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Aedes aegypti and A. albopictus mosquitoes are the main vectors for dengue virus (DENV) and other arboviruses, including Zika virus (ZIKV). Understanding the factors that affect transmission of arboviruses from mosquitoes to humans is a priority because it could inform public health and targeted interventions. Reasoning that interactions among viruses in the vector insect might affect transmission, we analysed the viromes of 815 urban Aedes mosquitoes collected from 12 countries worldwide. Two mosquito-specific viruses, Phasi Charoen-like virus (PCLV) and Humaita Tubiacanga virus (HTV), were the most abundant in A. aegypti worldwide. Spatiotemporal analyses of virus circulation in an endemic urban area revealed a 200% increase in chances of having DENV in wild A. aegypti mosquitoes when both HTV and PCLV were present. Using a mouse model in the laboratory, we showed that the presence of HTV and PCLV increased the ability of mosquitoes to transmit DENV and ZIKV to a vertebrate host. By transcriptomic analysis, we found that in DENV-infected mosquitoes, HTV and PCLV block the downregulation of histone H4, which we identify as an important proviral host factor in vivo.

This study combines standard dendrochronological analyses with network science and spatial analysis to determine the provenance of wood used to build river barges in the Roman period. The river barges studied were found in the Lower Rhine region and would have carried bulk goods, such as grain, military supplies, and building materials. The importance of these vessels in the supply of the local economy and military units is evident since many were found in the area, including some in the vicinity of military complexes. However, it remains unknown where these ships were built and how and where the raw materials for their construction were obtained. To better understand the provenance of the wood, network science was applied to visualise and understand the complex patterns of similarity between the tree-ring curves. For the interpretation of the networks we have studied the context, the position of the trees in the network and the use of these trees in shipbuilding. In addition, the shape of the converted timber was used to visualise the wood use patterns in this type of Roman-period shipbuilding. For the river barges, we were able to determine several possible regions for wood procurement. Based on the analysed material, we assume that there was at least one shipyard in the Lower Rhine region where two ships, found in separate excavations, were most likely produced at the same time.

BackgroundWhile neuroimaging has provided insights into the formation of episodic memories in relation to voluntary memory recall, less is known about neural mechanisms that cause memories to occur involuntarily, for example, as intrusive memories of trauma. Here, we investigated brain activity shortly after viewing distressing events as a function of whether memories for those events later intruded involuntarily. The postencoding period is particularly important because it is a period when clinical interventions could be applied.MethodsA total of 32 healthy volunteers underwent functional magnetic resonance imaging while viewing distressing film clips, interspersed with 5 minutes of awake (postencoding) rest. Voluntary memories of the films were assessed using free recall and verbal and visual recognition tests after a week, while intrusive (involuntary) memories were recorded in a diary throughout that week.ResultsWhen analyzing functional magnetic resonance imaging responses related to watching the films, we replicated findings that those “hotspots” (salient moments within the films) that would later become intrusive memories elicited higher activation in parts of the brain’s salience network. Surprisingly, while the postencoding persistence of multivoxel correlation structures associated with entire film clips predicted subsequent voluntary recall, there was no evidence that they predicted subsequent intrusions.ConclusionsResults replicate findings regarding the formation of intrusive memories during encoding and extend findings regarding the consolidation of information in postencoding rest in relation to voluntary memory. While we provided a first step using a naturalistic paradigm, further research is needed to elucidate the role of postencoding neural processes in the development of intrusive memories.

Purpose To conduct a scoping review to provide a systematic overview of outcomes used in nutritional intervention studies focused on the treatment of protein-energy malnutrition in older adults. Methods A systematic search of four electronic databases (Medline, EMBASE, CINAHL and Cochrane Central Register of Controlled Trials (CENTRAL) was performed to retrieve randomized controlled trials (RCTs), published until March 9, 2020, that evaluated the effect of nutritional interventions to treat protein-energy malnutrition in older adults and those at risk for malnutrition. Two authors screened titles, abstracts and full texts independently. One author extracted data that were cross-checked by another author. Results Sixty-three articles reporting 60 RCTs were identified. Most frequently used outcomes included body weight/body mass index (75.0% of RCTs), dietary intake (61.7%), functional limitations (48.3%), handgrip strength (46.7%), and body circumference (40.0%). The frequencies differed by setting (community, hospital and long-term care). For some outcomes there was a preferred assessment method (e.g., Barthel index for functional limitations), while for other outcomes (e.g., functional performance) a much greater variation was observed. Conclusion A large variation in outcomes, not only across but also within settings, was identified in nutritional intervention studies in malnourished older adults and those at risk. Furthermore, for many outcomes there was a large variation in the used assessment method. These results highlight the need for developing a Core Outcome Set for malnutrition intervention studies in older adults to facilitate future meta-analyses that may enhance our understanding on the effectiveness of treatment.

Background: The comparison of recovery patterns for different care pathways following COVID-19 is necessary for optimizing rehabilitation strategies. Objectives: To evaluate cognitive and psychological outcomes across different care pathways up to 12 months after hospitalization for COVID-19. Methods: CO-FLOW is an ongoing multicenter prospective cohort study with assessments at 3, 6, and 12 months after hospitalization for COVID-19. The main outcomes are cognitive deficits (Montreal Cognitive Assessment, score 43), posttraumatic stress disorder (PTSD; Impact of Event Scale-Revised, score ≥33), and anxiety and depression (Hospital Anxiety and Depression Scale, subscale score ≥11). Results: In total, data from 617 participants were analyzed. Mean age was 59.7 (SD 11.4) years and 188 (31%) were female. Significant recovery occurred within the first 6 months post-discharge (p ≤ 0.001). Cognitive deficits persisted in 21% (101/474), and psychological problems in 15% (74/482) of people at 12 months. Significantly improved cognition scores were reported for people who did not receive rehabilitation (‘No-rehab’; 124/617, 20%; mean difference, MD 2.32, 95% CI 1.47 to 3.17; p

Maladaptive emotional memories are a transdiagnostic feature of mental health problems. Therefore, understanding whether and how emotional memories can change might help to prevent and treat mental disorders. We tested whether neutral memories of naturalistic events can retroactively acquire positive or negative affect, in a preregistered three-day Modification of Valence in Episodes (MOVIE) paradigm. On Day 1, participants (N = 41) encoded memories of neutral movie scenes, representing lifelike naturalistic experiences. On Day 2, they retrieved each episode before viewing a happy, sad, or neutral scene from the same movie (resulting in a neutral-negative, neutral-positive, and neutral-neutral condition). On Day 3, participants again retrieved each memory from Day 1. We assessed the affective tone of episodes through facial expressions of positive and negative affect and through self-reported feelings. Positive updating of neutral episodes led to increased expressions of positive affect, whereas negative updating led to increased self-reported negative feelings. These results suggest that complex neutral episodic memories can retroactively acquire an affective tone, but the effects were modest and inconsistent across affect readouts. Future research should investigate alternative approaches to updating emotional memories that produce more profound changes in the valence of memories.

Patients with high-grade endometrial carcinoma (EC) have an increased risk of tumor spread and lymph node metastasis (LNM). Preoperative imaging and CA125 can be used in work-up. As data on cancer antigen 125 (CA125) in high-grade EC are limited, we aimed to study primarily the predictive value of CA125, and secondarily the contributive value of computed tomography (CT) for advanced stage and LNM. Patients with high-grade EC (n = 333) and available preoperative CA125 were included retrospectively. The association of CA125 and CT findings with LNM was analyzed by logistic regression. Elevated CA125 ((>35 U/mL), (35.2% (68/193)) was significantly associated with stage III-IV disease (60.3% (41/68)) compared with normal CA125 (20.8% (26/125), [p < 0.001]), and with reduced disease-specific—(DSS) (p < 0.001) and overall survival (OS) (p < 0.001). The overall accuracy of predicting LNM by CT resulted in an area under the curve (AUC) of 0.623 (p < 0.001) independent of CA125. Stratification by CA125 resulted in an AUC of 0.484 (normal), and 0.660 (elevated). In multivariate analysis elevated CA125, non-endometrioid histology, pathological deep myometrial invasion ≥50%, and cervical involvement were significant predictors of LNM, whereas suspected LNM on CT was not. This shows that elevated CA125 is a relevant independent predictor of advanced stage and outcome specifically in high-grade EC.

Effectiveness of innovative, gamified interventions (i.e., Augmented Reality, Computer-Based Cognitive Retraining [CBCR], and Virtual Reality [VR] in conjunction with a Serious Game) for cognitive training in paediatric ABI was evaluated. Studies were identified on PsycINFO, PubMed and Scopus; last searched 4 January 2022. Eligibility criteria were participants diagnosed with ABI and aged ≤ 18 years, experimental intervention to train cognition, cognition assessed pre- and post-intervention at: (1) The level of function, or (2) The level of activity, and written in English. ROB 2 and ROBINS-I were utilised to assess risk of bias. Extracted study characteristics were methods, participants, interventions, outcomes, and results. Seven studies were included, comprising six CBCR studies and one VR study, with 182 participants. Following CBCR: (1) Improvements were observed in several cognitive functions, but there was inconsistent evidence; (2) Improvements were reported in attention and executive functions (EF) at home and at school. Following VR: (1) Improvements were observed in attention and EF; (2) Not evaluated. Due to the small number of included studies with (relatively) small and heterogeneous samples, only a cautious interpretation of the evidence was provided. There is a need for carefully designed studies with more attention to inter-individual differences and generalisation to daily life. ispartof: Neuropsychological Rehabilitation pages:1-32 ispartof: location:England status: Published online

Background Malnutrition (i.e., protein-energy malnutrition) in older adults is associated with significant complications and increased mortality, highlighting the need for effective treatments. Many randomised controlled trials (RCTs) testing the effectiveness of nutritional interventions for the treatment of malnutrition showed mixed results and there is a need for meta-analyses. However, evidence synthesis is hampered by the wide variety of outcomes and assessment methods in RCTs. This project, led by EuGMS Special Interest Group Nutrition, aims to develop a Core Outcome Set (COS) for nutritional intervention studies in older adults with malnutrition and those at risk. Methods The project consists of five phases: 1) a scoping review (completed) to identify frequently used outcomes in published RCTs and select additional patient-reported outcome measures (PROMs). Patient and Public Involvement (PPI) representatives have been involved to provide feedback on the proposed list of outcomes resulting from the review and PROMs; 2) a modified Delphi Survey whereby experienced researchers and health care professionals working in the field of malnutrition in older adults will be invited to rate the importance of the proposed outcomes; 3) a consensus meeting to discuss and agree what critical outcomes need to be included in the COS; 4) a systematic review to determine how each COS outcome should be measured and a second consensus meeting; 5) a dissemination and implementation phase. Conclusions The result of this project will be a COS that should be included in any RCT testing the effectiveness of interventions to tackle malnutrition in older people as a minimum. This COS will facilitate comparison of RCT results, will promote efficient use of research resources and might reduce bias in measurement of the outcome and publication bias. Ultimately, the COS will support clinical decision making by identifying the most effective approaches for treating and preventing malnutrition in older adults.

Most of our knowledge about human emotional memory comes from animal research. Based on this work, the amygdala is often labeled the brain's “fear center”, but it is unclear to what degree neural circuitries underlying fear and extinction learning are conserved across species. Neuroimaging studies in humans yield conflicting findings, with many studies failing to show amygdala activation in response to learned threat. Such null findings are often treated as resulting from MRI-specific problems related to measuring deep brain structures. Here we test this assumption in a mega-analysis of three studies on fear acquisition (n= 98; 68 female) and extinction learning (n= 79; 53 female). The conditioning procedure involved the presentation of two pictures of faces and two pictures of houses: one of each pair was followed by an electric shock [a conditioned stimulus (CS+)], the other one was never followed by a shock (CS–), and participants were instructed to learn these contingencies. Results revealed widespread responses to the CS+compared with the CS–in the fear network, including anterior insula, midcingulate cortex, thalamus, and bed nucleus of the stria terminalis, but not the amygdala, which actually responded stronger to the CS–. Results were independent of spatial smoothing, and of individual differences in trait anxiety and conditioned pupil responses. In contrast, robust amygdala activation distinguished faces from houses, refuting the idea that a poor signal could account for the absence of effects. Moving forward, we suggest that, apart from imaging larger samples at higher resolution, alternative statistical approaches may be used to identify cross-species similarities in fear and extinction learning.SIGNIFICANCE STATEMENTThe science of emotional memory provides the foundation of numerous theories on psychopathology, including stress and anxiety disorders. This field relies heavily on animal research, which suggests a central role of the amygdala in fear learning and memory. However, this finding is not strongly corroborated by neuroimaging evidence in humans, and null findings are too easily explained away by methodological limitations inherent to imaging deep brain structures. In a large nonclinical sample, we find widespread BOLD activation in response to learned fear, but not in the amygdala. A poor signal could not account for the absence of effects. While these findings do not disprove the involvement of the amygdala in human fear learning, they challenge its typical portrayals and illustrate the complexities of translational science.

Hellweger et al . (Reports, 27 May 2022, pp. 1001) predict that phosphorus limitation will increase concentrations of cyanobacterial toxins in lakes. However, several molecular, physiological, and ecological mechanisms assumed in their models are poorly supported or contradicted by other studies. We conclude that their take-home message that phosphorus load reduction will make Lake Erie more toxic is seriously flawed.

BACKGROUD: The sudden COVID-19 pandemic forced quick development of care pathways for patients with different needs. Trajectories of physical recovery in hospitalized patients for COVID-19 following different care pathways are unknown. We aimed to assess trajectories of physical recovery and levels of physical function reached within the different care pathways. Additionally, we assessed differences in physical function across care pathways at follow-up visits.METHODS: This multicenter prospective cohort study of adults who had been hospitalized for COVID-19 was performed in 10 centers, including 7 hospitals (1 academic and 6 regional hospitals) and 3 rehabilitation centers (1 medical rehabilitation center and 2 skilled nursing facilities), located in the Netherlands. Study visits were performed at 3, 6, and 12 months post-hospital discharge and included assessment of cardiorespiratory fitness (6 min walk test [6MWT], 1 min sit-to-stand test [1MSTST]), muscle strength (maximum handgrip strength [HGS]) and mobility (de Morton Mobility Index [DEMMI]).FINDINGS: We report findings for 582 patients who had been discharged from hospital between March 24, 2020 and June 17, 2021. Patients had a median age of 60·0 years, 68·9% (401/582) were male, 94·6% (561/582) had received oxygen therapy, and 35·2% (205/582) mechanical ventilation. We followed patients across four different rehabilitation settings: no rehabilitation (No-rehab, 19·6% [114/582]), community-based rehabilitation (Com-rehab, 54·1% [315/582]), medical rehabilitation (Med-rehab, 13·7% [80/582]), and rehabilitation in a skilled nursing facility (SNF-rehab, 12·5% [73/582]). Overall, outcomes in 6MWT (14·9 meters [95% CI 7·4 to 22·4]), 1MSTST (2·2 repetitions [1·5 to 2·8]), and HGS (3·5 kg [2·9 to 4·0]) improved significantly (pINTERPRETATION: Overall, physical function improved after hospitalization for COVID-19, with largest improvement within 6 months post-discharge. Patients with rehabilitation after hospital discharge improved in more than one component of physical function, whereas patients without rehabilitation improved solely in muscle strength. Patients who received rehabilitation, and particularly patients with Med- and SNF-rehab, had more severe impairment in physical function at 3 months, but reached equal levels at 12 months compared to patients without follow-up treatment. Our findings indicate the importance of rehabilitation.FUNDING: ZonMw, Rijndam Rehabilitation, Laurens (The Netherlands).

In residential settings for juveniles with Mild Intellectual Disability (MID) employees have to face tough work conditions, because of frequent aggressive incidents Eventually, this might result in a negative work climate, high staff-turnover and absenteeism. In turn, it hampers a positive therapeutic environment for youngsters. A method that may endorse a better work climate is Non-violent Resistance (NVR). As earlier research suggests that the residential NVR, adjusted for juveniles with MID, is successful in diminishing aggressive incidents and improving group climate, we hypothesize that NVR-MID will be also effective in enhancing work climate. We investigated the perception of work climate by staff of three residential settings before, during and after implementation of NVR-MID. Work climate was assessed both quantitatively and qualitatively. Outcomes were subsequently integrated. Quantitative data was collected using the Living Group Working Climate Inventory (LGWCI). Multilevel analyses were carried out to analyse the development of work climate over time. Qualitative data were collected via semi-structured interviews with NVR-MID trained staff and analysed through qualitative coding. Quantitative results showed that Job Satisfaction decreased after NVR-MID implementation. However, within qualitative reports, staff members experienced a positive influence on work climate of NVR-MID.

The alliance between the reigning quantum mechanical atom model and chemistry still is a difficult one when it comes to an adequate explanation for e.g. the covalent bond, inversion, chirality, or hydrogen bonds. Overruling Rutherford's extrapolation from gold to hydrogen, an atom model is described that provides improved answers to these phenomena while the hybridization principle and the covalent bond are re-defined by giving neutrons a much more prominent role than they have in the reigning quantum mechanical model. It is postulated that a neutron is not just there to assist the strong force in surpassing the repulsive coulombic forces between the protons in the nucleus, but the neutron is the modus operandi of molecular geometry, and as such plays a part in chemical reactivity, bond length and bond strength.

Clinical psychology finds itself with a paradox: On the one hand, there is abundant empirical evidence showing that aversive experiences increase the risk for psychopathology. In fact, a learning and memory framework forms the foundation of numerous psychological theories and treatments. For example, various CBT approaches aim to target maladaptive emotional memories (e.g., schemas or cognitions) that are deemed to lie at the core of mental health conditions. On the other hand, a new approach – the network theory – is gaining ground, which ignores underlying causes for mental disorders and instead dictates a focus on symptoms and their causal interactions. While radical shifts are sometimes necessary in science, we argue why completely neglecting common causes, such as emotional memory, is not justified. We critically discuss the strengths and limitations of the network approach: While its transdiagnostic nature and recognition of symptom interactions have the potential to invigorate the field, the framework is merely descriptive, its concepts not well defined, and its clinical utility still to be established. To move forward, we propose an incorporation of latent constructs into the network model, starting with clearer definitions and operationalisations of concepts in both network and latent variable models.

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.

Addition of hydrogen peroxide (H2O2) is a promising method to acutely suppress cyanobacterial blooms in lakes. However, a reliable H2O2 risk assessment to identify potential effects on non-target species is currently hampered by a lack of appropriate ecotoxicity data. The aim of the present study was therefore to quantify the responses of a wide diversity of freshwater phytoplankton, zooplankton and macroinvertebrates to H2O2 treatments of cyanobacterial blooms. To this end, we applied a multifaceted approach. First, we investigated the 24-h toxicity of H2O2 to three cyanobacteria (Planktothrix agardhii, Microcystis aeruginosa, Anabaena sp.) and 23 non-target species (six green algae, eight zooplankton and nine macroinvertebrate taxa), using EC50 values based on photosynthetic yield for phytoplankton and LC50 values based on mortality for the other organisms. The most sensitive species included all three cyanobacterial taxa, but also the rotifer Brachionus calyciflores and the cladocerans Ceriodaphnia dubia and Daphnia pulex. Next, the EC50 and LC50 values obtained from the laboratory toxicity tests were used to construct a species sensitivity distribution (SSD) for H2O2. Finally, the species predicted to be at risk by the SSD were compared with the responses of phytoplankton, zooplankton and macroinvertebrates to two whole-lake treatments with H2O2. The predictions of the laboratory-based SSD matched well with the responses of the different taxa to H2O2 in the lake. The first lake treatment, with a relatively low H2O2 concentration and short residence time, successfully suppressed cyanobacteria without major effects on non-target species. The second lake treatment had a higher H2O2 concentration with a longer residence time, which resulted in partial suppression of cyanobacteria, but also in a major collapse of rotifers and decreased abundance of small cladocerans. Our results thus revealed a trade-off between the successful suppression of cyanobacteria at the expense of adverse effects on part of the zooplankton community. This delicate balance strongly depends on the applied H2O2 dosage and may affect the decision whether to treat a lake or not.

In 2021 hebben meer mensen zich bij een Centrum voor Seksuele Gezondheid (CSG) laten testen op seksueel overdraagbare aandoeningen (soa) dan in 2020. Dit aantal is nog wel lager dan in 2019, het jaar voor de uitbraak van het coronavirus. Het percentage dat een soa had (20 procent) was lager dan in 2020, maar hoger dan in 2019. Mensen die een melding ontvingen voor een soa, hadden het vaakst infecties. Vanwege de coronacrisis evalueert het RIVM de ontwikkelingen van 2019-2021. Bij CSG's kunnen mensen met een grotere kans op soa, zich gratis laten testen. Sinds augustus 2019 bieden CSG's ook zorg aan mannen die seks hebben met mannen (MSM) en een geneesmiddel krijgen dat hiv voorkomt (Pre-Expositie Profylaxe, PrEP). Deze groep wordt elke drie maanden getest op soa's (MSM in de PrEP-pilot). In 2021 zijn in totaal 138.436 consulten geregistreerd bij de CSG's. Chlamydia In 2021 hadden 20.338 bezoekers aan de CSG's een chlamydia-infectie. Dat is bijna evenveel als in 2019 (21.123). Van het totaal aantal vrouwen dat zich liet testen bij de CSG's had 16,2 procent chlamydia. Van de heteroseksuele mannen was dat 21,3 procent. Deze percentages zijn lager dan in 2020, maar wel hoger dan in 2019. Van de MSM die zich lieten testen had 12,2 procent chlamydia. In 2019 was dat nog 10,6 procent. Onder MSM in de PrEP-pilot is het percentage chlamydia-diagnoses gedaald van 11,7 procent in 2019 naar 10 procent in 2021. Gonorroe Het aantal CSG-bezoekers dat in 2021 gonorroe had (7.842) was bijna hetzelfde als in 2019 (8.180). Van het totaal aantal vrouwen dat zich liet testen, had 1,5 procent deze soa. Van de heteroseksuele mannen was dat 1,8 procent. Deze percentages zijn licht gedaald, na een stijging in 2020, en lager dan in 2019. Het percentage gonorroe onder MSM steeg van 11,6 in 2019 naar 12,4 procent in 2021. Onder MSM in de PrEP-pilot daalde het percentage van 10,7 in 2019 naar 9,2 procent in 2021. Er is geen antibioticaresistentie tegen het huidige 'eerste keus' antibioticum voor gonorroe (ceftriaxon) gemeld. Syfilis In 2021 was het aantal CSG-bezoekers dat syfilis had (1.378) lager dan in 2019 (1.430). Het percentage MSM met syfilis was 2,6 procent in 2021, ongeveer hetzelfde als 2019 (2,5 procent). Onder MSM in de PrEP-pilot is dit percentage licht afgenomen van 2,2 procent in 2019 naar 1,7 procent in 2021. Het aantal diagnoses onder vrouwen en heteroseksuele mannen bleef in 2021 laag, respectievelijk 21 en 33. Hiv In 2021 kregen 128 CSG-bezoekers te horen dat ze hiv hebben, iets meer dan in 2020 (123). Onder hen waren 93 MSM en 17 deelnemers aan de PrEP-pilot. Er waren 6 vrouwen met hiv en 12 heteroseksuele mannen. In 2021, kwamen 794 mensen met hiv voor het eerst naar een hiv-behandelcentrum ('in zorg'). Dat was 18 procent minder dan in 2019 (972). PrEP In de nationale PrEP-pilot hebben 9.782 personen (van wie 97 procent MSM is) een eerste PrEP-consult gehad, van wie 3.450 in 2021. Op 31 december 2021 deden ongeveer 7.693 mensen mee aan de PrEP-pilot. Het percentage deelnemers met een soa was in 2021 17,7 procent.

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.

Background: The 6-month multicenter randomized controlled ALERTT1 trial showed improvement of time in range (TIR; 70-180 mg/dL) , HbA1c, time Methods: In this partial cross-over extension trial, the control group (n=127) switched as planned from isCGM to rtCGM from month 6 to month 24. The experimental group (n=127) continued rtCGM until month 24. Primary outcome was TIR. Key secondary outcomes were HbA1c, time Results: People in the trial were on average 42.9 years old; mean HbA1c was 7.4%. A minority used an insulin pump (n=49) or were hypo unaware (n=44) . TIR increased from 51.8% to 63.5% at month 12 in the former isCGM group (Δ 11.7% [9.6-13.8] P Conclusion: In adults with T1D, switching from isCGM to rtCGM is beneficial up to 24 months, adding further evidence that rtCGM with alerts is superior to isCGM without alerts. Disclosure M.M.Visser: Other Relationship; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dexcom, Inc., Novo Nordisk. N.Myngheer: Advisory Panel; AstraZeneca, Speaker's Bureau; AstraZeneca, Novo Nordisk. C.F.Vercammen: Other Relationship; AstraZeneca. F.Nobels: Advisory Panel; Abbott Diabetes, AstraZeneca. B.Keymeulen: None. C.Mathieu: Advisory Panel; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Imcyse, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca. P.Gillard: Advisory Panel; Bayer AG, Novo Nordisk, Speaker's Bureau; Abbott Diabetes, Bayer AG, Dexcom, Inc., Insulet Corporation, Medtronic, Novo Nordisk, Roche Diabetes Care, Sanofi. S.Charleer: None. S.Fieuws: None. C.De block: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk, Research Support; Indigo Diabetes, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk. R.Hilbrands: None. L.Van huffel: Advisory Panel; Roche Diagnostics, Other Relationship; Medtronic, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk. T.Maes: None. G.Vanhaverbeke: Advisory Panel; Abbott Diabetes, AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp., Speaker's Bureau; Novo Nordisk, Sanofi. E.L.Dirinck: None. Funding Dexcom, San Diego, CA, USA (OUS-2018-011)

In the near-future, dedicated telescopes observe Earth-like exoplanets in reflected light, allowing their characterization. Because of the huge distances, every exoplanet will be a single pixel, but temporal variations in its spectral flux hold information about the planet's surface and atmosphere. We test convolutional neural networks for retrieving a planet's rotation axis, surface and cloud map from simulated single-pixel flux and polarization observations. We investigate the assumption that the planets reflect Lambertian in the retrieval while their actual reflection is bidirectional, and of including polarization in retrievals. We simulate observations along a planet's orbit using a radiative transfer algorithm that includes polarization and bidirectional reflection by vegetation, desert, oceans, water clouds, and Rayleigh scattering in 6 spectral bands from 400 to 800 nm, at various photon noise levels. The surface-types and cloud patterns of the facets covering a model planet are based on probability distributions. Our networks are trained with simulated observations of millions of planets before retrieving maps of test planets. The neural networks can constrain rotation axes with a mean squared error (MSE) as small as 0.0097, depending on the orbital inclination. On a bidirectionally reflecting planet, 92% of ocean and 85% of vegetation, desert, and cloud facets are correctly retrieved, in the absence of noise. With realistic noise, it should still be possible to retrieve the main map features with a dedicated telescope. Except for face-on orbits, a network trained with Lambertian reflecting planets, yields significant retrieval errors when given observations of bidirectionally reflecting planets, in particular, brightness artefacts around a planet's pole. Including polarization improves retrieving the rotation axis and the accuracy of the retrieval of ocean and cloud facets., 38 pages, 25 figures, 5 tables, accepted for publication in Astron. Astrophys

Attributing intentions to others’ actions is important for learning to avoid their potentially harmful consequences. Here, we used functional magnetic resonance imaging multivariate pattern analysis to investigate how the brain integrates information about others’ intentions with the aversive outcome of their actions. In an interactive aversive learning task, participants (n = 33) were scanned while watching two alleged coparticipants (confederates)—one making choices intentionally and the other unintentionally—leading to aversive (a mild shock) or safe (no shock) outcomes to the participant. We assessed the trial-by-trial changes in participants’ neural activation patterns related to observing the coparticipants and experiencing the outcome of their choices. Participants reported a higher number of shocks, more discomfort, and more anger to shocks given by the intentional player. Intentionality enhanced responses to aversive actions in the insula, anterior cingulate cortex, inferior frontal gyrus, dorsal medial prefrontal cortex, and the anterior superior temporal sulcus. Our findings indicate that neural pattern similarities index the integration of social and threat information across the cortex.

Incidence of subclinical hypocalcemia in early postpartum dairy cows continues to be an animal welfare concern and an economic burden for producers. Feeding prepartum negative dietary cation-anion difference (DCAD) diets produces metabolic acidosis, which supports mobilization of bone calcium and reduces the incidence of hypocalcemia. Achieving a sufficient degree of metabolic acidosis without reducing dry matter intake (DMI) can be difficult. This study compared the ability of MegAnion (MA; Origination O2D Inc., Maplewood, MN), a new DCAD supplement designed to be more palatable than typical anionic salt sources, and another palatable commercial DCAD product, SoyChlor (SC; Landus Cooperative, Ralston, IA), to reduce urine pH (a surrogate for metabolic acidosis) without reducing prepartum DMI. A secondary objective was to assess the effect of these anionic supplements on postpartum serum calcium concentrations and DMI. Prepartum multiparous Holstein (HO) and crossbred (XX) cows were blocked by breed and expected calving date and randomly assigned within breed to total mixed rations (TMR) with MA or SC and DCAD values of -215 mEq/kg of DM. Cows (n = 56; 15 MA-HO, 12 SC-HO, 15 MA-XX, 14 SC-XX) consumed the treatment TMR for at least 19 d and completed the 28 d in milk (DIM) phase of the study. Urine and blood samples were collected weekly and at 1, 2, and 3 DIM. Data were analyzed as a randomized block design by repeated measures with week or DIM as the repeated effect. Prepartum urine pH decreased from 8.15 ± 0.27 before treatment to 6.12 ± 0.14 during treatment, was not affected by anionic supplement, and increased immediately after calving when all cows consumed the same early-lactation TMR. Prepartum serum calcium concentrations were not affected (2.34 vs. 2.33 ± 0.02 mmol/L) by treatment, whereas nonesterified fatty acids were lower (86 vs. 120 ± 10 mmol/L) and insulin was greater (215 vs. 174 ± 10 pmol/L) in cows fed MA than in cows fed SC. These differences are supported by the numerically greater prepartum DMI (1.2 kg/d) and energy balance (1.8 Mcal/d) of cows fed MA. However, pre- and postpartum DMI and other production variables, including body weight, body condition score, milk yield, and energy balance, were not affected by treatment. This lack of difference indicates that MA provides another effective source of anionic salts for diets designed to reduce urine pH and induce metabolic acidosis in prepartum dairy cows.

Willen huisartsen goede zorg leveren, dan is reflectie op hun eigen handelen in de praktijk essentieel. Externe feedback zet helaas niet altijd aan tot reflectie en duurzame zorgverbetering. In een groep samen reflecteren op spiegelinformatie kan wel motiveren tot gedragsverandering en uiteindelijk tot het optimaliseren van de zorg. Hoe gezamenlijke reflectie van vandaag kan leiden tot een concrete aanpassing van het handelen van morgen.

Usutu 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 General Practitioners (GPs) and Practice Nurses (PNs) collaboratively play an important role in preventing and monitoring chronic diseases. They are trained in Motivational Interviewing (MI), which is a communication style to intrinsically motivate patients to a healthier lifestyle. However, being trained in MI skills does not necessarily mean that it is implemented in daily practice so patients actually benefit. The aim of this study is to identify factors that facilitate or impede the implementation of MI in General Practice. Methods A total of 152 participants (93 GP-trainees and 59 PN-trainees) who were trained in MI completed a questionnaire regarding the implementation of MI. Semi-structured interviews (N = 17) were conducted with GPs and PNs (ranging from almost graduated to highly experienced) who were selected through the process of maximum variation sampling. The interview guide was based on the five-stage implementation model of Grol and Wensing. Results Thirteen factors that influence the implementation of MI in General Practice were identified. They can be allocated to three categories: (1) setting factors such as time, (2) GP/PN factors such as self-efficacy, and (3) patient factors such as cultural background. Conclusions Overall, GPs and PNs considered MI to be useful and part of their professional responsibility. Most difficulties become apparent in stage 4 (change: applying MI skills in practice) and 5 (consolidation: integrating MI into daily routine and embedment in organisation) of Grol and Wensing’s model. Therefore, it is important that training does not only focus on MI skills. It is essential to pay explicit attention to the factors that impact implementation, as well as the appropriate tools to tackle the barriers. These insights can help trainers to effectively support GPs and PNs to apply and maintain their MI skills in daily practice.

In a Keplerian system, a large number of bodies orbit a central mass. Accretion disks, protoplanetary disks, asteroid belts, and planetary rings are examples. Simulations of these systems require algorithms that are computationally efficient. The inclusion of collisions in the simulations is challenging but important. We intend to calculate the time of collision of two astronomical bodies in intersecting Kepler orbits as a function of the orbital elements. The aim is to use the solution in an analytic propagator ($N$-body simulation) that jumps from one collision event to the next. We outline an algorithm that maintains a list of possible collision pairs ordered chronologically. At each step (the soonest event on the list), only the particles created in the collision can cause new collision possibilities. We estimate the collision rate, the length of the list, and the average change in this length at an event, and study the efficiency of the method used. We find that the collision-time problem is equivalent to finding the grid point between two parallel lines that is closest to the origin. The solution is based on the continued fraction of the ratio of orbital periods. Due to the large jumps in time, the algorithm can beat tree codes (octree and $k$-d tree codes can efficiently detect collisions) for specific systems such as the Solar System with $N, 15 pages, 14 figures

The importance of soils to society has gained increasing recognition over the past decade, with the potential to contribute to most of the United Nations’ Sustainable Development Goals (SDGs). With unprecedented and growing demands for food, water and energy, there is an urgent need for a global effort to address the challenges of climate change and land degradation, whilst protecting soil as a natural resource. In this paper, we identify the contribution of soil science over the past decade to addressing gaps in our knowledge regarding major environmental challenges: climate change, food security, water security, urban development, and ecosystem functioning and biodiversity. Continuing to address knowledge gaps in soil science is essential for the achievement of the SDGs. However, with limited time and budget, it is also pertinent to identify effective methods of working that ensure the research carried out leads to real-world impact. Here, we suggest three strategies for the next decade of soil science, comprising a greater implementation of research into policy, interdisciplinary partnerships to evaluate function trade-offs and synergies between soils and other environmental domains, and integrating monitoring and modelling methods to ensure soil-based policies can withstand the uncertainties of the future. Highlights: We highlight the contributions of soil science to five major environmental challenges since 2010. Researchers have contributed to recommendation reports, but work is rarely translated into policy. Interdisciplinary work should assess trade-offs and synergies between soils and other domains. Integrating monitoring and modelling is key for robust and sustainable soils-based policymaking.

A myriad of clinical theories places emotional memory or mental representations at the root of mental disorders. Various cognitive-behavioural interventions are based on the assumption that targeting the underlying emotional memory is the working mechanism of treatment efficacy. To test the assumptions about the role of emotional memory in the development, maintenance, and treatment of mental disorders, we first need to establish ecologically valid paradigms that can induce emotional memory in the lab. For this, we used the Trier Social Stress Test (TSST), a standardized protocol to elicit social distress, paired with a neutral unfamiliar ambient odour, to create a sensory-rich and personally meaningful episodic experience. Seven days later, participants (N = 132) reactivated the memory of the TSST with the aid of auditory, olfactory, and visual retrieval cues, during which their heart rate and self-reported affective responses were collected. Although increases in heart rate were only observed during encoding, and not at retrieval, self-report ratings showed that cues which directly referred to the aversive experience evoked more negative valence, arousal, and feelings of lack of control during memory reactivation compared to control cues across sensory modalities. These findings are indicative of successful memory induction and corroborate the utility of ambient odours as retrieval aids. Moreover, the self-reported response to the reactivated emotional memory correlated with individual differences in indices of (social) anxiety and depression. Thereby, we provide preliminary evidence of the translational significance of this paradigm that offers potential for being a model to induce ecologically valid emotional memory in the lab.

ObjectivesThere 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.DesignAn 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.SettingGeneral practice in the Netherlands.Participants22 participants were purposively sampled for eight interviews and two focus group discussions.ResultsThree 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.ConclusionsPeer 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.

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.

While eutrophication remains one of the main pressures acting on freshwater ecosystems, the prevalence of anthropogenic and nature-induced stochastic pulse perturbations is predicted to increase due to climate change. Despite all our knowledge on the effects of eutrophication and stochastic events operating in isolation, we know little about how eutrophication may affect the response and recovery of aquatic ecosystems to pulse perturbations. There are multiple ways in which eutrophication and pulse perturbations may interact to induce potentially synergic changes in the system, for instance, by increasing the amount of nutrients released after a pulse perturbation. Here, we performed a controlled press and pulse perturbation experiment using mesocosms filled with natural lake water to address how eutrophication modulates the phytoplankton response to sequential mortality pulse perturbations; and what is the combined effect of press and pulse perturbations on the resistance and resilience of the phytoplankton community. Our experiment showed that eutrophication increased the

Evolution is a key process by which populations can adapt to novel conditions, but it is not well understood how predictable this process is. Predictability is expected to depend on the ratio of deterministic and stochastic processes that contribute to evolutionary change and this ratio is modulated by the effective population size. Smaller effective populations harbor less genetic diversity and stochastic processes are generally expected to play a larger role, leading to less repeatable evolutionary trajectories. Empirical insight into the relationship between effective population size and repeatability is limited and biased towards asexual unicellular organisms. Here, we used populations of obligately outcrossing Caenorhabditis elegans to test whether fitness increase and selection response were more heterogeneous after a moderate or strong population bottleneck compared to a scenario without bottleneck. Nematodes were exposed to a novel bacterial prey and lower temperature. Population sizes after one week of growth (as a proxy of fitness) were measured before and after 15 generations of evolution. We found that replicates across all (no/moderate/strong bottleneck) treatments evolved higher fitness and no significant difference in average or maximum fitness was found among treatments. Partitioning fitness variance among effects from selection and effects from chance showed that a strong (but not a moderate) bottleneck reduced the relative contribution of selection effects to fitness variation. However, the reduced contribution from selection did not translate to a significant reduction in the repeatability of fitness evolution. Thus, although a strong bottleneck reduced the contribution of deterministic evolutionary change, we found only marginal effects on quantitative measurements of repeatability in evolution. We conclude that the extent to which evolution is predictable may not universally depend on effective population size. IMPACT SUMMARYEvolution is a key process by which populations can adapt to novel conditions. The predictability of evolution is elusive, but the extent to which evolution is predictable is central to our understanding of evolutionary processes and to emergent applications in medicine, agriculture, and conservation. Predictability is expected to be high when evolutionary change is mainly driven by selection, because this leads to repeatable evolutionary trajectories. However, chance effects, e.g. from genetic drift, reduce repeatability. In populations with smaller effective sizes (and thus reduced genetic diversity), chance effects are generally thought to be more prevalent than in large effective populations, suggesting that effective population size influences evolutionary repeatability. Recent theoretical insights cast doubt on the universality of this relationship between evolutionary repeatability and effective population size. Thus far, empirical work testing these theoretical insights is limited to asexual species, leaving a gap in our knowledge. Therefore, we performed an evolutionary experiment using sexually reproducing populations of the nematode Caenorhabditis elegans. Populations either went through a strong or moderate bottleneck or through no bottleneck at all to create populations with different degrees of genetic variation. These populations with different histories (but similar census size) were then exposed to novel conditions. Our results showed that neither average fitness in the novel environment or the repeatability of fitness evolution were significantly lower following a bottleneck. This was despite a reduced contribution from selection and increased contribution from chance to fitness variation in populations that experienced a strong bottleneck. We therefore show that in sexually reproducing species, increased contributions from chance in populations with lower effective sizes do not necessarily affect evolutionary repeatability. This is an important novel insight that is relevant both for our fundamental understanding as well as for evolutionary forecasting applications in agriculture and conservation, which are primarily targeted at sexual species.

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.