Merel van der Meulen

To examine whether bullying is strategic behavior aimed at obtaining or maintaining social dominance, 1129 9- to 12-year-old Dutch children were classified in terms of their role in bullying and in terms of their use of dominance oriented coercive and prosocial social strategies. Multi-informant measures of participants' acquired and desired social dominance were also included. Unlike non-bullying children, children contributing to bullying often were bistrategics in that they used both coercive and prosocial strategies and they also were socially dominant. Ringleader bullies also expressed a higher desire to be dominant. Among non-bullying children, those who tended to help victims were relatively socially dominant but victims and outsiders were not. Generally, the data supported the claim that bullying is dominance-oriented strategic behavior, which suggests that intervention strategies are more likely to be successful when they take the functional aspects of bullying behavior into account.

Researchers typically employ either peer or self-reports to assess involvement in bullying. In this study, we examined the merits of each method for the identification of child characteristics related to victimization and bullying others. Accordingly, we investigated the difference between these two methods with regard to their relationship with social adjustment (i.e., perceived popularity, likeability, and self-perceived social acceptance) and internalizing problems (i.e., anxiety, depression, and self-worth) in 1192 Dutch school children, aged 9 to 12 years. Perceived popularity and likeability were more strongly correlated with peer reports than self-reports, for both victimization and for bullying others. Self-perceived social acceptance correlated equally strong with peer and self- reports of victimization. Furthermore, peer reports of bullying were also correlated with self-perceived social acceptance, whereas self-reports of bullying were not. All internalizing problems showed stronger relations with self-reports than peer reports; although only the relation between self-reported victimization and internalizing problems was of practical significance. Despite our findings indicating that using only one type of report could be efficient for examining the relation between bullying behaviors and separate child characteristics, both types of report are necessary for a complete understanding of the personal and social well-being of the children involved.

Bullying is increasingly conceptualized as strategic behavior motivated by a desire to gain social dominance in the peer group. Cross-sectional research has shown that relative to their peers bullies are higher in social dominance as indexed by resource control, and are often perceived as powerful and “cool.” However, research examining the developmental relationship between bullying and resource control is lacking. The present longitudinal study fills this gap in the literature. Using a three wave design, participants (N = 394) were followed from late childhood into early adolescence. Joint trajectory analyses were used to test whether groups with distinct developmental trajectories of bullying and resource control can be identified, and how these trajectories are related. For both bullying and resource control three groups emerged (high, medium, and low), indicating that bullies and social dominants do not constitute one homogeneous group. More intense bullying is associated with higher levels of social dominance. Being consistently high in bullying is almost synonymous with being consistently high in resource control, whereas the reverse is not the case. Findings suggest that high bullying leads to the attainment of high social dominance, and do not support the view that children high in social dominance engage in bullying to maintain their dominant position. This study further underscores the need for interventions targeting mechanisms by which the peer group assigns social dominance to bullies.

The extent to which people implement government-issued protective measures is critical in preventing further spread of coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2. Our study aimed to describe the public belief in the effectiveness of protective measures, the reported implementation of these measures, and to identify communication channels used to acquire information on COVID-19 in European countries during the early stage of the pandemic.An online survey available in multiple languages was disseminated starting on March 19th, 2020. After five days, we computed descriptive statistics for countries with more than 500 respondents. Each day, we assessed enacted community containment measures by stage of stringency (I-IV). In total, 9,796 adults responded, of whom 8,611 resided in the Netherlands (stage III), 604 in Germany (stage III), and 581 in Italy (stage IV). To explore possible dynamics as containment strategies intensified, we also included 1,365 responses submitted during the following week. Participants indicated support for governmental measures related to avoiding social gatherings, selective closure of public places, and hand hygiene and respiratory measures (range for all measures: 95.0%-99.7%). Respondents from the Netherlands less frequently considered a complete social lockdown effective (59.2%), compared to respondents in Germany (76.6%) or Italy (87.2%). Italian residents applied enforced social distancing measures more frequently (range: 90.2%-99.3%, German and Dutch residents: 67.5%-97.0%) and self-initiated hygienic and social distancing behaviors (range: 36.3%-96.6%, German and Dutch residents: 28.3%-95.7%). Respondents reported being sufficiently informed about the outbreak and behaviors to avoid infection (range: 90.2%-91.1%). Information channels most commonly reported included television newspapers, official health websites, and social media. One week later, we observed no major differences in submitted responses.During the early stage of the COVID-19 pandemic, belief in the effectiveness of protective measures among survey respondents from three European countries was high and participants reported feeling sufficiently informed. In March 2020, implementation of measures differed between countries and were highest among respondents from Italy, who were subjected to the most stringent lockdown measures and greatest COVID-19 burden in Europe during this period.

A few previous studies have shown that narcissistic traits in youth are positively associated with bullying. However, research examining the developmental relationship between narcissism and bullying is lacking. Moreover, it is unclear whether narcissists constitute a homogeneous group and whether the bullying of narcissistic youth results in establishing social dominance over peers. The present work addresses these gaps. Children (N = 393; M age = 10.3; 51 % girls) were followed during the last 3 years of primary school. Person-centered analyses were used to examine whether groups with distinct developmental trajectories for narcissism and two bullying forms (direct and indirect) can be identified, and how these trajectories are related. Multiple groups emerged for all constructs examined. For girls, higher narcissism was neither related to more intense bullying, nor to higher social dominance. In contrast, highly narcissistic boys were more likely than their peers to show elevated direct bullying, and in particular elevated indirect bullying. Hence, high narcissism is a risk factor for bullying in boys, but not in girls. However, narcissism is not always accompanied by high bullying, given that many boys on the high bullying trajectories were not high in narcissism. Results show that among narcissistic youth only those who engage in high levels of bullying are high in social dominance.

To reduce bullying, more knowledge on children defending their victimized peers is critical. In previous work, predominantly cross‐sectional in nature, defending has typically been operationalized as one single, broad construct. However, there are good reasons to assume that attacking the bully (bully oriented defending) and comforting the victim (victim‐oriented defending) are relatively independent constructs, with potentially different correlates. This longitudinal study in the Netherlands ( N = 394; M age = 10.3) combined person‐ and variable‐centered techniques to examine relations between two different forms of defending and multiple outcome variables. In addition to the largest group scoring low on both types of defending, three subgroups emerged. A small group of “traditional,” predominantly female defenders, scored high on both forms of defending. These children were well liked and high in reputation‐based status, as indexed by perceived popularity and resource control. A larger, predominantly female second group only scored high on victim‐oriented defending. These children were also well liked, but low in reputation‐based status. The third group only scored high on bully oriented defending, and predominantly contained boys. These children were high in reputation‐based status but quite disliked, and they scored high on bullying. Findings strongly suggest that bully oriented defending does not in all cases reflect desirable interventions of empathic children. Aggr. Behav. 42:585–597, 2016. © 2016 Wiley Periodicals, Inc.

Abstract The metabolic and cardiovascular clinical manifestations in patients with Cushing's syndrome (CS) are generally well known. However, recent studies have broadened the perspective of the effects of hypercortisolism, showing that both endogenous and exogenous glucocorticoid excess alter brain functioning on several time scales. Consequently, cognitive deficits and neuropsychological symptoms are highly prevalent during both active CS and CS in remission, as well as during glucocorticoid treatment. In this review, we discuss the effects of endogenous hypercortisolism and exogenously induced glucocorticoid excess on the brain, as well as the prevalence of cognitive and neuropsychological deficits and their course after biochemical remission. Furthermore, we propose possible mechanisms that may underly neuronal changes, based on experimental models and in vitro studies. Finally, we offer recommendations for future studies.

Objective To test the hypothesis that systemic and inhaled glucocorticoid use is associated with changes in grey matter volume (GMV) and white matter microstructure. Design Cross-sectional study. Setting UK Biobank, a prospective population-based cohort study of adults recruited in the UK between 2006 and 2010. Participants After exclusion based on neurological, psychiatric or endocrinological history, and use of psychotropic medication, 222 systemic glucocorticoid users, 557 inhaled glucocorticoid users and 24 106 controls with available T1 and diffusion MRI data were included. Main outcome measures Primary outcomes were differences in 22 volumetric and 14 diffusion imaging parameters between glucocorticoid users and controls, determined using linear regression analyses adjusted for potential confounders. Secondary outcomes included cognitive functioning (six tests) and emotional symptoms (four questions). Results Both systemic and inhaled glucocorticoid use were associated with reduced white matter integrity (lower fractional anisotropy (FA) and higher mean diffusivity (MD)) compared with controls, with larger effect sizes in systemic users (FA: adjusted mean difference (AMD)=−3.7e-3, 95% CI=−6.4e-3 to 1.0e-3; MD: AMD=7.2e-6, 95% CI=3.2e-6 to 1.1e-5) than inhaled users (FA: AMD=−2.3e-3, 95% CI=−4.0e-3 to −5.7e-4; MD: AMD=2.7e-6, 95% CI=1.7e-7 to 5.2e-6). Systemic use was also associated with larger caudate GMV (AMD=178.7 mm 3 , 95% CI=82.2 to 275.0), while inhaled users had smaller amygdala GMV (AMD=−23.9 mm 3 , 95% CI=−41.5 to −6.2) than controls. As for secondary outcomes, systemic users performed worse on the symbol digit substitution task (AMD=−0.17 SD, 95% CI=−0.34 to −0.01), and reported more depressive symptoms (OR=1.76, 95% CI=1.25 to 2.43), disinterest (OR=1.84, 95% CI=1.29 to 2.56), tenseness/restlessness (OR=1.78, 95% CI=1.29 to 2.41), and tiredness/lethargy (OR=1.90, 95% CI=1.45 to 2.50) compared with controls. Inhaled users only reported more tiredness/lethargy (OR=1.35, 95% CI=1.14 to 1.60). Conclusions Both systemic and inhaled glucocorticoid use are associated with decreased white matter integrity and limited changes in GMV. This association may contribute to the neuropsychiatric side effects of glucocorticoid medication, especially with chronic use.

The European Reference Network on Rare Endocrine Conditions (Endo-ERN) aims to organize high-quality healthcare throughout Europe, including care for pituitary adenoma patients. As surgery is the mainstay of treatment, we aimed to describe the current surgical practice and published surgical outcomes of pituitary adenoma within Endo-ERN.Systematic review and meta-analysis of studies reporting surgical outcomes of pituitary adenoma patients within Endo-ERN MTG6 pituitary reference centers between 2010 and 2019. A survey was completed by reference centers on their current surgical practice.A total of 18 out of 43 (42%) reference centers located in 7 of the 20 (35%) MTG6-represented countries published 48 articles. Remission rates were 50% (95% CI: 42-59) for patients with acromegaly, 68% (95% CI: 60-75) for Cushing's disease, and 53% (95% CI: 39-66%) for prolactinoma. Gross total resection was achieved in 49% (95% CI: 37-61%) of patients and visual improvement in 78% (95% CI: 68-87). Mortality, hemorrhage, and carotid injury occurred in less than 1% of patients. New-onset hypopituitarism occurred in 16% (95% CI: 11-23), transient diabetes insipidus in 12% (95% CI: 6-21), permanent diabetes insipidus in 4% (95% CI: 3-6), syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in 9% (95% CI: 5-14), severe epistaxis in 2% (95% CI: 0-4), and cerebrospinal fluid leak in 4% (95% CI: 2-6). Thirty-five (81%) centers completed the survey: 54% were operated endoscopically and 57% were together with an ENT surgeon.The results of this study could be used as a first benchmark for the outcomes of pituitary adenoma surgery within Endo-ERN. However, the heterogeneity between studies in the reporting of outcomes hampers comparability and warrants outcome collection through registries.

Glucocorticoids are powerful modulators of brain function. They act via mineralocorticoid and glucocorticoid receptors (MR and GR). These are best understood as transcription factors. Although many glucocorticoid effects depend on the modulation of gene transcription, it is a major challenge to link gene expression to function given the large-scale, apparently pleiotropic genomic responses. The extensive sets of MR and GR target genes are highly specific per cell type, and the brain contains many different (neuronal and non-neuronal) cell types. Next to the set "trait" of cellular context, the "state" of other active signaling pathways will affect MR and GR transcriptional activity. Here, we discuss receptor specificity and contextual factors that determine the transcriptional outcome of MR/GR signaling, experimental possibilities offered by single-cell transcriptomics approaches, and reflect on how to make sense of lists of target genes in relation to understanding the functional effects of steroid receptor activation.

Abstract Hawley's influential resource control theory (RCT) posits that both coercive and prosocial strategies may yield social dominance, as indexed by resource control. Based on differences in youths’ relative use of these strategies, RCT a priori defines five distinct subtypes. Several studies by Hawley and colleagues have revealed substantial differences between subtypes in terms of obtained resource control and various social characteristics (e.g., agreeableness). The present longitudinal study (N = 394; M age = 10.3; SD = 0.5) expands on previous work. Firstly, because several items used to assess strategies in RCT appear to confound strategy use with the resulting benefits (resource control), we disentangled between strategy use as such and obtained resource control. Secondly whereas previous work has been exclusively cross‐sectional, the present study was longitudinal. ANOVAs comparing subgroups provided support for some core tenets of RCT, but not for others. For instance, bistrategic children scored high on both resource control and perceived popularity. However, bistrategics engaged in elevated bullying, and whereas Hawley asserts that they are proficient in balancing ‘getting ahead’ with ‘getting along’, their behavior appeared to evoke clear negative reactions in the peer group at large. Findings also showed that non‐controllers did not experience more negative outcomes than their peers across all domains.

In most patients with pituitary adenomas magnetic resonance imaging (MRI) is essential to guide effective decision-making. T1- and T2-weighted sequences allow the majority of adenomas to be readily identified. Supplementary MR sequences (e.g. FLAIR; MR angiography) may also help inform surgery. However, in some patients MRI findings are ‘negative’ or equivocal (e.g. with failure to reliably identify a microadenoma or to distinguish postoperative change from residual/recurrent disease). Molecular imaging [e.g. 11 C-methionine PET/CT coregistered with volumetric MRI (Met-PET/MR CR )] may allow accurate localisation of the site of de novo or persistent disease to guide definitive treatment (e.g. surgery or radiosurgery).

During adolescence, youth become more likely to avoid involvement in witnessed bullying and less likely to support victims. It is unknown whether—and how—these bystander behaviors (i.e., outsider behavior and indirect defending) are associated with adolescents' peer‐group status (i.e., popularity and social acceptance) over time. Cross‐lagged path modeling was used to examine these longitudinal associations in a sample of 313 Dutch adolescents ( M age‐T1 = 10.3 years). The results showed that status longitudinally predicted behavior, rather than that behavior predicted status. Specifically, unpopularity predicted outsider behavior and social acceptance predicted indirect defending. These findings suggest that a positive peer‐group status can trigger adolescents' provictim stance. However, adolescents may also strategically avoid involvement in witnessed bullying to keep a low social profile.

Abstract Background Pituitary adenomas can give rise to a variety of clinical disorders and surgery is often the primary treatment option. However, preoperative magnetic resonance imaging (MRI) does not always reliably identify the site of an adenoma. In this setting molecular (functional) imaging (e.g. 11 C-methionine PET/CT) may help with tumor localisation, although interpretation of these 2D images can be challenging. 3D printing of anatomical models for other indications has been shown to aid surgical planning and improve patient understanding of the planned procedure. Here, we explore the potential utility of four types of 3D printing using PET/CT and co-registered MRI for visualising pituitary adenomas. Methods A 3D patient-specific model based on a challenging clinical case was created by segmenting the pituitary gland, pituitary adenoma, carotid arteries and bone using contemporary PET/CT and MR images. The 3D anatomical models were printed using VP, MEX, MJ and PBF 3D printing methods. Different anatomical structures were printed in color with the exception of the PBF anatomical model where a single color was used. The anatomical models were compared against the computer model to assess printing accuracy. Three groups of clinicians (endocrinologists, neurosurgeons and ENT surgeons) assessed the anatomical models for their potential clinical utility. Results All of the printing techniques produced anatomical models which were spatially accurate, with the commercial printing techniques (MJ and PBF) and the consumer printing techniques (VP and MEX) demonstrating comparable findings (all techniques had mean spatial differences from the computer model of < 0.6 mm). The MJ, VP and MEX printing techniques yielded multicolored anatomical models, which the clinicians unanimously agreed would be preferable to use when talking to a patient; in contrast, 50%, 40% and 0% of endocrinologists, neurosurgeons and ENT surgeons respectively would consider using the PBF model. Conclusion 3D anatomical models of pituitary tumors were successfully created from PET/CT and MRI using four different 3D printing techniques. However, the expert reviewers unanimously preferred the multicolor prints. Importantly, the consumer printers performed comparably to the commercial MJ printing technique, opening the possibility that these methods can be adopted into routine clinical practice with only a modest investment.

To assess the potential for 11C-methionine PET (Met-PET) coregistered with volumetric magnetic resonance imaging (Met-PET/MRCR) to inform clinical decision making in patients with poorly visualized or occult microprolactinomas and dopamine agonist intolerance or resistance.Thirteen patients with pituitary microprolactinomas, and who were intolerant (n = 11) or resistant (n = 2) to dopamine agonist therapy, were referred to our specialist pituitary centre for Met-PET/MRCR between 2016 and 2020. All patients had persistent hyperprolactinemia and were being considered for surgical intervention, but standard clinical MRI had shown either no visible adenoma or equivocal appearances.In all 13 patients Met-PET/MRCR demonstrated a single focus of avid tracer uptake. This was localized either to the right or left side of the sella in 12 subjects. In one patient, who had previously undergone surgery for a left-sided adenoma, recurrent tumor was unexpectedly identified in the left cavernous sinus. Five patients underwent endoscopic transsphenoidal selective adenomectomy, with subsequent complete remission of hyperprolactinaemia and normalization of other pituitary function; three patients are awaiting surgery. In the patient with inoperable cavernous sinus disease PET-guided stereotactic radiosurgery (SRS) was performed with subsequent near-normalization of serum prolactin. Two patients elected for a further trial of medical therapy, while two declined surgery or radiotherapy and chose to remain off medical treatment.In patients with dopamine agonist intolerance or resistance, and indeterminate pituitary MRI, molecular (functional) imaging with Met-PET/MRCR can allow precise localization of a microprolactinoma to facilitate selective surgical adenomectomy or SRS.

Synthetic glucocorticoids are widely used among patients suffering from a wide range of diseases. Glucocorticoids are very efficacious, but can be accompanied by neuropsychiatric adverse effects. This systematic review and meta-analysis assesses and quantifies the proportion of different neuropsychiatric adverse effects in patients using synthetic glucocorticoids.Six electronic databases were searched to identify potentially relevant studies. Randomized controlled trials, cohort and cross-sectional studies assessing psychiatric side effects of glucocorticoids measured with validated questionnaires were eligible. Risk of bias was assessed with RoB 2, ROBINS-I, and AXIS appraisal tool. For proportions of neuropsychiatric outcomes, we pooled proportions, and when possible, differences in questionnaire scores between glucocorticoid users and non-users were expressed as standardized mean differences (SMD). Data were pooled in a random-effects logistic regression model.We included 49 studies with heterogeneity in study populations, type, dose, and duration of glucocorticoids. For glucocorticoid users, meta-analysis showed a proportion of 22% for depression (95%CI 14%-33%), 11% for mania (95%CI 2%-46%), 8% for anxiety (95%CI 2%-25%), 16% for delirium (95%CI 6%-36%), and 52% for behavioural changes (95%CI 42%-61%). Questionnaire scores for depression (SMD of 0.80 (95%CI 0.35-1.26)), and mania (0.78 (95%CI 0.14-1.42)) were higher than in controls, indicating more depressive and manic symptoms following glucocorticoid use.The heterogeneity of glucocorticoid use is reflected in the available studies. Despite this heterogeneity, the proportion of neuropsychiatric adverse effects in glucocorticoid users is high. The most substantial associations with glucocorticoid use were found for depression and mania. Upon starting glucocorticoid treatment, awareness of possible psychiatric side effects is essential. More structured studies on incidence and potential pathways of neuropsychiatric side effects of prescribed glucocorticoids are clearly needed.

Pituitary adenomas (PA) affect ~ 1:1200 of the population and can cause a wide range of symptoms due to hormone over-secretion, loss of normal pituitary gland function and/or compression of visual pathways, resulting in significantly impaired quality of life. Surgery is potentially curative if the location of the adenoma can be determined. However, standard structural (anatomical) imaging, in the form of MRI, is unable to locate all tumors, especially microadenomas (< 1 cm diameter). In such cases, functional imaging [11C-methionine PET/CT (Met-PET)] can facilitate tumor detection, although may be inconclusive when the adenoma is less metabolically active. We, therefore, explored whether subtraction imaging, comparing findings between two Met-PET scans with medical therapy-induced suppression of tumor activity in the intervening period, could increase confidence in adenoma localization. In addition, we assessed whether normalization to a reference region improved consistency of pituitary gland signal in healthy volunteers who underwent two Met-PET scans without medical suppression.We found that the mean percentage differences in maximum pituitary uptake between two Met-PET scans in healthy volunteers were 2.4% for (SUVr) [cerebellum], 8.8% for SUVr [pons], 5.2% for SUVr [gray matter] and 23.1% for the SUVbw [no region]. Laterality, as measured by contrast-noise ratio (CNR), indicated the correct location of the adenoma in all three image types with mean CNR values of 6.2, 8.1 and 11.1 for SUVbw, SUVbwSub and SUVrSub [cerebellum], respectively. Subtraction imaging improved CNR in 60% and 100% of patients when using images generated from SUVbw [no region] and SUVr [cerebellum] scans compared to standard clinical SUVbw imaging.Met-PET scans should be normalized to the cerebellum to minimize the effects of physiological variation in pituitary gland uptake of 11C-methionine, especially when comparing serial imaging. Subtraction imaging following endocrine suppression of tumor function improved lateralization of PA when compared with single time point clinical Met-PET but, importantly, only if the images were normalized to the cerebellum prior to subtraction.

Successful immunization often requires a primer, and after a certain lag time, a booster administration of the antigen. To improve the vaccinees’ comfort and compliance, a single-injection vaccine formulation with a biphasic pulsatile release would be preferable. Previous work has shown that such a release profile can be obtained with compacts prepared from physical mixtures of various poly(dl-lactic(-co-glycolic) acid) types (Murakami et al., 2000). However, the mechanism behind this release profile is not fully understood. In the present study, the mechanism that leads to this biphasic pulsatile release was investigated by studying the effect of the glass transition temperature (Tg) of the polymer, the temperature of compaction, the compression force, the temperature of the release medium, and the molecular weight of the incorporated drug on the release behavior. Compaction resulted in a porous compact. Once immersed into release medium with a temperature above the Tg of the polymer, the drug was released by diffusion through the pores. Simultaneously, the polymer underwent a transition from the glassy state into the rubbery state. The pores were gradually closed by viscous flow of the polymer and further release was inhibited. After a certain period of time, the polymer matrix ruptured, possibly due to a build-up in osmotic pressure, resulting in a pulsatile release of the remaining amount of drug. The compression force and the molecular weight of the incorporated drug did not influence the release profile. Understanding this mechanism could contribute to further develop single-injection vaccines.

Using data from 2413 Dutch first-year secondary school students (M age=13.27, SD age=0.51, 49.0% boys), this study investigated as to what extent students who according to their self-reports had not been victimized (referred to as reporters) gave victimization nominations to classmates who according to their self-reports had been victimized (referred to as receivers). Using a dyadic approach, characteristics of the reporter-receiver dyad (i.e., gender similarity) and of the reporter (i.e., reporters' behavior during bullying episodes) that were possibly associated with reporter-receiver agreement were investigated. Descriptive analyses suggested that numerous students who were self-reported victims were not perceived as victimized by their non-victimized classmates. Three-level logistic regression models (reporter-receiver dyads nested in reporters within classrooms) demonstrated greater reporter-receiver agreement in same-gender dyads, especially when the reporter and the receiver were boys. Furthermore, reporters who behaved as outsiders during bullying episodes (i.e., reporters who actively shied away from the bullying) were less likely to agree on the receiver's self-reported victimization, and in contrast, reporters who behaved as defenders (i.e., reporters who helped and supported victims) were more likely to agree on the victimization. Moreover, the results demonstrated that reporters gave fewer victimization nominations to receivers who reported they had been victimized sometimes than to receivers who reported they had been victimized often/very often. Finally, this study suggested that reporter-receiver agreement may not only depend on characteristics of the reporter-receiver dyad and of the reporter, but on classroom characteristics as well (e.g., the number of students in the classroom).

ABSTRACT Objectives The extent to which people implement government-issued protective measures is critical in preventing further spread of coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2. Our study aimed to evaluate the public belief in the effectiveness of protective measures, the reported implementation of these measures in daily life, and to identify communication channels used to acquire relevant information on COVID-19 in European countries. Design A cross-sectional online survey available in multiple languages was disseminated on social media starting March 19th, 2020. After five days, we computed descriptive statistics for countries with more than 500 respondents. Each day, we compiled and categorized community containment measures enacted in each country by stringency (stage I-IV). Response collection continued for one week to explore possible dynamics as containment strategies intensified. Participants In total, 9,796 adults responded, of whom 8,611 resided in the Netherlands (stage III), 604 in Germany (stage III), and 581 in Italy (stage IV). An additional 1,365 respondents completed the survey in the following week. Results Participants indicated support for governmental measures related to avoiding social gatherings, selective closure of public places, and hand hygiene and respiratory measures (range for all measures: 95.0%-99.7%). Respondents from the Netherlands were less likely to consider a complete social lockdown effective (59.2%), compared to respondents in Germany (76.6%) or Italy (87.2%). Italian residents did not only apply enforced social distancing measures more frequently (range: 90.2%-99.3%, German and Dutch residents: 67.5%-97.0%), but also self-initiated hygienic and social distancing behaviors (range: 36.3%-96.6%, German and Dutch residents: 28.3%-95.7%). Respondents largely reported being sufficiently informed about the COVID-19 outbreak and about behaviors to avoid infection (range across countries: 90.2%-91.1%). Information channels most commonly reported included television (range: 53.0%-82.0%), newspapers (range: 31.0%-63.0%), official health websites (range: 39.0%-54.1%), and social media (range: 40.0%-55.8%). We observed no major changes in answers over time. Conclusions In European countries, the degree of public belief in the effectiveness of protective measures was high and residents reported to be sufficiently informed by various communication channels. In March 2020, implementation of enacted and self-initiated measures differed between countries and were highest among Italian respondents, who were subjected to the most elaborate measures of social lockdown and greatest COVID-19 burden in Europe.

Abstract Purpose Pituitary diseases severely affect patients’ health-related quality of life (HRQoL). The most frequently used generic HRQoL questionnaire is the Short Form-36 (SF-36). The shorter 12-item version (SF-12) can improve efficiency of patient monitoring. This study aimed to determine whether SF-12 can replace SF-36 in pituitary care. Methods In a longitudinal cohort study (August 2016 to December 2018) among 103 endoscopically operated adult pituitary tumor patients, physical and mental component scores (PCS and MCS) of SF-36 and SF-12 were measured preoperatively, and 6 weeks and 6 months postoperatively. Chronic care was assessed with a cross-sectional study ( N = 431). Mean differences and agreement between SF-36 and SF-12 change in scores (preoperative vs. 6 months) were assessed with intraclass correlation coefficients (ICC) and limits of agreement, depicting 95% of individual patients. Results In the longitudinal study, mean differences between change in SF-36 and SF-12 scores were 1.4 (PCS) and 0.4 (MCS) with fair agreement for PCS (ICC = 0.546) and substantial agreement for MCS (ICC = 0.931). For 95% of individual patients, the difference between change in SF-36 and SF-12 scores varied between −14.0 and 16.9 for PCS and between −7.8 and 8.7 for MCS. Cross-sectional results showed fair agreement for PCS (ICC = 0.597) and substantial agreement for MCS (ICC = 0.943). Conclusions On a group level, SF-12 can reliably reproduce MCS in pituitary patients, although PCS is less well correlated. However, individual differences between SF-36 and SF-12 can be large. For pituitary diseases, alternative strategies are needed for concise, but comprehensive patient-reported outcome measurement.

Abstract Context Insight into the current landscape of patient-reported outcome (PRO) measures (PROM) and differences between PROs and conventional biochemical outcomes is pivotal for future implementation of PROs in research and clinical practice. Therefore, in studies among patients with acromegaly and growth hormone deficiency (GHD), we evaluated (1) used PROMs, (2) their validity, (3) quality of PRO reporting, (4) agreement between PROs and biochemical outcomes, and (5) determinants of discrepancies. Evidence Acquisition We searched 8 electronic databases for prospective studies describing both PROs and biochemical outcomes in acromegaly and GHD patients. Quality of PRO reporting was assessed using the International Society for Quality of Life Research (ISOQOL) criteria. Logistic regression analysis was used to evaluate determinants. Evidence Synthesis Ninety studies were included (acromegaly: n = 53; GHD: n = 37). Besides nonvalidated symptom lists (used in 37% of studies), 36 formal PROMs were used [predominantly Acromegaly Quality of Life Questionnaire in acromegaly (43%) and Quality of Life-Assessment of Growth Hormone Deficiency in Adults in GHD (43%)]. Reporting of PROs was poor, with a median of 37% to 47% of ISOQOL items being reported per study. Eighteen (34%) acromegaly studies and 12 (32%) GHD studies reported discrepancies between PROs and biochemical outcomes, most often improvement in biochemical outcomes without change in PROs. Conclusions Prospective studies among patients with acromegaly and GHD use a multitude of PROMs, often poorly reported. Since a substantial proportion of studies report discrepancies between PROs and biochemical outcomes, PROMs are pivotal in the evaluation of disease activity. Therefore, harmonization of PROs in clinical practice and research by development of core outcome sets is an important unmet need.

Synthetic glucocorticoids are clinically used to treat auto-immune and inflammatory disease. Despite the high efficacy, glucocorticoid treatments causes side effects such as obesity and insulin resistance in many patients. Via their pharmacological target, the glucocorticoid receptor (GR), glucocorticoids suppress endogenous glucocorticoid secretion. Endogenous, but not synthetic, glucocorticoids activate the mineralocorticoid receptor (MR) and side effects of synthetic glucocorticoids may thus not only result from GR hyperactivation but also from MR hypoactivation. Here, we tested the hypothesis that reactivation of MR with corticosterone add-on treatment can attenuate the metabolic effects of the synthetic glucocorticoid dexamethasone. Male 8-week-old C57Bl/6J mice received a high-fat diet supplemented with dexamethasone or vehicle, and were subcutaneously implanted with low-dose corticosterone- or vehicle-containing pellets. Dexamethasone strongly reduced body weight and fat mass gain, while corticosterone add-on partially normalized this. Dexamethasone-induced hyperglycemia and hyperinsulinemia were exacerbated by corticosterone add-on, which was prevented by MR antagonism. In subcutaneous white adipose tissue, corticosterone add-on prevented the dexamethasone-induced expression of intracellular lipolysis genes. In brown adipose tissue, dexamethasone also upregulated gene expression of brown adipose tissue identity markers, lipid transporters and lipolysis enzymes, which was prevented by corticosterone add-on. In conclusion, corticosterone add-on treatment prevents several, while exacerbating other metabolic effects of dexamethasone. While the exact role of MR remains elusive, this study suggests that corticosterone suppression by dexamethasone contributes to its effects in mice.

Endoscopic transsphenoidal surgery causes nasal morbidity and negatively affects health-related quality of life (HRQoL). Knowledge on actionable symptoms that could improve postoperative HRQoL is therefore important. This study assessed the impact of nasal symptoms on postoperative HRQoL.This perioperative cohort study included 103 adult patients undergoing endoscopic pituitary adenoma resection (August 2016-December 2018), with measurements preoperatively, and 5 days, 6 weeks and 6 months after surgery. Nasal symptoms were measured with the Anterior Skull base nasal inventory-12, and HRQoL with the Short Form-36 (SF-36) physical (PCS) and mental component scores (MCS). Linear regression analysis was used to assess (1) determinants of postoperative nasal morbidity, (2) associations between number of symptoms or (3) individual symptoms and HRQoL, and (4) the percentage of variance of HRQoL explained by nasal symptoms.The number of nasal symptoms transiently increased after surgery. No significant treatment- or disease-related determinants of nasal morbidity were identified. The number of nasal symptoms was significantly associated with a lower PCS (β = - 1.0; 95%CI - 1.5, - 0.4), but not with MCS at 6 weeks. Similar results were observed at 6 months. Headaches (42.2%), problems with smell (42.0%), and taste (36.0%) were the most prevalent symptoms, while sense of smell and taste, and nasal discharge showed the strongest associations with HRQoL.Postoperative nasal symptoms, in particular problems with smell and taste, significantly affect pituitary patients' physical HRQoL. Monitoring of these symptoms may aid in determining which patients may benefit from intensified follow-up and treatment, aiming to optimize HRQoL.

De plotselinge omschakeling naar onderwijs op afstand biedt mogelijkheden voor het bestuderen van expertise en professionaliteit van docenten. Hoe de relatie tussen expertise, professionaliteit, en het fysieke klaslokaal werkt, is relevant voor begrip van waaruit expertise en professionaliteit van docenten in het hoger onderwijs precies bestaat. Op basis van een vragenlijst met open vragen onder 536 docenten van een brede universiteit verkent dit artikel wat de link die respondenten leggen tussen onderwijs en de fysieke omgeving zegt over hun expertise en professionaliteit. Daarbij komt naar voren dat het wegvallen van het lokaal vraagt om nieuwe expertiseontwikkeling. Maar óók dat het verzorgen van online onderwijs verder gaat dan een onverwachte situatie waarvan verondersteld kan worden dat experts daarmee goed om kunnen gaan. In alle online onderwijsvormen missen zij bijvoorbeeld het kunnen ‘lezen’ van de zaal en daarmee een belangrijk instrument om het onderwijs aan te passen aan het niveau en de behoeften van studenten. Voor professionaliteit levert het wegvallen van het lokaal daarnaast ook meer fundamentele waardenconflicten op doordat kernelementen van het contact tussen docent en student die inherent bij professioneel docentschap horen verdwijnen.

Abstract Thirty‐eight children (aged 3;7–7;6) and one of their parents took part in a study concerning children's perceptions of their social networks. The study made use of a newly developed instrument—the Support, Control and Maintenance Pictures Interview (SCAMPI). The SCAMPI offers an individualized testing environment, employing computer presentation of questions based on photographs of significant persons familiar to the child. SCAMPI is designed to allow data analysis to be carried out with the aid of built‐in statistical procedures based on permutation and bootstrap techniques that are optimally adapted to the requirements of individualized testing. The study examines the differentiations young children make between persons in their social networks and the functions they fulfil, the level of agreement between children and their parents and the stability of the children's responses.

Throughout the lifespan, defining a clear self-view plays a key role in both self-concept and identity development. Yet, people may encounter problems of self-definition when constructing an image of themselves as result of contrasts or ambiguities in their ideas about themselves. In this study, differences in the occurrence and types of self-definition problems were investigated in a sample of 733 Dutch participants, divided into four groups aged 17, 40, 55, and 70 years respectively. To measure self-definition problems, we developed a self-report instrument that investigated a range of problems drawn from two distinct research traditions: self-concept development and identity formation. The results revealed that participants experienced only a modest number of the presented problems. They showed, nevertheless, a clear age pattern: the adolescents distinguished themselves from the adult age groups by their concern with the problem of multiplicity, whereas during adulthood the problem of personal authenticity gave way to that of existential vacuum in old age. This pattern corresponds well with the temporal profile in the dynamics of lifespan development and Erikson’s model of ego development.

The perceptions, ideas, and feelings we hold of ourselves, whether consciously or not, are a natural, intrinsic part of our daily functioning. They seem a necessary ingredient of our attempts to sustain a basic sense of identity, or as Erikson (1950) described it, to protect a sense of personal continuity, unity, and social recognition. As such, they make us an individual in the eyes of others as well as ourselves. But they are also the orientating instruments by which we try to bring some coherence to our own life or to set out new directions. For psychologists, self-referential processes retain an intriguing, though somewhat elusive character, which makes it difficult to capture them in a single, neat conceptual and empirical framework. In a sense, the content of such processes seems to typify the person one has grown to be. Yet, in another sense, they constitute the foreshadowing of the person one could become. Moreover, in both cases, as James explained, these processes introduce an element of recursivity in the way we experience ourselves, without totally merging with ongoing mental, behavioral, and social processes.

Abstract Purpose Prolactinomas are the most prevalent functioning pituitary adenomas. They affect gonadal function as well as health-related quality of life (HRQoL). This study aimed to report healthcare utilization and costs, including their determinants, for prolactinoma patients. Methods Cross-sectional study of 116 adult prolactinoma patients in chronic care in a Dutch tertiary referral center. Patients completed four validated questionnaires, assessing healthcare utilization and costs over the previous 12 months (Medical Consumption Questionnaire), disease bother and needs (Leiden Bother and Needs Questionnaire Pituitary), HRQoL (Short Form-36), and self-reported health status (EuroQol 5D). Regression analyses were used to assess associations between disease-related characteristics and healthcare utilization and costs. Results Mean age was 52.0 years (SD 13.7) and median follow-up was 15.0 years (IQR 7.6–26.1). Patients visited the endocrinologist (86.2%), general practitioner (37.9%), and ophthalmologist (25.0%) most frequently. Psychological care was used by 12.9% of patients and 5% were admitted to hospital. Mean annual healthcare costs were €1928 (SD 3319), mainly for pituitary-specific medication (37.6% of total costs), hospitalization (19.4%) and specialist care (16.1%). Determinants for higher healthcare utilization and costs were greater disease bother and needs for support, lower HRQoL, elevated prolactin, and longer disease duration, while tumor size, hypopituitarism and adrenal insufficiency were not significantly associated with healthcare utilization and costs. Conclusion Healthcare utilization and costs of prolactinoma patients are related to patient-reported HRQoL, bother by disease and needs for support. Therefore, addressing patients’ HRQoL and needs is a way forward to improve efficiency of care and patients’ health status.

In 1989 a Dutch national guideline on (imminent) miscarriage was developed for use in general practice. A prospective recording study was carried out to determine how the patients evaluated the care they received from general practitioners (GPs) and midwives who agreed to adhere to this (imminent) miscarriage guideline and to determine the aspects that influence this evaluation.GP practices and midwifery practices in The Netherlands.Prospective recording of appointments during 4 consecutive weeks in a diary by patients who contacted their GP or midwife with symptoms of (imminent) miscarriage.Over a period of 12 months, 75 GPs and 43 midwives recorded all patients (n = 407) showing symptoms of (imminent) miscarriage. In total 265 patients had completed at least the first contact in the diary; 200 patients actually recorded all contacts.Most patients gave their GP or midwife a high evaluation score (8.2 or 8.7 respectively). Yet, 20% thought that the care could be improved if the GP or midwife gave more information, was more empathetic and carried out an ultrasound scan. In determining the aspects that have most influence on the patients' evaluation, empathy and support came first, followed by involvement of the patient in decision making, putting her at ease, and the total duration of the contacts. Although patients who wanted a referral gave a lower score, this seems to be of less importance than the above mentioned aspects. Expecting and getting an ultrasound scan did not influence the patient's evaluation.

a Department of Social Psychology, University of Groningen, The Netherlands b Department of Developmental Psychology, University of Groningen, The Netherlands c Department of Special Education, VU University Amsterdam, The Netherlands d Department of Developmental Psychology, VU University Amsterdam, The Netherlands e Department of Pedagogical and Educational Sciences, Utrecht University, The Netherlands f Department of Developmental Psychology, Utrecht University, The Netherlands

Image optimization is a key step in clinical nuclear medicine, and phantoms play an essential role in this process. However, most phantoms do not accurately reflect the complexity of human anatomy, and this presents a particular challenge when imaging endocrine glands to detect small (often subcentimeter) tumors. To address this, we developed a novel phantom for optimization of positron emission tomography (PET) imaging of the human pituitary gland. Using radioactive 3D printing, phantoms were created which mimicked the distribution of 11C-methionine in normal pituitary tissue and in a small tumor embedded in the gland (i.e., with no inactive boundary, thereby reproducing the in vivo situation). In addition, an anatomical phantom, replicating key surrounding structures [based on computed tomography (CT) images from an actual patient], was created using material extrusion 3D printing with specialized filaments that approximated the attenuation properties of bone and soft tissue.The phantom enabled us to replicate pituitary glands harboring tumors of varying sizes (2, 4 and 6 mm diameters) and differing radioactive concentrations (2 ×, 5 × and 8 × the normal gland). The anatomical phantom successfully approximated the attenuation properties of surrounding bone and soft tissue. Two iterative reconstruction algorithms [ordered subset expectation maximization (OSEM); Bayesian penalized likelihood (BPL)] with a range of reconstruction parameters (e.g., 3, 5, 7 and 9 OSEM iterations with 24 subsets; BPL regularization parameter (β) from 50 to 1000) were tested. Images were analyzed quantitatively and qualitatively by eight expert readers. Quantitatively, signal was the highest using BPL with β = 50; noise was the lowest using BPL with β = 1000; contrast was the highest using BPL with β = 100. The qualitative review found that accuracy and confidence were the highest when using BPL with β = 400.The development of a bespoke phantom has allowed the identification of optimal parameters for molecular pituitary imaging: BPL reconstruction with TOF, PSF correction and a β value of 400; in addition, for small (< 4 mm) tumors with low contrast (2:1 or 5:1), sensitivity may be improved using a β value of 100. Together, these findings should increase tumor detection and confidence in reporting scans.

Although the term neuroendocrine is now applied to many different contexts in which the nervous system interacts with the endocrine system to regulate hormone release and bring about important changes in physiology, the hypothalamic–pituitary axis remains the best known and most well-characterised example of a neuroendocrine system. Here, the hypothalamus acts as the major coordinating centre, integrating a diverse array of intrinsic (e.g. higher cortical, autonomic, endocrine) and extrinsic (e.g. environmental) signals to direct the function of multiple different target cells/tissues within the central nervous system, pituitary gland and peripheral sites. Hypothalamic regulation of pituitary function has far-reaching consequences, governing the release of hormones from other key endocrine glands (e.g. adrenal, thyroid, gonad), which, in turn, regulate the function of many physiological pathways with important consequences for energy balance and metabolism, osmo- and thermo-regulation, heart rate and blood pressure control, central nervous system function, growth and reproduction.

SamenvattingPesten op school is waarschijnlijk van alle tijden. In de Engelse letterkunde is bijvoorbeeld de schoolbully op kostscholen een bekende figuur. In de jaren zeventig van de vorige eeuw bleek uit wetenschappelijk onderzoek van Olweus in Scandinavië, dat pesten op grote schaal voorkwam op scholen. Sindsdien is er een toenemende belangstelling voor het onderwerp over de hele wereld waar te nemen, in wetenschappelijk onderzoek en de media. Persoonlijke verhalen van slachtoffers verschijnen in dagbladen, tv-documentaires en op websites.

Evidence was sought for an interaction between both phenotypic and genetic production potential and response of milk production to administration of bST in three trials of 38, 43, and 35 tered in doses of 0, 10.3, 20.6, and, in trial 1 only, 41.2 mg/d for 38 wk from wk 4 of lactation.Data were analyzed for each experiment separately and combined across experiments.Analyses included separate regressions for treated and untreated animals for milk production during the production period on p r e treatment production and estimated breeding value for milk production.Breeding value was estimated as the sire's estimated transmitting ability plus one-half of the m a t d grandsire's estimated transmitting abiity.With the exception of regression on estimated breeding value in trial 1 and in combined data, differences between treated and untreated animals in the regression of milk production on pretreatment milk production or on estimates of breeding value were not statistically significant.However, regressions on pretreatment production were substantially lower for treated than for untreated animals in each of the three trials.Regressions on breeding value estimated from sire and maternal grandsire estimated transmitting abilities were substantially, but not significantly, lower for untreated than for treated animals in all three trials.The results suggest that cows with high production potential for nongenetic reasons may show diminished COWS.In each trial, bST W ~S adminis-

Abstract The present study investigated at what age self‐references would turn up for the first time in young children's language and what kind of words these were. This was studied for a corpus of the first 50 words, produced by ten children, five boys and five girls, collected through parental reports. Self‐references were defined as all words that referred in one way or another to the speakers themselves. They were not restricted to utterances containing pronominals of the first person singular or the child's first name. The appearance of self‐references varied with the onset of speech. Children who started to speak early also produced self‐referent words at an early age (between 12 and 16 months). Self‐references could be satisfactorily classified into three lexical categories: nominals, action words and modifiers, containing words (a) labelling body parts, (b) verbalizing action plans and ongoing actions, and (c) expressing characteristics of outer appearance and actions, and physical sensations, respectively. This indicates that young children's sense of self is not restricted to an awareness of their own actions, but that a variety of experiences contribute to this. Copyright © 2001 John Wiley &amp; Sons, Ltd.

Theory and research on constructs such as the self-concept, which have a considerable history in psychology, are inevitably influenced by prevailing scientific opinions and developments at a particular point in time (Baumeister, 1987; Logan, 1987). In the sixties and seventies the self-concept was a rather unproblematic construct, predominantly handled as a trait: a relatively stable, generalized, cognitive set or system of descriptive features, characteristic of a particular individual. The majority of methods still used to investigate the self-concept, mainly variations of self-esteem questionnaires, underline this view (Byrne, 1996; Wylie, 1989).

Over the years, the topics of self and identity have received a great deal of attention in the field of psychology. The literature is replete with investigations into self-concept, people's perceptions, ideas, and feelings about themselves, and into identity, people's perceptions of their own sameness and continuity (Oosterwegel and Wicklund, 1995). Although researchers in the field choose to focus on different facets of self and identity, broad theoretical trends can be identified.

Abstract Purpose To assess the potential for 11 C-methionine PET (Met-PET) coregistered with volumetric magnetic resonance imaging (Met-PET/MR CR ) to inform clinical decision making in patients with poorly visualized or occult microprolactinomas and dopamine agonist intolerance or resistance. Patients and methods: Thirteen patients with pituitary microprolactinomas, and who were intolerant (n = 11) or resistant (n = 2) to dopamine agonist therapy, were referred to our specialist pituitary centre for Met-PET/MR CR between 2016 and 2020. All patients had persistent hyperprolactinaemia and were being considered for surgical intervention, but standard clinical MRI had shown either no visible adenoma or equivocal appearances. Results In all 13 patients Met-PET/MR CR demonstrated a single focus of avid tracer uptake. This was localized either to the right or left side of the sella in 12 subjects. In one patient, who had previously undergone surgery for a left-sided adenoma, recurrent tumor was unexpectedly identified in the left cavernous sinus. Five patients underwent endoscopic transsphenoidal selective adenomectomy, with subsequent complete remission of hyperprolactinaemia and normalization of other pituitary function; three patients are awaiting surgery. In the patient with inoperable cavernous sinus disease PET-guided stereotactic radiosurgery (SRS) was performed with subsequent near-normalization of serum prolactin. Two patients elected for a further trial of medical therapy, while two declined surgery or radiotherapy and chose to remain off medical treatment. Conclusions In patients with dopamine agonist intolerance or resistance, and indeterminate pituitary MRI, molecular (functional) imaging with Met-PET/MR CR can allow precise localization of a microprolactinoma to facilitate selective surgical adenomectomy or SRS.

Vroom in de Vinex Marten van der Meulen deed onderzoek naar de rol van twee kerkopbouw projecten in de civil society van de Vinex-wijk Leidsche Rijn. Door middel van participerende observatie en andere kwalitatieve methoden onderzocht hij hoe de civil society zich in Leidsche Rijn ontwikkelt en hoe de kerkelijke opbouwprojecten hierin functioneren. Het blijkt dat een lokale civil society zich moeizaam ontwikkelt, en dat de kerkelijke projecten zich in een sociaal vacum bevinden: zij zijn amper verbonden met de professionele sociale infrastructuur die in Leidsche Rijn aan het ontstaan is. Toch hebben de kerken hun eigen visie op wat zij kunnen betekenen. Een van de projecten gebruikt het kapitaal dat besloten ligt in de oude, al bestaande sociale infrastructuur van twee dorpen die in de nieuwbouwwijk liggen. Met dit kapitaal initieert het project een Cultuurcampus, een samenwerking tussen verschillende maatschappelijke instellingen zoals een school, een bibliotheek en het maatschappelijk werk. Het gebruik van dit sociale kapitaal heeft echter niet alleen positieve consequenties: het belemmert ook de reikwijdte van de maatschappelijke participatie. Verder zien de kerkelijke opbouwprojecten mogelijkheden om met een spirituele bijdrage relevant te zijn voor de nieuwbouwbewoner. Deze religieuze visie op civil society stelt vragen bij de visie op maatschappelijke participatie die in de politiek, overheid en maatschappelijk middenveld dominant is, namelijk dat alleen sociaal-culturele functies van religieuze organisaties als maatschappelijke bijdrage gezien mogen worden. Met behulp van de filosoof Charles Taylor stelt Marten van der Meulen een model voor waarin religieuze bijdragen voluit gerekend worden als bijdragen aan de civil society.

Background: Bedaquiline (BDQ) is the first new agent for use in treatment of drug resistant tuberculosis (DR-TB). Studies identified the genetic resistance determinants to be the biological pathway target atpE and efflux based pathway regulating the mmpS5/L5 efflux pump Rv0678. South Africa has been troubled with poor outcomes in drug resistant TB patients prior to the introduction of BDQ. Clinical trials and the compassionate use access program showed improved cure rates for pre-/extensively drug resistant TB patients. In October 2014, BDQ was registered in South Africa and to date >15,000 drug resistant TB patients have been initiated on a BDQ containing regimen. With it's introduction and as part of the national policy framework, the National TB Reference Laboratory, implemented a surveillance programme to monitor the emergence of resistance. In 2018, Ismail et al. proposed tentative critical concentrations for phenotypic drug susceptibility, which were later established by the World Health Organization using multi-country data. In addition, they further identified the efflux based pathway as the sole contributor to resistance for isolates detected as being phenotypically resistant. In this study, we aimed to explore the genetic resistance associated variants (RAV) related to BDQ resistance using the proposed critical concentrations. Methods and materials: Surveillance specimens were prospectively collected from patients initiated on a BDQ treatment regimen at baseline, month 2 and month 6 on treatment between 2014–2019. All mycobacterial cultured isolates from this cohort were phenotypically tested to identify resistance. Phenotypically resistant isolates were then sequenced to identify RAVs in either the Rv0678 or atpE genes. Results: A total of 8041 unique patients were included in this study. Three percent of these isolates were phenotypically resistant, all of which harboured a RAV in the Rv0678 gene. More than 75% of these RAVs were localized to a 100 bp fragment within the genetic target. The underlying genetic mechanism for BDQ resistance in South Africa still remains exclusively related to the Rv0678 genetic target. Conclusion: The exploration of efflux pump inhibitors as a conduit remains relevant. Furthermore, the information may prove useful for development of a rapid molecular screening tool for the detection of BDQ resistance

Abstract Purpose : As the majority of patients with pituitary disease are of working age, their health situation may negatively impact their functioning at work. However, work participation can also be influenced by contextual (environmental and personal) factors. The aim of this qualitative study was to investigate the pituitary patients’ perspective on their functioning at work and on contextual factors contributing to work-related problems using the expanded International Classification of Functioning, Disability and Health (ICF). Methods : Semi-structured interviews, focusing on contextual factors influencing work ability and experience, were conducted with eight patients with different types of pituitary adenomas (Cushing’s disease, prolactinoma, acromegaly, non-functioning adenoma). Following the steps of an experiential thematic analysis, forty categories were identified, which were organized into eleven themes according to the expanded ICF. Results : Patients reported various problems in work-related activities and work participation. Influencing environmental factors included type of employment, perceived job security, financial security, relationships with colleagues/managers, collaboration with others, physical vs. mental work, managing position, flexibility at work, corporate culture, and physical work environment ( work-related ), and traveling distance to work, financial savings, and (non)professional support ( other environmental factors). Influencing personal factors included professional ambition, sense of duty, motivation, job satisfaction, feeling of fulfilment ( work-related ), and personality, acceptance, coping styles, and lifestyle ( general personal factors ). Conclusion : Patients with pituitary disease report several contextual factors that influence their functioning at work. Healthcare and occupational health professionals should be aware of these factors to improve patients’ well-being and functioning at work, ultimately aiming to improve quality of life.

Evidence was sought for an interaction between both phenotypic and genetic production potential and response of milk production to administration of bST in three trials of 38, 43, and 35 tered in doses of 0, 10.3, 20.6, and, in trial 1 only, 41.2 mg/d for 38 wk from wk 4 of lactation. Data were analyzed for each experiment separately and combined across experiments. Analyses included separate regressions for treated and untreated animals for milk production during the production period on pre treatment production and estimated breeding value for milk production. Breeding value was estimated as the sire’s estimated transmitting ability plus one-half of the matd grandsire’s estimated transmitting abiity. With the exception of regression on estimated breeding value in trial 1 and in combined data, differences between treated and untreated animals in the regression of milk production on pretreatment milk production or on estimates of breeding value were not statistically significant. However, regressions on pretreatment production were substantially lower for treated than for untreated animals in each of the three trials. Regressions on breeding value estimated from sire and maternal grandsire estimated transmitting abilities were substantially, but not significantly, lower for untreated than for treated animals in all three trials. The results suggest that cows with high production potential for nongenetic reasons may show diminished COWS. In each trial, bST W~S adminis

Conspiracy-number search (cn search) is an incremental min-max tree-growth algorithm.Experiments suggest that SSS*, a game-tree search algorithm superior to a-~, is a speeial case of cn search.Also, we experimented with 4 parallel cn-search algorithms on a shared-memory MIMD machine: A) a parallel successor evaluation resulting in a speedup of 4.5 on 10 processors; B) dividing subtrees among slave processors achieving a speedup of 3.4; C) a combination of the previous two algorithms with a speedup of 6.3; D) simultaneous search of all processors in the stored game tree yielding a speedup of 4.6.Algorithm A suffers from the costly tree-traversal time in cn search.Algorithm B has a large synchronization overhead.Algorithm C reduces the disadvantages of both algorithms A and B. Algorithm D is degraded by the narrow trees grown by cn search, so processors mutually interfere excessively in the costly updating of nodes.Finally, we tested the strengtlis of the algorithms in a chess program."