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The association between relational victimization and risk-taking development in children is understudied. Also, it is not clear how the social classroom norm may affect this link. The aim of this study was, therefore, to investigate the link between relational victimization and risk-taking behavior in elementary schoolchildren, and the potential moderating role of the classroom norm salience toward risk-taking. We expected that relationally victimized children would show an increase in risk-taking behavior in classrooms that are unfavorable toward risk-taking as a way to provoke and act against the classroom norm. However, alternatively, relationally victimized children could show an increase in risk-taking behavior in classrooms that are favorable toward risk-taking as a way to fortify the feeling of belonging to the classroom. Participants were 1,009 children (50% boys) in 69 classrooms of 13 mainstream elementary schools, followed annually across ages 7-11 (Grade 1-5). Risk-taking was assessed using the Balloon Analogue Risk Task. Relational victimization was assessed using teacher reports. The classroom norm salience toward risk-taking was based on the within-classroom correlation of risk-taking with children's social preference score among peers. Results from multilevel modeling showed that there was no significant main effect of relational victimization on risk-taking behavior. However, the classroom norm salience toward risk-taking significantly moderated the effect of relational victimization on risk-taking. Relational victimization was related to relative increases in risk-taking when classroom norms were unfavorable toward risk-taking. In classrooms where risk-taking was favored, relational victimization was related to relative decreases in risk-taking. These findings suggest that children who are relationally victimized may engage in norm-defying behavior in their classroom. Implications for further research are discussed.

Research has shown lower rates of employment and independent living in adults with autism. Many of these findings are based on cross-sectional studies, predominantly involving male participants. In a 6-year longitudinal study, we examined determinants of psychosocial outcomes in 917 adults with autism spectrum disorder (425 men, 492 women, mean age 43.5 years). Most were diagnosed in adulthood and had (above) average intellectual abilities. Via a yearly online survey, participants' objective psychosocial functioning (based on employment, independent living and friendship) and subjective well-being were assessed. Averaged across the five waves of the study, 86% of the sample showed a fair to very good level of objective psychosocial functioning. Objective psychosocial functioning and subjective well-being were positively correlated, and both improved over time. Lower intellectual ability, more autism traits, co-occurring psychiatric conditions and younger age predicted poorer objective outcomes. More autism traits and co-occurring psychiatric conditions predicted lower subjective well-being. There were no gender differences in initial levels of, or changes in, objective and subjective outcomes over time. This study has identified important risk/protective factors for psychosocial outcomes across early and middle adulthood. In general, the findings offer a more positive outlook for adults with autism and average to high intellectual abilities.

Background: Addressing socioeconomic inequalities in early child development (ECD) is key to reducing the intergenerational transmission of health inequalities. Yet, little is known about how socioeconomic inequalities in ECD develop over the course of childhood. Our study aimed to describe how inequalities in ECD by maternal education develop from infancy to middle childhood. Methods: We used data from Generation R, a prospective population-based cohort study in The Netherlands. Language skills were measured at ages 1, 1.5, 2, 3, and 4 years, using the Minnesota Child Development Inventory. Socioemotional (i.e. internalizing and externalizing) problems were measured at ages 1.5, 3, 5 and 9 years using the Child Behavior Checklist. We estimated inequalities in language skills and socioemotional problems across the above-mentioned ages, using linear mixed models with standardized scores at each wave. We used maternal education as indicator of socioeconomic position. Results: Children of less educated mothers had more reported internalizing (B = 0.72, 95%CI = 0.51;0.95) and externalizing (B = 0.25, 95%CI = 0.10;0.40) problems at age 1.5 years, but better (caregiver reported) language skills at 1 year (B = 0.50, 95%CI = 0.36;0.64) than children of high educated mothers. Inequalities in internalizing and externalizing problems decreased over time. Inequalities in language scores reversed at age 2, and by the time children were 4 years old, children of less educated mothers had substantially lower language skills than children of high educated mothers (B = -0.38, 95%CI = -0.61;-0.15). Conclusions: Trajectories of socioeconomic inequality in ECD differ by developmental domain: whereas inequalities in socioemotional development decreased over time, inequalities increased for language development. Children of less educated mothers are at a language disadvantage even before entering primary education, providing further evidence that early interventions are needed. [ABSTRACT FROM AUTHOR]

We investigated the prevalence of azole resistance of Aspergillus fumigatus isolates in the Netherlands by screening clinical A. fumigatus isolates for azole resistance during 2013-2018. We analyzed azole-resistant isolates phenotypically by in vitro susceptibility testing and for the presence of resistance mutations in the Cyp51A gene. Over the 6-year period, 508 (11%) of 4,496 culture-positive patients harbored an azole-resistant isolate. Resistance frequency increased from 7.6% (95% CI 5.9%-9.8%) in 2013 (58/760 patients) to 14.7% (95% CI 12.3%-17.4%) in 2018 (112/764 patients) (p = 0.0001). TR34/L98H (69%) and TR46/Y121F/T289A (17%) accounted for 86% of Cyp51A mutations. However, the mean voriconazole MIC of TR34/L98H isolates decreased from 8 mg/L (2013) to 2 mg/L (2018), and the voriconazole-resistance frequency was 34% lower in 2018 than in 2013 (p = 0.0001). Our survey showed changing azole phenotypes in TR34/L98H isolates, which hampers the use of current PCR-based resistance tests. [ABSTRACT FROM AUTHOR]

Summary: Background: Fungal diseases have an ever‐increasing global disease burden, although regional estimates for specific fungal diseases are often unavailable or dispersed. Objectives: Here, we report the current annual burden of life‐threatening and debilitating fungal diseases in the Netherlands. Methods: The most recent available epidemiological data, reported incidence and prevalence of fungal diseases were used for calculations. Results: Overall, we estimate that the annual burden of serious invasive fungal infections in the Netherlands totals 3 185 patients, including extrapulmonary or disseminated cryptococcosis (n = 9), pneumocystis pneumonia (n = 740), invasive aspergillosis (n = 1 283), chronic pulmonary aspergillosis (n = 257), invasive Candida infections (n = 684), mucormycosis (n = 15) and Fusarium keratitis (n = 8). Adding the prevalence of recurrent vulvo‐vaginal candidiasis (n = 220 043), allergic bronchopulmonary aspergillosis (n = 13 568) and severe asthma with fungal sensitisation (n = 17 695), the total debilitating burden of fungal disease in the Netherlands is 254 491 patients yearly, approximately 1.5% of the country's population. Conclusion: We estimated the annual burden of serious fungal infections in the Netherlands at 1.5% of the population based on previously reported modelling of fungal rates for specific populations at risk. With emerging new risk groups and increasing reports on antifungal resistance, surveillance programmes are warranted to obtain more accurate estimates of fungal disease epidemiology and associated morbidity and mortality. [ABSTRACT FROM AUTHOR]

Adults are 38% more likely to suffer from a psychiatric disorder when they live in an urban compared to a rural area. Urban upbringing may be particularly important. The aim of the present study was to examine whether urbanicity was independently associated with mental health in elementary school-aged children. Specifically, we investigated whether living in a more urban area was associated with exhibiting more behavioral and emotional problems, and whether this remained while controlling for other major risk factors for mental health problems in children. Data came from a Dutch general population study of children (n = 895). Information from four waves was used, in which children were aged approximately 8, 9, 11, and 12 years old. We used mixed effects models to assess the association between urbanicity and the outcomes of behavioral problems and emotional problems separately, while controlling for other major risk factors. The analyses showed that children who lived in more urban areas were significantly more likely to exhibit behavioral (p < .001) and emotional (p < .001) problems. This effect remained when controlling for neighborhood socioeconomic status, gender, ethnicity, family socioeconomic status, parental symptoms of psychopathology, parenting stress, and parenting practices (behavioral: p = .02, emotional: p = .009). In line with research in adults, urbanicity seems to be independently associated with behavioral and emotional problems in children. A possible underlying mechanism is that the city is a stressful environment for children to grow up in, which contributes to an increased risk for mental health problems. [ABSTRACT FROM AUTHOR]

Introduction Palbociclib is a cyclin dependent kinase (CDK) 4/6 inhibitor with nanomolar potency and was recently approved for treatment of breast cancer. The drug may also be useful in glioblastoma (GBM) and diffuse intrinsic pontine gliomas (DIPG), which often have an activated CDK4/6-retinoblastoma signaling pathway. However, GBM and DIPG spread widely into the surrounding brain, which calls for a CDK4/6 inhibitor with sufficient blood-brain barrier penetration. Methods We first performed in vitro transwell assays and demonstrate that palbociclib is a substrate of both P-gp and BCRP. Next, we conducted pharmacokinetic studies using wildtype, Abcg2, Abcb1a/b and Abcg2; Abcb1a/b mice. Results The plasma levels were about 3000 and 500 nM and similar in all genotypes at 1 and 4 h after i.v. administration of 10 mg/kg. At 4 h the brain-to-plasma ratios were 0.3 in WT and Abcg2 mice versus 5.5 and 15 in Abcb1a/b and Abcg2; Abcb1a/b mice, respectively. The oral bioavailability of palbociclib was high (63 %) in WT mice and increased only modestly and non-significantly in Abcg2; Abcb1a/b mice. The plasma level after oral dosing of 150 mg/kg was already much higher than observed in patients (200-400 nM) and exceeded 2500 nM for up to 24 h. This latter dose is commonly used in preclinical studies, which calls into question their predictive value as they were conducted at dose levels causing a clinically non-relevant systemic drug exposure. Conclusion Thus, the brain penetration of palbociclib is restricted by P-gp and BCRP, which may restrict the efficacy against GBM and DIPG. Moreover, preclinical studies with this agent should be conducted at a more clinically relevant dose level. [ABSTRACT FROM AUTHOR]

Otomastoiditis caused by the anaerobic Fusobacterium necrophorum (F. necrophorum) often induces severe complications, such as meningitis and sinus thrombosis. Early diagnosis is difficult, partly because little is known about specific early signs. Comprehensive research about clinically chosen antimicrobial therapy has not been done yet and prognostic information about otomastoiditis caused by F. necrophorum is scarce. More knowledge about this subject is required. In this retrospective cohort study, we included all cases of otomastoiditis caused by F. necrophorum treated in two university medical centres in the Netherlands during the past 10 years. Data was gathered from patient records and analysed using independent sample T-tests and Chi2-tests. This study reveals that otomastoiditis caused by F. necrophorum potentially induces neurological sequelae. Thereby, 80% of all included patients (n = 16) needed readmission within six months due to recurrence or complications of otomastoiditis caused by F. necrophorum. Mean (range) of age, CRP and temperature were 4.5 years (0.9–29.3), 243 mg/L (113–423) and 40 °C (37–41). All patients were hospitalized and treated with antibiotics, mostly metronidazole (n = 13/16) and a β -lactam (n = 15/16). Additional treatment contained low molecular weight heparin (83%, n = 10/12), dexamethasone (78%, n = 7/9) and/or surgery (80%, n = 12/16, whereof 9/12 mastoidectomy). Patients and/or their parents need to be informed about this potential unfortunate prognosis when otomastoiditis caused by F. necrophorum is diagnosed. To improve early diagnosis, otomastoiditis caused by F. necrophorum should be suspected and therefore immediately cultured when a) young children present with otomastoiditis, with b) high CRP values, and/or c) vomiting and decreased consciousness. ∙Otomastoiditis caused by F. necrophorum can induce neurological sequelae. ∙ Readmission is often needed due to recurrence/complications of the disease. ∙Patients(' parents) need to be informed about its potential unfortunate prognosis. ∙Patients are often of young age and show severe clinical presentation. ∙Antibiotics are leading in treatment, potential combined with mastoidectomy. [ABSTRACT FROM AUTHOR]