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The common house mosquito ( Culex pipiens ) is a native vector for West Nile virus (WNV). Invasive species like the tiger mosquito ( Aedes albopictus ) and Asian bush mosquito ( Aedes japonicus ) are rapidly spreading through Europe, posing a major threat as vectors for dengue, chikungunya (CHIKV), and Japanese encephalitis virus (JEV). These mosquitoes share a similar ecological niche as larvae, but the carry-over effects of aquatic larval interactions to the terrestrial adult stage remain largely unknown and their medical relevance requires further investigation. This study examines the context dependency of larval interactions among Aedes albopictus , Aedes japonicus , and Culex pipiens . The survival, development time, growth, and energetic storage were measured in different European populations within density-response (intraspecific) experiments and replacement (interspecific) experiments at 20 °C and 26 °C. Overall, Ae. japonicus was the weakest competitor, while competition between Ae. albopictus and Cx. pipiens varied with temperature. Adults emerging from this larval competition were infected as follows: Culex pipiens with WNV, Ae. albopictus with CHIKV, and Ae. japonicus with JEV. While no JEV infection was observed, mosquitoes experiencing interspecific interactions during their larval stages exhibited higher infection rates and viral RNA titers for CHIKV and WNV. This increased susceptibility to viral infection after larval competition suggests a higher risk of arbovirus transmission in co-occurring populations.

Objective: To establish a set of clinician and patient-reported outcome measures (PROMs) and present the initial findings of a value-based healthcare (VBHC) program in patients with premature ovarian insufficiency (POI)., Methods: Employing a four-phase approach, we identified the most crucial domains for patients with POI and translated these into PROMs. Prior to each visit, patients completed questionnaires to evaluate: depression (BDI-II), menopausal symptoms (GCS), work ability (WAS) and infertility (FertiQoL). During the visits, cardiovascular health assessments and dual-energy X-ray absorptiometry (DEXA) scans to measure bone mineral density were performed. Data at intake is presented, and comparisons are drawn between women using and those not using hormone replacement therapy (HRT). Patient-reported experience measures (PREMs) were evaluated by a questionnaire., Results: A total of 267 POI patients completed the PROM questionnaires, of whom 58.1 % were using HRT at intake. Over half of the patients (53.5 %), had a BDI-II score of 14 or higher, indicating mild to severe depression. The mean total GCS score was 20.9 (SD 11.3). The median work ability score was 7.5 (IQR 6.0-8.0) and the mean FertiQoL score 63.9 (SD 15.7). Additionally, 22.7 % of patients presented with hypertension, 6.2 % with hypercholesterolemia, and almost 50 % had low bone mass. Patients rated the VBHC program with a mean of 8.6 (SD 1.2)., Conclusions: These findings underscore the necessity of a multidisciplinary VBHC program incorporating standardized screening and psychological treatment. We advocate for the implementation of patient-centered outcomes for clinical practice, which have been found to be highly relevant by patients with POI., Competing Interests: Declaration of competing interest G. Jiskoot received an unrestricted research grant from the Waterloo Foundation and she received consultancy fees from Ferring. Y.V. Louwers received an internal research grant from the Erasmus MC (The Synergy grant) and she received fees from Ferring and Merck for presentations. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Premature ovarian insufficiency (POI) is a rare condition characterized by loss of ovarian function before the age of 40. POI seems associated with mood disorders and sexual dysfunction. However, there is a lack of high-quality evidence relating to the impact of POI on sexual function. Therefore, we conducted a systematic review and meta-analysis to evaluate sexual function in women with POI compared to women without the condition. The following online databases were systematically searched up to January 2023: EMBASE, Medline (Ovid), Web of Science, Cochrane, PsychInfo, and Google Scholar. Random effects models were used for analyses, with data reported as Hedges' g and 95 % confidence interval, and the risk of heterogeneity was evaluated. The protocol of this study was registered with PROSPERO (CRD42023437203). A total of 10 studies were included in the systematic review and 5 studies involving 352 women with POI were included in the meta-analysis. Eight of the ten studies concluded that women with POI have reduced sexual function. An overall medium Hedges' g effect size of -0.72 was found (ranging between -0.20 and -1.29) in favor of control women, with moderate heterogeneity (I 2  = 64 %). Stratified studies of women on systemic hormone replacement therapy (HRT) showed an even higher Hedges' g effect size, of -0.82 (95 % CI -1.18, -0.47). In conclusion, sexual function in women with POI is reduced compared with control women. Sexual function should be discussed with women with POI and they should be offered psychosexual counseling., Competing Interests: Declaration of competing interest G. Jiskoot received an unrestricted research grant from the Waterloo Foundation and she received consultancy fees from Ferring. Y.V. Louwers received an internal research grant from the Erasmus MC (The Synergy grant) and she received fees from Ferring and Merck for presentations. J.L. reports grants from Ansh Labs, Webster, Tx, USA, from Ferring, Hoofddorp, NL, from Dutch Heart Association, Utrecht, NL, from Zon MW, Amsterdam, NL, from Roche Diagnostics, Rothkreuz, Switzerland and personal fees from Ferring, Hoofddorp, NL, from Titus Healthcare, Hoofddorp, NL, from Gedeon Richter, Groot-Bijgaarden, Belgium, and is an unpaid board member and president of the AE-PCOS Society, outside the submitted work. The author(s) declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Human pluripotent stem cell (hPSC) cultures are prone to genetic drift, because cells that have acquired specific genetic abnormalities experience a selective advantage in vitro. These abnormalities are highly recurrent in hPSC lines worldwide, but their functional consequences in differentiating cells are scarcely described. In this work, we show that the loss of chromosome 18q impairs neuroectoderm commitment and that downregulation of SALL3, a gene located in the common 18q loss region, is responsible for this failed neuroectodermal differentiation. Knockdown of SALL3 in control lines impaired differentiation in a manner similar to the loss of 18q, and transgenic overexpression of SALL3 in hESCs with 18q loss rescued the differentiation capacity of the cells. Finally, we show that loss of 18q and downregulation of SALL3 leads to changes in the expression of genes involved in pathways regulating pluripotency and differentiation, suggesting that these cells are in an altered state of pluripotency., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Besides age, estrogen exposure plays a crucial role in changes in bone density (BD) in women. Premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS) are conditions in reproductive-aged women in which the exposure to estrogen is substantially different. Women with a history of preeclampsia (PE) are expected to have normal estrogen exposure. Within the CREw-IMAGO study, we investigated if trabecular BD is different in these women because of differences in the duration of estrogen exposure. Trabecular BD was measured in thoracic vertebrae on coronary CT scans. Women with an reduced estrogen exposure (POI) have a lower BD compared to women with an intermediate exposure (PE) (mean difference (MD) -26.8, 95% confidence interval (CI) -37.2 - -16.3). Women with a prolonged estrogen exposure (PCOS) have the highest BD (MD 15.0, 95% CI 4.3 - 25.7). These results support the hypothesis that the duration of estrogen exposure in these women is associated with trabecular BD.

As Africa is facing multiple challenges related to food security, frameworks integrating production and availability are urgent for policymaking. Attention should be given not only to gradual socio-economic and climatic changes but also to their temporal variability. Here we present an integrated framework that allows one to assess the impacts of socio-economic development, gradual climate change and climate anomalies. We apply this framework to rice production and consumption in Africa whereby we explicitly account for the continent's dependency on imported rice. We show that socio-economic development dictates rice availability, whereas climate change has only minor effects in the long term and is predicted not to amplify supply shocks. Still, rainfed-dominated or self-producing regions are sensitive to local climatic anomalies, while trade dominates stability in import-dependent regions. Our study suggests that facilitating agricultural development and limiting trade barriers are key in relieving future challenges to rice availability and stability., (© 2023. The Author(s).)

Background: As in other domains of medicine, high-throughput sequencing methods have led to the identification of an ever-increasing number of gene variants in the fields of both male and female infertility. The increasing number of recently identified genes allows an accurate diagnosis for previously idiopathic cases of female infertility and more appropriate patient care. However, robust evidence of the gene-disease relationships (GDR) allowing the proper translation to clinical application is still missing in many cases., Objective and Rationale: An evidence-based curation of currently identified genes involved in female infertility and differences in sex development (DSD) would significantly improve both diagnostic performance and genetic research. We therefore performed a systematic review to summarize current knowledge and assess the available GDR., Search Methods: PRISMA guidelines were applied to curate all available information from PubMed and Web of Science on genetics of human female infertility and DSD leading to infertility, from 1 January 1988 to 1 November 2021. The reviewed pathologies include non-syndromic as well as syndromic female infertility, and endocrine and reproductive system disorders. The evidence that an identified phenotype is caused by pathogenic variants in a specific gene was assessed according to a standardized scoring system. A final score (no evidence, limited, moderate, strong, or definitive) was assigned to every GDR., Outcomes: A total of 45 271 publications were identified and screened for inclusion of which 1078 were selected for gene and variant extraction. We have identified 395 genes and validated 466 GDRs covering all reported monogenic causes of female infertility and DSD. Furthermore, we present a genetic diagnostic flowchart including 105 genes with at least moderate evidence for female infertility and suggest recommendations for future research. The study did not take into account associated genetic risk factor(s) or oligogenic/polygenic causes of female infertility., Wider Implications: We have comprehensively reviewed the existing research on the genetics of female infertility and DSD, which will enable the development of diagnostic panels using validated genes. Whole genome analysis is shifting from predominantly research to clinical application, increasing its diagnostic potential. These new diagnostic possibilities will not only decrease the number of idiopathic cases but will also render genetic counselling more effective for infertile patients and their families., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Developing and integrating agricultural markets may be key to addressing Africa's sustainability challenges. By modelling trade costs from farm gate to potential import markets across eight African regions, we investigate the impact of individual components of continental free trade and the complementary role of domestic agricultural development through increased market access for farmers and agricultural intensification. We find that free trade would increase intra-African agricultural trade sixfold by 2030 but-since it does not address local supply constraints-outside food imports and undernourishment would reduce only marginally. Agricultural development could almost eliminate undernourishment in Africa by 2050 at only a small cost of increased global greenhouse gas emissions. While continental free trade will be enabled in Africa through the African Continental Free Trade Area, aligning this with local agricultural development policies is crucial to increase intra-African trade gains, promote food security and achieve climate objectives., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To determine the prevalence of incidental findings (IFs) on coronary computed tomography (CCT) in women aged 45-55 years and previously diagnosed with reproductive disorders such as polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI) or preeclampsia (PE)., Methods: A total of 486 middle-aged women with PCOS (n = 101), POI (n = 97) or a history of PE (n = 288) underwent a CCT as part of a prior prospective study. IFs were categorized by their significance (minor, moderate and major). Follow-up information was collected from patients' records. To investigate the impact of different field of views (FOVs), a subset of scans was analyzed in full FOV and small FOV., Results: In 96/486 (19.8%) women, one or more IFs were detected, of which 54/486 (11.1%) were classified as moderate/major and 48/486 (9.9%) required follow-up. A moderate/major IF was detected in 16/101 (15.9%) women with PCOS, 13/97 (13.4%) women with POI and 25/288 (8.7%) women with a history of PE. In 78 women with an IF detected in the full FOV, the IF was still visible in 60 (76.9%) women in the small FOV. In the full FOV, 46 women required follow-up, but using the small FOV this was reduced to 30 women., Conclusion: Using CCT as a cardiovascular disease screening tool in women with selected reproductive disorders increases the probability of detecting IFs that can cause anxiety and may generate extra costs, but can also reveal clinically relevant findings. Using a small FOV centered around the heart resulted in a lower prevalence of IFs and required less follow-up., (© 2022. The Author(s).)

Importance: Exposure to phthalates may affect fetal growth, but previous studies are inconsistent and have not explored the trimester-specific effects of phthalates on repeated measures of fetal growth., Objective: To assess the associations of maternal phthalate metabolites urine concentrations with fetal growth measures and birth outcomes and identify potential windows of vulnerability to exposure., Design: Population-based prospective cohort study, the Generation R Study (2002-2006). Data analysis was performed from November 2019 to June 2020., Setting: Rotterdam, the Netherlands., Participants: 1379 pregnant women., Exposures: Maternal phthalate metabolites urine concentrations in first, second and third trimester., Main Outcomes and Measures: Fetal head circumference, length and weight measured in the second and third trimester by ultrasound and at birth and preterm birth and small size for gestational age at birth., Results: Higher pregnancy-averaged phthalic acid, low molecular weight phthalate (LMWP), high molecular weight phthalate (HMWP) and di-2-ethylhexylphthalate (DEHP) concentrations tended to be associated with lower fetal weight SDS across gestation. The associations of phthalic acid and LMWP with fetal weight became stronger as pregnancy progressed (differences -0.08 (95% CI -0.14 to -0.02) SDS and -0.09 (95% CI -0.16 to -0.02) SDS at 40 weeks per interquartile range increase in phthalic acid and LMWP, respectively). Higher concentrations of specific LMWP, HMWP and DEHP metabolites were also associated with smaller head circumference and lower length SDS at birth and an increased risk of preterm birth and small size for gestational age at birth (p-values < 0.05). We observed differences by timing of exposure in these associations., Conclusions and Relevance: Higher maternal phthalate metabolites urine concentrations seem to be related with fetal growth restriction and preterm birth. Phthalates may have trimester specific effects on fetal growth and birth outcomes. Further studies are needed to explore the underlying mechanisms and long-term consequences., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Exposure to bisphenols may affect fetal growth and development. The trimester-specific effects of bisphenols on repeated measures of fetal growth remain unknown. Our objective was to assess the associations of maternal bisphenol urine concentrations with fetal growth measures and birth outcomes and identify potential critical exposure periods., Methods: In a population-based prospective cohort study among 1379 pregnant women, we measured maternal bisphenol A, S and F urine concentrations in the first, second and third trimester. Fetal head circumference, length and weight were measured in the second and third trimester by ultrasound and at birth., Results: An interquartile range increase in maternal pregnancy-averaged bisphenol S concentrations was associated with larger fetal head circumference (difference 0.18 (95% confidence interval (CI) 0.01 to 0.34) standard deviation scores (SDS), p-value< 0.05) across pregnancy. When focusing on specific critical exposure periods, any detection of first trimester bisphenol S was associated with larger second and third trimester fetal head circumference (difference 0.15 (95% CI 0.05 to 0.26) and 0.12 (95% CI 0.02 to 0.23) SDS, respectively) and fetal weight (difference 0.12 (95% CI 0.02 to 0.22) and 0.16 (95% CI 0.06 to 0.26) SDS, respectively). The other bisphenols were not consistently associated with fetal growth outcomes. Any detection of bisphenol S and bisphenol F in first trimester was also associated with a lower risk of being born small size for gestational age (Odds Ratio 0.56 (95% CI 0.38 to 0.74) and 0.55 (95% CI 0.36 to 0.85), respectively). Bisphenols were not associated with risk of preterm birth., Conclusions: Higher maternal bisphenol S urine concentrations, especially in the first trimester, seem to be related with larger fetal head circumference, higher weight and a lower risk of being small size for gestational age at birth.

International trade enables us to exploit regional differences in climate change impacts and is increasingly regarded as a potential adaptation mechanism. Here, we focus on hunger reduction through international trade under alternative trade scenarios for a wide range of climate futures. Under the current level of trade integration, climate change would lead to up to 55 million people who are undernourished in 2050. Without adaptation through trade, the impacts of global climate change would increase to 73 million people who are undernourished (+33%). Reduction in tariffs as well as institutional and infrastructural barriers would decrease the negative impact to 20 million (-64%) people. We assess the adaptation effect of trade and climate-induced specialization patterns. The adaptation effect is strongest for hunger-affected import-dependent regions. However, in hunger-affected export-oriented regions, partial trade integration can lead to increased exports at the expense of domestic food availability. Although trade integration is a key component of adaptation, it needs sensitive implementation to benefit all regions., Competing Interests: Competing interests The authors declare no competing interests.

Background: Exposure to bisphenols and phthalates might influence bone health. We hypothesized that exposure to bisphenols and phthalates during fetal life has persistent effects on bone development., Objectives: To analyze the associations of fetal exposure to bisphenols and phthalates with bone health in school-aged children., Methods: Among 1,362 mother-child pairs participating in a population-based cohort study, we measured maternal urinary concentrations of bisphenols and phthalates at first, second and third trimester with high performance liquid chromatography electrospray ionization-tandem mass spectrometry. Total body bone mineral density (BMD) and bone area (BA) were measured using dual-energy X-ray absorptiometry (DXA) at 6 and 10 years, and were both used to calculate bone mineral content (BMC) and area-adjusted BMC (aBMC, a measure of volumetric BMD)., Results: Maternal bisphenol concentrations were not associated with childhood bone measures at 6 years. After adjustment for covariates and multiple testing correction, an interquartile range increase in maternal first trimester bisphenol S (BPS) concentrations was associated with lower BMD and aBMC at 10 years (-6.08 (95% confidence interval (CI), -9.97 to -2.19) mg/cm 2 and -0.12 (95% CI, -0.20 to -0.04) g). Maternal third trimester low molecular weight (LMW) phthalate concentrations were associated with higher aBMC at 6 years whereas, maternal third trimester di-n-octylphthalate (DNOP) concentrations were associated with lower aBMC at 10 years. However, these associations did not remain statistically significant after multiple testing correction., Discussion: Maternal first trimester BPS concentrations are associated with lower BMD and aBMC in school-aged children. These findings should be considered as hypothesis generating and need further replication and exploration of potential underlying mechanisms., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

A study of 3,500 children in the UK shows that data on socioeconomic background and previous educational achievements can better predict how students will perform at school than genetic data., Competing Interests: CJ No competing interests declared, (© 2020, Janssens.)

Based on reward and difficulty information, people can strategically adjust proactive cognitive control. fMRI research shows that motivated proactive control is implemented through fronto-parietal control networks that are triggered by reward and difficulty cues. Here, we investigate electrophysiological signatures of proactive control. Previously, the contingent negative variation (CNV) in the ERPs and oscillatory power in the theta (4-8 Hz) and alpha band (8-14 Hz) have been suggested as signatures of control implementation. However, experimental designs did not always separate control implementation from motor preparation. Critically, we used a mental calculation task to investigate effects of proactive control implementation on the CNV and on theta and alpha power, in absence of motor preparation. In the period leading up to task onset, we found a more negative CNV, increased theta power, and decreased alpha power for hard versus easy calculations, showing increased proactive control implementation when a difficult task was expected. These three measures also correlated with behavioral performance, both across trials and across subjects. In addition to scalp EEG in healthy participants, we collected intracranial local field potential recordings in an epilepsy patient. We observed a slow-drift component that was more pronounced for hard trials in a hippocampal location, possibly reflecting task-specific preparation for hard mental calculations. The current study thus shows that difficulty information triggers proactive control in absence of motor preparation and elucidates its neurophysiological signatures., (© 2019 Society for Psychophysiological Research.)

Reward prediction errors (RPEs) are crucial to learning. Whereas these mismatches between reward expectation and reward outcome are known to drive procedural learning, their role in declarative learning remains underexplored. Earlier work from our lab addressed this, and consistently found that signed reward prediction errors (SRPEs; "better-than-expected" signals) boost declarative learning. In the current EEG study, we sought to explore the neural signatures of SRPEs. Participants studied 60 Dutch-Swahili word pairs while RPE magnitudes were parametrically manipulated. Behaviorally, we replicated our previous findings that SRPEs drive declarative learning, with increased recognition for word pairs accompanied by large, positive RPEs. In the EEG data, at the start of reward feedback processing, we found an oscillatory (theta) signature consistent with unsigned reward prediction errors (URPEs; "different-than-expected" signals). Slightly later during reward feedback processing, we observed oscillatory (high-beta and high-alpha) signatures for SRPEs during reward feedback, similar to SRPE signatures during procedural learning. These findings illuminate the time course of neural oscillations in processing reward during declarative learning, providing important constraints for future theoretical work., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Stimulus complexity is an important determinant of aesthetic preference. An influential idea is that increases in stimulus complexity lead to increased preference up to an optimal point after which preference decreases (inverted-U pattern). However, whereas some studies indeed observed this pattern, most studies instead showed an increased preference for more complexity. One complicating issue is that it remains unclear how to define complexity. To address this, we approached complexity and its relation to aesthetic preference from a predictive coding perspective. Here, low- and high-complexity stimuli would correspond to low and high levels of prediction errors, respectively. We expected participants to prefer stimuli which are neither too easy to predict (low prediction error), nor too difficult (high prediction error). To test this, we presented two sequences of tones on each trial that varied in predictability from highly regular (low prediction error) to completely random (high prediction error), and participants had to indicate which of the two sequences they preferred in a two-interval forced-choice task. The complexity of each tone sequence (amount of prediction error) was estimated using entropy. Results showed that participants tended to choose stimuli with intermediate complexity over those of high or low complexity. This confirms the century-old idea that stimulus complexity has an inverted-U relationship to aesthetic preference., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Recent associative models of cognitive control hypothesize that cognitive control can be learned (optimized) for task-specific settings via associations between perceptual, motor, and control representations, and, once learned, control can be implemented rapidly. Midfrontal brain areas signal the need for control, and control is subsequently implemented by biasing sensory representations, boosting or suppressing activity in brain areas processing task-relevant or task-irrelevant information. To assess the timescale of this process, we employed EEG. In order to pinpoint control implementation in specific sensory areas, we used a flanker task with incongruent flankers shown in only one hemifield (congruent flankers in the other hemifield) isolating their processing in the contralateral hemisphere. ERPs revealed fast modulations specifically in visual processing areas contralateral to the incongruent flankers. To test whether these modulations reflect increased or decreased processing of incongruent flankers, we investigated alpha power, a marker for attentional inhibition. Importantly, we show increased alpha power over visual areas processing incongruent flankers from 300 to 500 ms poststimulus onset. This suggests fast cognitive control by attentional inhibition for information disrupting goal-oriented actions. Additionally, we show that midfrontal theta earlier in the trial is also modulated by incongruency, and that theta power predicts subsequent alpha power modulations. This supports the hypothesis that midfrontal incongruency detection leads to control implementation, and reveals that these mechanisms take place on a fast, within-trial timescale., (© 2017 Society for Psychophysiological Research.)

Objectives: To assess the effect on needed nursing time for dressing change., Design, Setting, Participants: A parallel-group, open-label, randomised controlled trial in patients who are in need for a peripherally inserted central catheter insertion in one teaching hospital in Belgium. The follow-up lasted 180 days or until catheter removal, whatever came first. A computer generated table was used to allocate devices. Randomised patients were 105 adults (StatLock, n=53; SecurAcath, n=52) and primary analysis was based on all patients (n=92) with time measurements (StatLock, n=43; SecurAcath, n=49)., Interventions: StatLock which has to be changed weekly versus SecurAcath which could remain in place for the complete catheter dwell time., Main Outcome Measure: Needed time for the dressing change at each dressing change (SecurAcath) or at each dressing change combined with the change of the securement device (StatLock)., Results: Median time needed for dressing change was 7.3 min (95% CI 6.4 min to 8.3 min) in the StatLock group and in the SecurAcath group 4.3 min (95% CI 3.8 min to 4.9 min) (P<0.0001). The time in the SecurAcath group was reduced with 41% (95% CI 29% to 51%). Incidence rates of migration, dislodgement and catheter-related bloodstream infection were comparable across groups. Pain scores were higher with SecurAcath than with StatLock at insertion (P=0.02) and at removal (P<0.001) and comparable during dressing change (P=0.38) and during dwell time (P=0.995). User-friendliness was scored at insertion and removal. All statements regarding the user-friendliness were scored significantly higher for StatLock than for SecurAcath (P<0.05). Only for the statement regarding the recommending routine use of the device, which was asked at removal, no difference was found between the two devices (P=0.32)., Conclusion: Use of SecurAcath saves time during dressing change compared with StatLock. Training on correct placement and removal of SecurAcath is critical to minimise pain., Trial Registration Number: NCT02311127; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Reward prediction errors (RPEs) are thought to drive learning. This has been established in procedural learning (e.g., classical and operant conditioning). However, empirical evidence on whether RPEs drive declarative learning-a quintessentially human form of learning-remains surprisingly absent. We therefore coupled RPEs to the acquisition of Dutch-Swahili word pairs in a declarative learning paradigm. Signed RPEs (SRPEs; "better-than-expected" signals) during declarative learning improved recognition in a follow-up test, with increasingly positive RPEs leading to better recognition. In addition, classic declarative memory mechanisms such as time-on-task failed to explain recognition performance. The beneficial effect of SRPEs on recognition was subsequently affirmed in a replication study with visual stimuli.

An outbreak of familial monkeypox occurred in the Central African Republic in 2015/2016 by 3 transmission modes: familial, health care-related, and transport-related. Ten people (3 children and 7 adults) were infected. Most presented with cutaneous lesions and fever, and 2 children died. The viral strain responsible was a Zaire genotype strain.

Optimally recruiting cognitive control is a key factor in efficient task performance. In line with influential cognitive control theories, earlier work assumed that control is relatively slow. We challenge this notion and test whether control also can be implemented more rapidly by investigating the time course of cognitive control. In two experiments, a visual discrimination paradigm was applied. A reward cue was presented with variable intervals to target onset. The results showed that reward cues can rapidly improve performance. Importantly, the reward manipulation was orthogonal to the response, ensuring that the reward effect was due to fast cognitive control implementation rather than to automatic activation of rewarded S-R associations. We also empirically specify the temporal limits of cognitive control, because the reward cue had no effect when it was presented shortly after target onset, during task execution.

We present the case of a 17-year-old boy, known with homozygous sickle cell disease, who was admitted because of generalised pain. He developed bilateral periorbital oedema and proptosis, without pain or visual disturbances. In addition to hyperhydration, oxygen and analgesia IV antibiotics were started, to cover a possible osteomyelitis. Patients with sickle cell disease are at risk for vaso-occlusive crises, when the abnormally shaped red blood cells aggregate and block the capillaries. Such a crisis typically presents at a location with high bone marrow activity, as the vertebrae and long bones. At an early age, the bone marrow is still active at other sites, for example the orbital wall, and thus infarction can also occur there. Thus, in young persons with sickle cell disease, it is important to consider orbital wall infarction in the differential diagnosis, since the approach is different from osteomyelitis. If the disease is complicated by an orbital compression syndrome, corticosteroids or surgical intervention may be necessary to preserve the vision. In our patient, an MRI of the orbitae demonstrated periorbital oedema with bone anomalies in the orbital and frontal bones, confirming orbital wall infarction. Ophthalmological examination revealed no signs of pressure on the nervus opticus. The patient recovered gradually with conservative treatment.

Objective: To investigate whether 57 genetic risk loci recently identified in a large-scale genome-wide association study in adult patients with multiple sclerosis (MS) are also associated with a risk for pediatric-onset MS and whether they can predict MS diagnosis in children presenting with acquired demyelinating syndromes (ADS)., Methods: We included 188 children with ADS, of whom 53 were diagnosed with MS, 466 patients with adult-onset MS, and 2,046 adult controls in our cohort study. Weighted genetic risk scores (wGRS) were calculated to evaluate genetic effects., Results: Mean wGRS was significantly higher for patients with pediatric-onset MS (7.32 ± 0.53) as compared with patients with monophasic ADS (7.10 ± 0.47, p = 0.01) and controls (7.11 ± 0.53, p < 0.01). We found no difference in mean wGRS of participants with monophasic ADS (7.10 ± 0.47) and controls (7.11 ± 0.53). The ability of the wGRS for the 57 single nucleotide polymorphisms (SNPs) to discriminate between children with MS and those with monophasic ADS was moderate (area under the curve [AUC] = 0.64), but improved with the addition of sex and HLA-DRB1*15 (AUC = 0.70). The combined effect of 57 SNPs exceeded the effect of HLA-DRB1*15 alone in our risk models for pediatric- and adult-onset MS., Conclusion: The previously reported 57 SNPs for adult-onset MS also confer increased susceptibility to pediatric-onset MS, but not to monophasic ADS.

Purpose/objectives: to investigate sensory perceptions of patients who underwent insertion of a totally implantable venous access device (TIVAD) under local anesthesia., Research Approach: qualitative, exploratory study., Setting: tertiary care center in Belgium., Participants: 20 adult patients with cancer or hematologic disease undergoing a first-time TIVAD insertion., Methodologic Approach: immediately after insertion, patients were asked to describe their sensory perceptions during each of four phases. Descriptions were documented in a sensory information grid (SIG) that was composed of a row and column matrix of entries for the four phases of the procedure and the five sensory modalities. Verbatim descriptions of patients were assigned labels using a descriptive coding process., Main Research Variables: sensory perceptions in the modalities of hearing, sight, touch, smell, and taste., Findings: patients experienced many sensory perceptions that mainly occurred during preparation of the patients and surgical equipment (phase 2) and during the actual TIVAD insertion (phase 3). Patients perceived fewer olfactory sensations. No taste perceptions were mentioned., Conclusions: patients reported numerous sensory perceptions during TIVAD insertion. The SIG method proved suitable for assessing and documenting patients' sensory perceptions., Interpretation: the reported descriptions can be used (a) to develop a structured questionnaire to quantitatively assess sensory perceptions and (b) to prepare patients for what to expect with regard to sensory information experienced before, during, and after TIVAD insertion. This method for exploring and documenting sensory perceptions might be applicable to other diagnostic or therapeutic interventions.

In a longitudinal experiment, effects of long-term tether housing on heart rate and behavioral responses to an acute stressor (a 15-min challenge with a nosesling) were investigated in pigs. The animals were challenged during loose housing and again after 10-11 weeks of tether housing. To detect possible changes in endogenous opioid systems modifying these responses, the pigs were pretreated with the opioid receptor antagonist naloxone (0.5 mg/kg body weight, iv). In response to the nosesling challenge, the animals showed pronounced resistance behavior and a sharp rise in heart rate. Following this initial phase of resistance, the heart rate dropped to prechallenge levels or below this line, and the pigs seemed to become sedated. Pretreatment with naloxone increased the heart rate response in animals that were long-term tether housed (n=12). No such effect was found in the control group (n=5) that was loose-housed during the entire experiment, indicating that the impact of endogenous opioid systems mitigating heart rate responses to acute stress had increased as a result of long-term tether housing. Changes in the effect of naloxone on the behavioral response were not found. Adaptive changes in opioid systems may prevent excessive physiological reactions to acute stress and, thus, may serve as a coping mechanism.

Effects of long-term tethered housing (a condition of chronic stress) on pituitary-adrenocortical responsiveness to exogenous corticotropin-releasing hormone (CRH) and lysine8-vasopressin (LVP) were investigated in female pigs. Intravenous administration of CRH (dose range 10-440 pmol/kg body wt) or LVP (10-880 pmol/kg body wt) elicited transient and dose-related increases in plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol. Comparison of the responses induced by the peptides indicated that CRH is a more potent ACTH secretagogue than LVP. Treatment with LVP produced a fivefold greater plasma cortisol/ACTH ratio than treatment with CRH, suggesting that in addition to stimulating pituitary ACTH release it enhanced the ability of the adrenal cortex to secrete cortisol in response to ACTH. Whereas concomitant administration of 10 pmol CRH/kg body wt and 20 pmol LVP/kg body wt revealed an additive effect on ACTH release, synergism between both peptides was found with respect to their cortisol-releasing effect. Ten to thirteen weeks of chronic stress did not alter significantly the absolute ACTH and cortisol responses to the two peptides. In tethered pigs, the cortisol/ACTH ratio after CRH treatment, calculated from the area under the curve, was twofold that in loose-housed pigs. From these observations we conclude that after chronic stress the sensitivity of the adrenocortex to circulating ACTH was increased, whereas the sensitivity of the pituitary to CRH and/or LVP remained unaltered.

The role of endogenous opioid mechanisms in the pituitary-adrenocortical response to acute stress was investigated in a longitudinal study in cyclic female pigs before and after exposure to chronic stress (long term tethered housing). Challenge of loose-housed pigs with acute nose-sling stress for 15 min induced an activation of the hypothalamic-pituitary-adrenocortical axis, evidenced by a transient increase in plasma ACTH (peak height above basal, 98 +/- 12 pg/ml; mean +/- SEM) and cortisol (54 +/- 3 ng/ml) concentrations. Pretreatment with the opioid receptor antagonist naloxone (0.5 mg/kg BW, iv bolus) increased the challenge-induced ACTH and cortisol responses to 244 +/- 36 pg/ml and 65 +/- 5 ng/ml, respectively. This indicates that during acute nose-sling stress, endogenous opioid systems are activated that inhibit the pituitary-adrenocortical response. After exposure of the pigs to chronic stress (10-11 weeks of tethered housing), the challenge-induced ACTH response was attenuated, whereas the cortisol response remained unchanged, suggesting an increased adrenocortical sensitivity to circulating ACTH. In addition, pretreatment with naloxone induced a greater increment in the ACTH and cortisol responses in tethered pigs than in loose-housed pigs. As no such changes were found in control animals housed loose during the entire experimental period, this indicates that the impact of opioid systems had increased due to chronic stress. The increased impact of opioid systems during chronic stress may prevent excessive hypothalamic-pituitary-adrenocortical responses to acute stressors and, thus, may be of adaptive value.

The influence of tethered housing (a condition of chronic stress) on morning and evening basal plasma cortisol levels was investigated in a longitudinal study in cyclic female nulliparous pigs (gilts). After a period of loose housing in individual pens ("nonstress" estrous cycles), six cannulated gilts were tethered by a neck chain and housed for a period of 20 wk (chronic stress estrous cycles). Blood was sampled twice daily (1000 and 1800 hr) for cortisol determination. Plasma cortisol levels showed a diurnal rhythm with significantly higher levels at 1000 hr than at 1800 hr. Tethered housing induced a significant increase in the 1800-hr plasma cortisol concentrations during the first three estrous cycles after tethering, whereas the 1000-hr plasma cortisol concentrations did not change throughout the experimental period. During the period of increased 1800-hr levels, cortisol was still released in a circadian fashion, albeit, the rhythm was flattened. In control gilts, housed loose during the entire experimental period, plasma cortisol concentrations at 1000 hr and at 1800 hr remained unaltered and 1000-hr cortisol concentrations were significantly higher than the 1800-hr concentrations during the experimental period. Therefore, possible effects of the experimental procedure or age-related effects could be excluded. These data indicate that, in tethered gilts, the chronic stress-induced hypercortisolemia is of transient nature, suggesting adaptive changes in the regulation of the hypothalamic-pituitary-adrenocortical axis. In addition, the data reveal circadian differences in the effect of chronic stress on hypothalamic-pituitary- adrenocortical function.

A method is presented to assess in vivo in transparent tissues the leukocyte subtypes that roll in microvessels. In nine rabbits anesthetized with ketamine-xylazine, leukocyte nuclei were stained in situ with acridine yellow (3 mg/kg i.v. for 5 min). Intravital fluorescence video microscopy in 24 mesenteric venules (17-29 microns, median 21) indicated labeling of all rolling leukocytes. On the basis of the shape of their nucleus, 67-100% (median 89) could be classified unequivocally (13-366 cells analyzed, median 77) as polymorphonuclear (PMN, i.e., granulocytes) or monomorphonuclear (lymphocytes and monocytes). Of these classified cells, 94-100% were PMNs (median 100, including 1 stray value of 69%). This PMN percentage was independent of the level of leukocyte rolling (2-36/min, median 14), vessel diameter, flow velocity (0.5-2.5 mm/s), or duration of the experiment (< 6 h). The dye had no significant influence on hemodynamic parameters, systemic leukocyte counts (1.5-7.8 x 10(9)/l), or in vitro differentiation pattern (27-38% granulocytes, 0-2% monocytes, 61-71% lymphocytes). In conclusion, our method demonstrated that the leukocytes that roll in postcapillary venules of the exteriorized rabbit mesentery are almost exclusively granulocytes.

In a longitudinal experiment, the influence of tethered housing (a condition of chronic stress) on the reactivity of the adrenal cortex to exogenous ACTH was investigated in gilts. To that end, the plasma cortisol response to synthetic ACTH (1-24; 10 micrograms/kg of BW; i.v. bolus injection via a permanent catheter) was determined before and after prolonged tethered housing. Two systems for tethered housing were used, one more restrictive than the other with regard to possibilities for visual and tactile contacts with conspecifics and visual control over the environment. The ACTH treatment induced a marked, transient plasma cortisol response in all gilts studied, irrespective of their housing conditions. Long-term tethered housing increased the ACTH-induced cortisol response. Possible effects of the experimental procedure or age-related effects could be excluded, because in control gilts, which were housed loose during the entire experimental period, the cortisol response to ACTH remained unaltered. The chronic stress-induced increase in the ACTH-induced cortisol response was considerably more pronounced and persistent in gilts that were deprived of possibilities for social contacts with conspecifics and visual control over the environment than in gilts with such possibilities. These data indicate that in tethered gilts adaptational changes occur at the level of the adrenal cortex that affect the ACTH-induced adrenocortical response. In addition, not only physical restraint but also restriction of social contact and visual control play an important role in the development of these changes.

Mutagen treatment of mouse P815 tumor cells produces immunogenic mutants that express new transplantation antigens (tum- antigens) recognized by cytolytic T cells. We found that the gene conferring expression of tum- antigen P91A contains 12 exons, encoding a 60 kd protein lacking a typical N-terminal signal sequence. The sequence shows no significant similarity with sequences in current data bases. A mutation that causes expression of the antigen is located in exon 4; it is the only apparent difference between the normal and the antigenic alleles. A short synthetic peptide corresponding to a region of exon 4 located around this mutation makes P815 cells sensitive to lysis by anti-P91A cytolytic T cells. The mutation creates a strong aggretope enabling the peptide to bind the H-2 Ld molecule. Several secondary tumor cell variants that no longer express tum- antigen P91A were found to carry deletions in the gene.