planned developments include improvements on the computational efficiency and flexibility of the routing scheme, implementation of a water demand and allocation module for water resource modelling, the addition of a deep groundwater concept, and computational efficiency improvements through for example distributed computing and graphics processing unit (GPU) acceleration.

Abstract Surface electroenterography is a potential non-invasive alternative to current diagnostics of colonic motility disorders. However, electrode positioning in electroenterography is often based on general anatomy and may lack generalizability. Furthermore, the repeatability of electroenterography measurements is unknown. This study aimed to evaluate ultrasound-guided electrode positioning for electroenterography measurements and to determine the repeatability of those measurements. In ten healthy adults, two electroenterography procedures were performed, consisting of fasting, ultrasound-guided electrode localization and two 20-minute electroenterography recordings separated by a meal. The dominant frequency, the mean power density (magnitude of colonic motility) and the power percent difference (relative pre- to postprandial increase in magnitude) were determined. Repeatability was determined by Lin’s concordance correlation coefficient. The results demonstrated that the dominant frequency did not differ between pre- and postprandial recordings and was 3 cpm, characteristic of colonic motility. The mean power density increased between the pre- and postprandial measurements, with an average difference of over 200%. The repeatability of both the dominant frequency and power density was poor to moderate, whereas the correlation coefficient of the power percent difference was poor. Concluding, ultrasound-guided surface electroenterography seems able to measure the gastrocolic reflex, but the dissatisfactory repeatability necessitates optimization of the measurement protocol.

Abstract Background Although being a woman and having a migration background are strong predictors of poor self-rated health among (older) adults, research on the sex difference in self-rated health among (older) migrants remains limited. This study therefore aims to investigate this topic and explore the contributing role of determinants of self-rated health. Methods Cross-sectional data from 360 Turkish-Dutch and Moroccan-Dutch adults aged 55–65 as part of the Longitudinal Aging Study Amsterdam (LASA) were used. Self-rated health (good versus poor) was measured by a single item question. Univariate age-adjusted logistic regression analysis was used to investigate the sex difference in self-rated health and the contribution of sex differences in sensitivity (strength of the association) and/or exposure (prevalence) to socio-demographic, social, lifestyle or health-related determinants of self-rated health. Results Women had a 0.53 times lower odds (95%CI:0.40–0.82, p = 0.004) on good self-rated health compared to men. Women more often having a lower education level, living alone and having a higher prevalence of depressive symptoms, chronic diseases and especially functional limitations contributed to the lower self-rated health among women. In contrast, men were more sensitive to the impact of memory complaints, depressive symptoms, visual difficulties and functional limitations. Conclusions Older Turkish-Dutch and Moroccan-Dutch women have a significant lower self-rated health compared to men. Women having a higher exposure to both socio-demographic and health-related determinants of self-rated health, which contributed to the sex difference. Future research should take these differences in self-rated health and determinants between women and men into account when investigating health among older migrants.

Abstract Background The goal is to estimate the additional value of ultrasonographic optic nerve sheath diameter (ONSD) measurement on days 1–3, on top of electroencephalography (EEG), pupillary light reflexes (PLR), and somatosensory evoked potentials (SSEP), for neurological outcome prediction of comatose cardiac arrest patients. We performed a prospective longitudinal cohort study in adult comatose patients after cardiac arrest. ONSD was measured on days 1–3 using ultrasound. Continuous EEG, PLR, and SSEP were acquired as standard care. Poor outcome was defined as cerebral performance categories 3–5 at 3–6 months. Logistic regression models were created for outcome prediction based on the established predictors with and without ONSD. Additional predictive value was assessed by increase in sensitivity for poor (at 100% specificity) and good outcome (at 90% specificity). Results We included 100 patients, 54 with poor outcome. Mean ONSD did not differ significantly between patients with good and poor outcome. Sensitivity for predicting poor outcome increased by adding ONSD to EEG and SSEP from 25% to 41% in all patients and from 27% to 50% after exclusion of patients with non-neurological death. Conclusions ONSD on days 1–3 after cardiac arrest holds potential to add to neurological outcome prediction. Trial registration: clinicaltrials.gov, NCT04084054. Registered 10 September 2019, https://www.clinicaltrials.gov/study/NCT04084054 .

Ongezonde leefstijl en lichamelijke achteruitgang : samenvatting Het doel van deze studie was de samenhang te onderzoeken tussen ongezonde leefstijl op jonge, middelbare, en/of oudere leeftijd en lichamelijke achteruitgang op oudere leeftijd en tussen chronische blootsteling aan een ongezonde leefstijl in de loop van het leven, en lichamelijke achteruitgang op oudere leeftijd. De steekproef bestond uit 1297 respondenten van de Longitudinal Aging Study Amsterdam (LASA). Leefstijl op oudere leeftijd (55-85 jaar) werd gemeten op baseline en op jonge (circa 25 jaar) en middelbare (circa 40 jaar) leeftijd retrospectief nagevraagd en bestond uit lichamelijke activiteit, body mass index (BMI), het aantal alcoholische consumpties per week en roken. Lichamelijke achteruitgang werd berekend als het verschil in de score op lichamelijke prestatietesten tussen baseline en 6-jaar followup. Op oudere leeftijd was een BMI tussen 25-29 versus BMI

Abstract Background Women have a higher life expectancy than men but experience more years with physical disabilities in daily life at older ages, especially women with a migration background. This pinpoints older women as an important target group for strategies that stimulate healthy lifestyle, which benefits healthy aging. Our study investigates motivators and barriers for healthy lifestyles and perspectives on determinants of healthy aging of older women. This provides essential information for developing targeted strategies. Methods Data was collected by semi-structured digital interviews from February till June 2021. Women aged 55 years and older living in the Netherlands (n = 34) with a native Dutch (n = 24), Turkish (n = 6) or Moroccan (n = 4) migration background were included. Two main subjects were investigated: (1) motivators and barriers on their current lifestyles regarding smoking, alcohol consumption, physical activity, diet and sleep and (2) perspectives on determinants of healthy aging. Interviews were analyzed using Krueger’s framework. Results Personal health was the most common motivator for a healthy lifestyle. In addition, peer pressure and being outdoors were specific motivators for physical activity. Bad weather conditions and personal dislike to be active were specific barriers. The social environment, personal preferences and personal belief to compensate with other healthy lifestyle behaviors were barriers for low alcohol consumption. Personal preferences (liking unhealthy food and not making time) were the main barriers for a healthy diet. Sleep was not perceived as a form of lifestyle behavior, but rather as a personal trait. Since there were no smokers, specific barriers were not mentioned. For Turkish-Dutch and Moroccan-Dutch women, additional barriers and motivators were culture and religion. These were strong motivators to abstain from alcohol consumption and smoking, but a barrier for a healthy diet. With regard to perspectives on determinants of healthy aging, positive views on aging and being physically active were perceived as most important. Women often wanted to increase their physical activity or healthy diet to stimulate healthy aging. Among Turkish-Dutch and Moroccan-Dutch women, healthy aging was also perceived as something in the hands of God. Conclusions Although motivators and barriers for a healthy lifestyle and perspectives on healthy aging vary for distinct lifestyles, personal health is a common motivator across all lifestyles. Having a migration background added culture and religion as distinct barriers and motivations. Strategies to improve lifestyle among older women should therefore have a tailored, culture sensitive approach (if applicable) for distinct lifestyle factors.

This study presents the first azimuth cutoff analysis in Synthetic Aperture Radar (SAR) altimetry, aiming to assess its applicability in characterizing sea-state dynamics. In SAR imaging, the azimuth cutoff serves as a proxy for the shortest waves, in terms of wavelength, that can be detected by the satellite under certain wind and wave conditions. The magnitude of this parameter is closely related to the wave orbital velocity variance, a key parameter for characterizing wind-wave systems. We exploit wave modulations exhibited in the tail of fully-focused SAR waveforms and extract the azimuth cutoff from the radar signal through the analysis of its along-track autocorrelation function. We showcase the capability of Sentinel-6A in deriving these two parameters based on analyses in the spatial and wavenumber domains, accompanied by a discussion of the limitations. We use Level-1A high-resolution Sentinel-6A data from one repeat cycle (10 days) globally to verify our findings against wave modeled data. In the spatial domain analysis, the estimation of azimuth cutoff involves fitting a Gaussian function to the along-track autocorrelation function. Results reveal pronounced dependencies on wind speed and significant wave height, factors primarily determining the magnitude of the velocity variance. In extreme sea states, the parameters are underestimated by the altimeter, while in relatively calm sea states and in the presence of swells, a substantial overestimation trend is observed. We introduce an alternative approach to extract the azimuth cutoff by identifying the fall-off wavenumber in the wavenumber domain. Results indicate effective mitigation of swell-induced errors, with some additional sensitivity to extreme sea states compared to the spatial domain approach.

In dit artikel wordt verslag gedaan van resultaten uit de Longitudinal Aging Study Amsterdam (LASA). LASA is een onderzoek naar determinanten en gevolgen van veranderingen in dagelijks functioneren. Voor dit artikel is verandering in het lichamelijk functioneren als centraal thema gekozen. Uit de longitudinale resultaten komt naar voren dat veel ouderen functieverlies ervaren, vooral naarmate hun leeftijd toeneemt. Een veelheid van factoren, zoals chronische ziekten, cognitieve achteruitgang, depressie, sociaal economische status en leefstijl, hangt samen met functieverlies. Voor een deel zijn dit oorzakelijke factoren, voor een ander deel zijn het kenmerken van groepen met verhoogde kans op achteruitgang. Uit trendanalyses blijkt dat de prevalentie van lichamelijke beperkingen geen vast gegeven is, maar in de tijd verandert. Het LASA-onderzoek geeft aanwijzingen dat deze prevalentie toeneemt bij ouderen vanaf 55 jaar. In het licht van de absolute en relatieve toename van het aantal ouderen in de bevolking is het dan ook van groot belang om te zorgen dat achteruitgang in lichamelijk functioneren minder vaak voorkomt en naar latere leeftijd wordt verschoven. Op grond van de resultaten worden hiertoe enkele suggesties gedaan. Tevens worden richtingen voor vervolgonderzoek aangegeven.

Abstract Pharmacologically disrupting fear memory reconsolidation dramatically reduces fear behaviour. For example, 2–3 min of tarantula exposure followed by 40 mg of propranolol HCl (i.e., a reconsolidation intervention) abruptly decreased spider avoidance, an effect that persisted one year later. However, the success of reconsolidation interventions is not guaranteed: Pavlovian fear-conditioning research shows that the window to target memory reconsolidation is small and easy to miss. If exposure is too long to trigger reconsolidation, but too short for extinction learning, an inactive transitional limbo state occurs, rendering the fear memory unchanged and insensitive to amnesic agents. In this pre-registered study, we aimed to find this behaviourally-controlled boundary condition. Spider-fearful participants underwent a ~3 min (n = 23) or ~14 min (n = 20) exposure to a tarantula, intended to trigger reconsolidation or the limbo state respectively, followed by 40 mg of propranolol. We expected greater spider fear reduction after 3 than 14 min of exposure. Unexpectedly, there were no group differences on any outcome measures. In both groups, Bayesian analysis revealed a marked reduction in fear behaviour towards a generalisation stimulus (a house spider) accompanied by lower self-reported distress, with a sharp decline in spider fear scores two days after treatment that persisted one year later. Possible explanations include that the boundary conditions of reconsolidation are wider in older and stronger memories than experimentally-induced fears, or that alternative processes caused the treatment effects. Although the mechanism is unclear, these results carry a tentative promising message for the potential of brief reconsolidation-targeting interventions to mitigate irrational fears.

Abstract Background Individuals with type 2 diabetes mellitus (T2DM) have an increased risk for developing macrovascular disease (MVD) manifested by atherosclerosis. Phenotypically and functionally different monocyte subsets (classical; CD14++CD16−, non-classical; CD14+CD16++, and intermediate; CD14++CD16+) including pro-angiogenic monocytes expressing Tie2 (TEMs) can be identified. Here we investigated monocyte heterogeneity and its association with T2DM and MVD. Methods Individuals with (N = 51) and without (N = 56) T2DM were recruited and allocated to "non-MVD" or "with MVD" (i.e., peripheral or coronary artery disease) subgroups. Blood monocyte subsets were quantified based on CD14, CD16 and Tie2 expression levels. Plasma levels of Tie2-ligands angiopoietin-1 and angiopoietin-2 were determined using ELISA. Carotid endarterectomy samples from individuals with (N = 24) and without (N = 22) T2DM were stained for intraplaque CD68+ macrophages (inflammation) and CD34+ (angiogenesis), as plaque vulnerability markers. Results Monocyte counts were similar between individuals with T2DM and healthy controls (non-diabetic, non-MVD). Non-classical monocytes were reduced (p

BackgroundEthnicity impacts cardiovascular disease (CVD) risk, and South Asians demonstrate a higher risk than White Europeans. Arterial stiffness is known to contribute to CVD, and differences in arterial stiffness between ethnicities could explain the disparity in CVD risk. We compared central and local arterial stiffness between White Europeans and South Asians and investigated which factors are associated with arterial stiffness.MethodsData were collected from cohorts of White Europeans (the Netherlands) and South Asians (India). We matched cohorts on individual level using age, sex, and body mass index (BMI). Arterial stiffness was measured with ARTSENS® Plus. Central stiffness was expressed as carotid-femoral pulse wave velocity (cf-PWV, m/s), and local carotid stiffness was quantified using the carotid stiffness index (Beta) and pressure-strain elastic modulus (Epsilon, kPa). We compared arterial stiffness between cohorts and used multivariable linear regression to identify factors related to stiffness.ResultsWe included n = 121 participants per cohort (age 53±10 years, 55% male, BMI 24 kg/m2). Cf-PWV was lower in White Europeans compared to South Asians (6.8±1.9 vs. 8.2±1.8 m/s, p0.05 for interaction). Systolic blood pressure was associated with carotid stiffness in both cohorts, whereas age was associated to carotid stiffness only in South Asians and BMI only in White Europeans.ConclusionEthnicity is associated with central but not local arterial stiffness. Conversely, ethnicity seems to modify associations between CVD risk factors and local but not central arterial stiffness. This suggests that ethnicity interacts with arterial stiffness measures and the association of these measures with CVD risk factors.

Objectives There is a broad call for change towards ‘new era’ quality systems in healthcare, in which the focus lies on learning and improving. A promising way to establish this in general practice care is to combine audit and feedback with peer group discussion. However, it is not known what different stakeholders think of this type of quality improvement. The aim of this research was to explore the opinions of different stakeholders in general practice on peer discussion of audit and feedback and on its opportunities and risks. Second, their thoughts on transparency versus accountability, regarding this system, were studied.Design An exploratory qualitative study within a constructivist paradigm. Semistructured interviews and focus group discussions were held and coded using thematic analysis. Included stakeholders were general practitioners (GP), patients, professional organisations and insurance companies.Setting General practice in the Netherlands.Participants 22 participants were purposively sampled for eight interviews and two focus group discussions.Results Three main opportunities of peer discussion of audit and feedback were identified: deeper levels of reflection on data, adding context to numbers and more ownership; and three main risks: handling of unwilling colleagues, lacking a safe group and the necessity of patient involvement. An additional theme concerned disagreement on the amount of transparency to be offered: insurance companies and patients advocated for complete transparency on data and improvement of outcomes, while GPs and professional organisations urged to restrict transparency to giving insight into the process.Conclusions Peer discussion of audit and feedback could be part of a change movement, towards a quality system based on learning and trust, that is initiated by the profession. Creating a safe learning environment and involving patients is key herein. Caution is needed when complete transparency is asked, since it could jeopardise practitioners’ reflection and learning in safety.

Aesthetic aspects of drinking water, such as Taste and Odor (T&O), have significant effects on consumer perceptions and acceptability. Solving unpleasant water T&O episodes in water supplies is challenging, since it requires expertise and know-how in diagnosis, evaluation of impacts and implementation of control measures. We present gaps, challenges and perspectives to advance water T&O science and technology, by identifying key areas in sensory and chemical analysis, risk assessment and water treatment, as articulated by WaterTOP (COST Action CA18225), an interdisciplinary European and international network of researchers, experts, and stakeholders.

Abstract Background Infectious blood meal experiments have been frequently performed with different virus-vector combinations to assess the transmission potential of arthropod-borne (arbo)viruses. A wide variety of host blood sources have been used to deliver arboviruses to their arthropod vectors in laboratory studies. The type of blood used during vector competence experiments does not always reflect the blood from the viremic vertebrate hosts in the field, but little is known about the effect of blood source on the experimental outcome of vector competence studies. Here we investigated the effect of avian versus human blood on the infection and transmission rates of the zoonotic Usutu virus (USUV) in its primary mosquito vector Culex pipiens. Methods Cx. pipiens biotypes (pipiens and molestus) were orally infected with USUV through infectious blood meals containing either chicken or human whole blood. The USUV infection and transmission rates were determined by checking mosquito bodies and saliva for USUV presence after 14 days of incubation at 28 °C. In addition, viral titers were determined for USUV-positive mosquito bodies and saliva. Results Human and chicken blood lead to similar USUV transmission rates for Cx. pipiens biotype pipiens (18% and 15%, respectively), while human blood moderately but not significantly increased the transmission rate (30%) compared to chicken blood (17%) for biotype molestus. USUV infection rates with human blood were consistently higher in both Cx. pipiens biotypes compared to chicken blood. In virus-positive mosquitoes, USUV body and saliva titers did not differ between mosquitoes taking either human or chicken blood. Importantly, biotype molestus had much lower USUV saliva titers compared to biotype pipiens, regardless of which blood was offered. Conclusions Infection of mosquitoes with human blood led to higher USUV infection rates as compared to chicken blood. However, the blood source had no effect on the vector competence for USUV. Interestingly, biotype molestus is less likely to transmit USUV compared to biotype pipiens due to very low virus titers in the saliva.

Abstract Benthic cyanobacterial mats (BCMs) are becoming increasingly common on coral reefs. In Fiji, blooms generally occur in nearshore areas during warm months but some are starting to prevail through cold months. Many fundamental knowledge gaps about BCM proliferation remain, including their composition and how they influence reef processes. This study examined a seasonal BCM bloom occurring in a 17-year-old no-take inshore reef area in Fiji. Surveys quantified the coverage of various BCM-types and estimated the biomass of key herbivorous fish functional groups. Using remote video observations, we compared fish herbivory (bite rates) on substrate covered primarily by BCMs (> 50%) to substrate lacking BCMs (

Abstract Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus that is pathogenic to ruminants and humans. The virus is endemic to Africa and the Arabian Peninsula where outbreaks are characterized by abortion storms and mortality of newborns, particularly in sheep herds. Vector competence experiments in laboratory settings have suggested that over 50 mosquito species are capable of transmitting RVFV. Transmission of mosquito-borne viruses in the field is however influenced by numerous factors, including population densities, blood feeding behavior, extrinsic incubation period, longevity of vectors, and viremia levels in vertebrate hosts. Animal models to study these important aspects of RVFV transmission are currently lacking. In the present work, RVFV was transmitted to European (Texel-swifter cross-breed) lambs by laboratory-reared Aedes aegypti mosquitoes that were infected either by membrane feeding on a virus-spiked blood meal or by feeding on lambs that developed viremia after intravenous inoculation of RVFV. Feeding of mosquitoes on viremic lambs resulted in strikingly higher infection rates as compared to membrane feeding. Subsequent transmission of RVFV from lamb to lamb by infected mosquitoes was highly efficient in both models. The animal models described here can be used to study mosquito-mediated transmission of RVFV among the major natural target species and to evaluate the efficacy of vaccines against mosquito-mediated RVFV infection.

Abstract Background Emerging arboviral diseases like Zika, dengue and chikungunya that are transmitted by Aedes aegypti mosquitoes, are increasingly threatening human health. Blends of human-like synthetic chemical attractants can be used to attract host-seeking mosquitoes. The aim of this study was to test new combinations of traps and odour baits in the laboratory, followed by testing the best candidates in the field to improve Ae. aegypti monitoring and surveillance. Methods First, the BG-Suna trap was evaluated for capturing laboratory-reared Ae. aegypti by testing normal and inverted positions in screen cage tests. Secondly, the attractiveness of the MB5 blend, CO2, and their combination was tested. Thirdly, we tested the attractiveness of different trap types (BG-Suna, BG-Sentinel, MM-X and CDC light trap). Finally, we confirmed laboratory results in the field in Paramaribo, Suriname, using the MB5 and BG-Lure odour blends, CO2 and the BG-Sentinel and BG-Bowl trap using a Latin Square design. Results The MB5 blend in combination with CO2 outperformed traps baited only with CO2 or MB5 in screen cage tests (P

Past research has shown that attributions of intentions to other's actions determine how we experience these actions and their consequences. Yet, it is unknown how such attributions affect our learning and memory. Addressing this question, we combined neuroimaging with an interactive threat learning paradigm in which two interaction partners (confederates) made choices that had either threatening (shock) or safe (no shock) consequences for the participants. Importantly, participants were led to believe that one partner intentionally caused the delivery of shock, whereas the other did not (i.e. unintentional partner). Following intentional versus unintentional shocks, participants reported an inflated number of shocks and a greater increase in anger and vengeance. We applied a model-based representational similarity analysis to blood-oxygen-level-dependent (BOLD)-MRI patterns during learning. Surprisingly, we did not find any effects of intentionality. The threat value of actions, however, was represented as a trial-by-trial increase in representational similarity in the insula and the inferior frontal gyrus. Our findings illustrate how neural pattern formation can be used to study a complex interaction.

Over the last decades, Roman wood in various shapes and sizes has been excavated in the region of the continental north-western provinces of the Roman empire. However, it is often unclear whether wood has been transported. Most dendrochronological provenance studies rely on simple comparisons between tree-ring series based on a single similarity measure. In addition, most fail to consider the complex system of relations that is the result of the variables that influence tree-ring patterns. Network analysis is a solution to this problem, because it allows to both visualize and analyze the complex (provenance) relations of tree-ring series as a whole. A network makes it impossible to ignore existing (statistical) relations between tree-ring series. Although networks can be build using any (combination of) similarity measure(s), in this study a combination of the Synchronous Growth Changes (SGC), its related probability of exceedance ('p'), correlation ('r') and overlap define the edges. This paper focusses on networks with site chronologies as nodes, although networks can also be constructed using individual tree-ring series or a combination with site chronologies. A combination of these can also help to refine the (archaeological) interpretation. The location of any tree-ring series in a network reflects its provenance. Material that is placed closer together in the network has similar growth patterns and is generally from the same region. Therefore, network communities reflect wood that has a similar provenance. If tree-ring material was found on different spatial locations, but in close proximity in the network, this indicates that wood has been moved. To determine which wood has been transported, a combination of archaeological and spatial arguments is used. The method is sound, simple and gives insight in the complexity of all tree-ring relations in a simple diagram. The resulting patterns show that most wood was obtained in the region where it was used, but that transport of wood in the Roman period did take place. Three scales are defined to describe the Roman wood economy: local, provincial and imperial. While transport of wood over long distances is attested for both military and civilian sites (provincial and imperial scale), it seems that wood that was transported beyond the provincial borders was only used in civilian sites (imperial scale). The combination of network science, dendrochronology and archaeology is a powerful method to understand patterns in the Roman timber economy.

ABSTRACTUsutu virus (USUV) and West Nile virus (WNV) are closely related mosquito-borne flaviviruses that are mainly transmitted between bird hosts by vector mosquitoes. Infections in humans are incidental but can cause severe disease. USUV is endemic in large parts of Europe, while WNV mainly circulates in Southern Europe. In recent years, WNV is also frequently detected in Northern Europe, thereby expanding the area where both viruses co-circulate. However, it remains unclear how USUV may affect the future spread of WNV and the likelihood of human co-infection. Here we investigated whether co-infections with both viruses in cell lines and their primary mosquito vector, Culex pipiens, affect virus replication and transmission dynamics. We show that USUV is outcompeted by WNV in mammalian, avian and mosquito cells during co-infection. Mosquitoes that were exposed to both viruses simultaneously via infectious blood meal displayed significantly reduced USUV transmission compared to mosquitoes that were only exposed to USUV (from 15% to 3%), while the infection and transmission of WNV was unaffected. In contrast, when mosquitoes were pre-infected with USUV via infectious blood meal, WNV transmission was significantly reduced (from 44% to 17%). Injection experiments established the involvement of the midgut in the observed USUV-mediated WNV inhibition. The competition between USUV and WNV during co-infection clearly indicates that the chance of concurrent USUV and WNV transmission via a single mosquito bite is low. The competitive relation between USUV and WNV may impact virus transmission dynamics in the field and affect the epidemiology of WNV in Europe.

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.

Most vertebrate RNA viruses show pervasive suppression of CpG and UpA dinucleotides, closely resembling the dinucleotide composition of host cell transcriptomes. In contrast, CpG suppression is absent in both invertebrate mRNA and RNA viruses that exclusively infect arthropods. Arthropod-borne (arbo) viruses are transmitted between vertebrate hosts by invertebrate vectors and thus encounter potentially conflicting evolutionary pressures in the different cytoplasmic environments. Using a newly developed Zika virus (ZIKV) model, we have investigated how demands for CpG suppression in vertebrate cells can be reconciled with potentially quite different compositional requirements in invertebrates and how this affects ZIKV replication and transmission. Mutant viruses with synonymously elevated CpG or UpA dinucleotide frequencies showed attenuated replication in vertebrate cell lines, which was rescued by knockout of the zinc-finger antiviral protein (ZAP). Conversely, in mosquito cells, ZIKV mutants with elevated CpG dinucleotide frequencies showed substantially enhanced replication compared to wild type. Host-driven effects on virus replication attenuation and enhancement were even more apparent in mouse and mosquito models. Infections with CpG- or UpA-high ZIKV mutants in mice did not cause typical ZIKV-induced tissue damage and completely protected mice during subsequent challenge with wild-type virus, which demonstrates their potential as live-attenuated vaccines. In contrast, the CpG-high mutants displayed enhanced replication in Aedes aegypti mosquitoes and a larger proportion of mosquitoes carried infectious virus in their saliva. These findings show that mosquito cells are also capable of discriminating RNA based on dinucleotide composition. However, the evolutionary pressure on the CpG dinucleotides of viral genomes in arthropod vectors directly opposes the pressure present in vertebrate host cells, which provides evidence that an adaptive compromise is required for arbovirus transmission. This suggests that the genome composition of arbo flaviviruses is crucial to maintain the balance between high-level replication in the vertebrate host and persistent replication in the mosquito vector.

BACKGROUND:Bayesian networks (BNs) are machine-learning-based computational models that visualize causal relationships and provide insight into the processes underlying disease progression, closely resembling clinical decision-making. Preoperative identification of patients at risk for lymph node metastasis (LNM) is challenging in endometrial cancer, and although several biomarkers are related to LNM, none of them are incorporated in clinical practice. The aim of this study was to develop and externally validate a preoperative BN to predict LNM and outcome in endometrial cancer patients. METHODS AND FINDINGS:Within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC), we performed a retrospective multicenter cohort study including 763 patients, median age 65 years (interquartile range [IQR] 58-71), surgically treated for endometrial cancer between February 1995 and August 2013 at one of the 10 participating European hospitals. A BN was developed using score-based machine learning in addition to expert knowledge. Our main outcome measures were LNM and 5-year disease-specific survival (DSS). Preoperative clinical, histopathological, and molecular biomarkers were included in the network. External validation was performed using 2 prospective study cohorts: the Molecular Markers in Treatment in Endometrial Cancer (MoMaTEC) study cohort, including 446 Norwegian patients, median age 64 years (IQR 59-74), treated between May 2001 and 2010; and the PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study cohort, including 384 Dutch patients, median age 66 years (IQR 60-73), treated between September 2011 and December 2013. A BN called ENDORISK (preoperative risk stratification in endometrial cancer) was developed including the following predictors: preoperative tumor grade; immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), p53, and L1 cell adhesion molecule (L1CAM); cancer antigen 125 serum level; thrombocyte count; imaging results on lymphadenopathy; and cervical cytology. In the MoMaTEC cohort, the area under the curve (AUC) was 0.82 (95% confidence interval [CI] 0.76-0.88) for LNM and 0.82 (95% CI 0.77-0.87) for 5-year DSS. In the PIPENDO cohort, the AUC for 5-year DSS was 0.84 (95% CI 0.78-0.90). The network was well-calibrated. In the MoMaTEC cohort, 249 patients (55.8%) were classified with

Abstract Background More than 60% of women diagnosed with early stage breast cancer receive (neo)adjuvant chemotherapy. Breast cancer patients receiving chemotherapy often experience symptoms such as nausea, vomiting and loss of appetite that potentially affect body weight and body composition. Changes in body weight and body composition may detrimentally affect their quality of life, and could potentially increase the risk of disease recurrence, cardiovascular disease and diabetes. To date, from existing single method (quantitative or qualitative) studies is not clear whether changes in body weight and body composition in breast cancer patients are treatment related because previous studies have not included a control group of women without breast cancer. Methods We therefore developed the COBRA-study (Change Of Body composition in BReast cancer: All-in Assessment-study) to assess changes in body weight, body composition and related lifestyle factors such as changes in physical activity, dietary intake and other behaviours. Important and unique features of the COBRA-study is that it used I) a “Mixed Methods Design”, in order to quantitatively assess changes in body weight, body composition and lifestyle factors and, to qualitatively assess how perceptions of women may have influenced these measured changes pre-, during and post-chemotherapy, and II) a control group of non-cancer women for comparison. Descriptive statistics on individual quantitative data were combined with results from a thematic analysis on the interviews- and focus group data to understand patients’ experiences before, during and after chemotherapy. Discussion The findings of our mixed methods study, on chemotherapy treated cancer patients and a comparison group, can enable healthcare researchers and professionals to develop tailored intervention schemes to help breast cancer patients prevent or handle the physical and mental changes they experience as a result of their chemotherapy. This will ultimately improve their quality of life and could potentially reduce their risk for other co-morbidity health issues such as cardiovascular disease and diabetes.

BACKGROUND:The Asian bush mosquito Aedes japonicus is invading Europe and was first discovered in Lelystad, the Netherlands in 2013, where it has established a permanent population. In this study, we investigated the vector competence of Ae. japonicus from the Netherlands for the emerging Zika virus (ZIKV) and zoonotic Usutu virus (USUV). ZIKV causes severe congenital microcephaly and Guillain-Barré syndrome in humans. USUV is closely related to West Nile virus, has recently spread throughout Europe and is causing mass mortality of birds. USUV infection in humans can result in clinical manifestations ranging from mild disease to severe neurological impairments. METHODOLOGY/PRINCIPAL FINDINGS:In our study, field-collected Ae. japonicus females received an infectious blood meal with ZIKV or USUV by droplet feeding. After 14 days at 28°C, 3% of the ZIKV-blood fed mosquitoes and 13% of the USUV-blood fed mosquitoes showed virus-positive saliva, indicating that Ae. japonicus can transmit both viruses. To investigate the effect of the mosquito midgut barrier on virus transmission, female mosquitoes were intrathoracically injected with ZIKV or USUV. Of the injected mosquitoes, 96% (ZIKV) and 88% (USUV) showed virus-positive saliva after 14 days at 28°C. This indicates that ZIKV and USUV can efficiently replicate in Ae. japonicus but that a strong midgut barrier is normally restricting virus dissemination. Small RNA deep sequencing of orally infected mosquitoes confirmed active replication of ZIKV and USUV, as demonstrated by potent small interfering RNA responses against both viruses. Additionally, de novo small RNA assembly revealed the presence of a novel narnavirus in Ae. japonicus. CONCLUSIONS/SIGNIFICANCE:Given that Ae. japonicus can experimentally transmit arthropod-borne viruses (arboviruses) like ZIKV and USUV and is currently expanding its territories, we should consider this mosquito as a potential vector for arboviral diseases in Europe.

Abstract Background The Motivational Interviewing target Scheme (MITS) is an instrument to assess competency in Motivational Interviewing (MI) and can be used to assess MI in long and brief consultations. In this qualitative study we examined two sources of the Unified Model of Validity, the current standard of assessment validation, in the context of General Practice. We collected evidence concerning response process validity and content validity of the MITS in general practice. Furthermore, we investigated its feasibility. Methods Assessing consultations of General Practitioners and GP-trainees (GPs), the assessors systematically noted down their considerations concerning the scoring process and the content of the MITS in a semi-structured questionnaire. Sampling of the GPs was based on maximum variation and data saturation was used as a stopping criterion. An inductive approach was used to analyse the data. In response to scoring problems the score options were adjusted and all consultations were assessed using the original and the adjusted score options. Results Twenty seven assessments were needed to reach data saturation. In most consultations, the health behaviour was not the reason for encounter but was discussed on top of discussing physical problems. The topic that was most discussed in the consultations was smoking cigarettes. The adjusted score options increased the response process validity; they were more in agreement with theoretical constructs and the observed quality of MI in the consultations. Concerning content validity, we found that the MITS represents the broad spectrum and the current understanding of MI. Furthermore, the MITS proved to be feasible to assess MI in brief consultations in general practice. Conclusions Based on the collected evidence the MITS seems a promising instrument to measure MI interviewing in brief consultations. The evidence gathered in this study lays the foundation for research into other aspects of validation.

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

Abstract Background Weight gain during chemotherapy in women with breast cancer is commonly reported. However, there are important differences between studies that examined weight change during chemotherapy; e.g. type of chemotherapy, menopausal status, time between body weight measurements and sample size. The purpose of this meta-analysis was to quantify changes in body weight during chemotherapy for women with breast cancer, taking these differences into account. Methods We identified relevant studies using PubMed, Scopus and Embase databases. The search was limited to human studies published in English up to and including December 2015. Only studies among women with early stage breast cancer treated with chemotherapy, with reported body weight before and after chemotherapy and type of chemotherapy were included. Random-effect models were used, and heterogeneity between studies was explored through stratified analyses and meta-regression. Sensitivity analyses were done to explore whether a specific study markedly affected the results. Results In total 25 papers were found, including data from 2620 women. Overall, body weight increased during chemotherapy: 2.7 kg (95% CI 2.0, 7.5) with a high degree of heterogeneity (I2 = 94.2%). Stratified analyses showed weight gain in all strata, but did not substantially reduce heterogeneity. Univariate meta-regression showed less weight gain in prospective studies compared to chart review studies (−2.0, 95% CI: -3.1, −0.8). Studies including cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimes showed a greater weight gain compared to those that did not (2.2, 95% CI: 1.1, 3.3); and papers published until the year 2000 showed a greater weight gain compared to those published after 2000 (1.9, 95% CI:-0.8, 3.1). In the multivariate models only studies including CMF regimes and studies published until 2000 were associated with significant weight gain of respectively 1.3 and 1.4 kg. Conclusion Despite the high heterogeneity, this meta-analysis shows significant weight gain during chemotherapy for women with breast cancer. Weight gain was more pronounced in papers published until 2000 and women receiving CMF as chemotherapy regime. Although weight gain after chemotherapy has decreased over the course of time, weight gain is still substantial and deserves clinical attention.

Introduction Seeing 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.Aim We investigated factors affecting the mix of patients seen by GP trainees from the perspective of professionals.Design and setting This qualitative study involved GP trainees, GP supervisors, medical receptionists and nurse practitioners affiliated with a GP Specialty Training Institute in the Netherlands.Methods Twelve focus groups and seven interviews with 73 participants were held. Data collection and analysis were iterative, using thematic analysis with a constant comparison methodology.Results The 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.Conclusion Trainees’ 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.

Background: The acquired skill set prior to school entry has emerged as an important issue in research and policy internationally. Much evidence exists advocating the importance of early numeracy and literacy skills in later academic achievement and economic outcomes of students. Aim: The goal of this study was to determine the association between parents’ reports of engagement in pre-Grade 1 learning activities and school entry skills, and mathematics achievement in Grade 5. Setting: This study was based on empirical evidence using South African data from the 2015 Trends in International Mathematics and Science Study. Methods: These relationships were investigated by using stepwise multiple regression analysis. Results: It was found that parent reports of engagement in pre-Grade 1 activities and acquired school entry skills are positively associated with student achievement at the Grade 5 level. This held even when taking other contextual home factors into account: socio-economic status and the frequency of speaking the language of the test at home. Conclusion: The role of the home is important in preparing children for school and has an impact on their later achievement. The home context should therefore be a key consideration in enhancing the South African education system. Parent reports are a good indicator of engagement in early learning activities and acquired numeracy and literacy skills prior to school entry.

Applying low concentrations of hydrogen peroxide (H2O2) to lakes is an emerging method to mitigate harmful cyanobacterial blooms. While cyanobacteria are very sensitive to H2O2, little is known about the impacts of these H2O2 treatments on other members of the microbial community. In this study, we investigated changes in microbial community composition during two lake treatments with low H2O2 concentrations (target: 2.5 mg L−1) and in two series of controlled lake incubations. The results show that the H2O2 treatments effectively suppressed the dominant cyanobacteria Aphanizomenon klebahnii, Dolichospermum sp. and, to a lesser extent, Planktothrix agardhii. Microbial community analysis revealed that several Proteobacteria (e.g., Alteromonadales, Pseudomonadales, Rhodobacterales) profited from the treatments, whereas some bacterial taxa declined (e.g., Verrucomicrobia). In particular, the taxa known to be resistant to oxidative stress (e.g., Rheinheimera) strongly increased in relative abundance during the first 24 h after H2O2 addition, but subsequently declined again. Alpha and beta diversity showed a temporary decline but recovered within a few days, demonstrating resilience of the microbial community. The predicted functionality of the microbial community revealed a temporary increase of anti-ROS defenses and glycoside hydrolases but otherwise remained stable throughout the treatments. We conclude that the use of low concentrations of H2O2 to suppress cyanobacterial blooms provides a short-term pulse disturbance but is not detrimental to lake microbial communities and their ecosystem functioning.

Abstract Background Favourable trends in risk factor levels in the general population may partly explain the decline in coronary heart disease (CHD) morbidity and mortality. Our aim was to present long-term national trends in established risk factors for CHD. Methods Data were obtained from five data sources including several large scale population based surveys, cohort studies and general practitioner registers between 1988 and 2012. We applied linear regression models to age-standardized time trends to test for statistical significant trends. Analyses were stratified by sex and age (younger