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Liabilities of smallness, family relations, leadership style, and preferences are all reasons why owners of small and medium‐sized family enterprises (family SMEs) apply procedures to manage employees inconsistently. For family and non‐family employees of family SMEs, inconsistencies in human resource management (HRM) may be a source of frustration that hampers their performance and wellbeing. Using a sample of 713 respondents in 116 family SMEs, we examined how HRM consistency as a whole, and as three HRM bundles (ability, motivation, and opportunity) could enhance the perceived organizational justice of employees in family SMEs, and whether this differs for family and non‐family employees. We indeed found that HRM consistency is a condition for perceived organizational justice of employees and that this effect was more pronounced for non‐family employees than for family employees. We explain this difference by the distinct environment where the fairness heuristics of employees developed. Where non‐family employees develop their fairness heuristics only in the business sphere, family employees start to develop their fairness heuristics earlier on in the family sphere. We also found evidence that inconsistencies in the motivation‐enhancing HRM bundle were most susceptible to negative perceptions of organizational justice. [ABSTRACT FROM AUTHOR]

Rationale: As cannabis potency and cannabis use are increasing in newly legalized markets, it is increasingly important to measure and examine the effects of cannabinoid exposure. Objectives: The current study aims to assess how hair-derived cannabinoid concentrations – offering insight into three-month cumulative exposure – are associated with common self-report measures of cannabis use and cannabis use-related problems. Methods: 74 near-daily dependent cannabis users self-reported their quantity of cannabis use, cannabis use-related problems, and estimated cannabis potency. Hair samples were provided to quantify Δ9-THC, CBD, and CBN using LC–MS/MS and THC-consumption was verified by analyzing THC-COOH in hair using GC–MS/MS. Results: Cannabinoids were detectable in 95.95% of the hair samples from individuals who tested positive on a urine screen for cannabis. Δ9-THC concentrations were positively associated with measures of self-reported potency (relative potency, potency category, and perceived 'high'), but Δ9-THC, CBD, CBN concentrations and THC/CBD ratio were not associated with self-reported quantity of use. Self-reported potency, but not hair-derived concentrations, were associated with withdrawal and craving. Self-reported quantity of cannabis use, but not cannabinoid concentrations, were associated with cannabis use-related problems. Conclusions: The use of hair-derived cannabinoid quantification is supported for detecting cannabis use in near-daily users, but the lack of associations between hair-derived cannabinoid concentrations and self-report measures of use does not support the use of hair analyses alone for quantification of cannabinoid exposure. Further research comparing hair-derived cannabinoid concentrations with other biological matrices (e.g. plasma) and self-report is necessary to further evaluate the validity of hair analyses for this purpose. [ABSTRACT FROM AUTHOR]

Early diagnosis and treatment of late-onset sepsis (LOS) is crucial for survival, but challenging. Intestinal microbiota and metabolome alterations precede the clinical onset of LOS, and the preterm gut is considered an important source of bacterial pathogens. Fecal volatile organic compounds (VOCs), formed by physiologic and pathophysiologic metabolic processes in the preterm gut, reflect a complex interplay between the human host, the environment, and microbiota. Disease-associated fecal VOCs can be detected with an array of devices with various potential for the development of a point-of-care test (POCT) for preclinical LOS detection. While characteristic VOCs for common LOS pathogens have been described, their VOC profiles often overlap with other pathogens due to similarities in metabolic pathways, hampering the construction of species-specific profiles. Clinical studies have, however, successfully discriminated LOS patients from healthy individuals using fecal VOC analysis with the highest predictive value for Gram-negative pathogens. This review discusses the current advancements in the development of a non-invasive fecal VOC-based POCT for early diagnosis of LOS, which may potentially provide opportunities for early intervention and targeted treatment and could improve clinical neonatal outcomes. Identification of confounding variables impacting VOC synthesis, selection of an optimal detection device, and development of standardized sampling protocols will allow for the development of a novel POCT in the near future. [ABSTRACT FROM AUTHOR]

Introduction Surface guided radiotherapy (SGRT) is increasingly being implemented to track patient's surface movement and position during radiation therapy. However, limited information is available on the SGRT use in paediatrics. The aim of this double survey was to map SIOPE (European Society for Paediatric Oncology)-affiliated centres using SGRT and to gain information on potential indications, observed, or expected benefits. Methods A double online survey was distributed to 246 SIOPE-affiliated radiotherapy (RT) centres. Multiple choices, yes/no, and open answers were included. The first survey (41 questions) was active from February to March 2021. A shortened version (13 questions) was repeated in March 2023 to detect trends in SGRT use within the same community. Results Respectively, 76/142 (54%) and 28/142 (20%) responding centres used and planned to use SGRT clinically, including 4/34 (12%) new centres since 2021. Among the SGRT users, 33/76 (43%) already applied this technology to paediatric treatments. The main benefits of improved patient comfort, better monitoring of intrafraction motion, and more accurate initial patient set-up expected by future users did not differ from current SGRT-users (P  = .893). Among non-SGRT users, the main hurdles to implement SGRT were costs and time for installation. In paediatrics, SGRT is applied to all anatomical sites. Conclusion This work provides information on the practice of SGRT in paediatrics across SIOPE-affiliated RT centres which can serve as a basis for departments when considering the purchase of SGRT systems. Advances in knowledge Since little information is available in the literature on the use of SGRT in paediatrics, the results of this double survey can serve as a basis for departments treating children when considering the purchase of an SGRT system. [ABSTRACT FROM AUTHOR]

Background: Prevalence of nitrous oxide (N2O) use appears to be increasing in numerous countries worldwide, and excessive use has been associated with physical and mental problems. Because there currently is no consensus whether N2O has addictive potential, we aimed to evaluate the evidence for the presence and prevalence of DSM‐5 substance use disorder (SUD) symptoms in N2O users. Analysis: A literature search was conducted to assess the evidence for the presence of any of the 11 DSM‐5 SUD symptoms in N2O users and the prevalence experiencing those symptoms. A substantial part of the studied N2O users use more than intended (i.e. 46% to 98%) and spend a substantial amount of time using N2O. At least some of the studied N2O users experience interpersonal problems (i.e. 13% to 80%) and use N2O in risky situations, such as driving under the influence. Evidence for the other criteria is either insufficient or inconclusive. Conclusions: The literature base for the presence and prevalence of DSM‐5 substance use disorder (SUD) symptoms in nitrous oxide (N2O) users is limited and largely consists of qualitative studies and case studies, but it provides consistent evidence for the presence of at least four SUD criteria in heavy N2O users. N2O could well be addictive and should be treated as a potentially addictive substance until systematic assessments can provide evidence‐based guidance to users, healthcare professionals and legislators. [ABSTRACT FROM AUTHOR]

Stress relaxation of high-density polyethylene is addressed both experimentally and theoretically. Two types of stress relaxation testing are carried out: uniaxial tensile testing at constant test specimen length and compression testing of a 3D structure producing inhomogeneous deformation fields and relaxation. A constitutive model for isotropic, semi-crystalline polymers is also proposed. The model has the ability to model stress relaxation at different time scales. The developed model was implemented as a user subroutine in Abaqus (UMAT). The implicit integration scheme including an algorithmic tangent modulus is described in detail. The material model is calibrated by use of the uniaxial tensile tests, and the model is then validated by simulating the compression tests of the 3D structure. The model is able to describe the uniaxial tension tests well, and the comparison between the simulations and experimental testing of the 3D structure shows very good agreement. [ABSTRACT FROM AUTHOR]

The risk to human health from bacterial foodborne infection is presently controlled by the addition of antimicrobial preservatives to food. However, the use of chemical preservatives such as sodium nitrite poses a health risk in themselves with concerns around carcinogenic effects. This makes the development of improved preservatives a priority for the food industry. One promising source of novel antimicrobial compounds can be found in nature; phytochemicals, in particular polyphenols are secondary metabolites produced by plants for numerous purposes including antimicrobial defence. There has been significant study of phytochemicals; including quantifying their antimicrobial activity, potential to synergise with current antibiotics and the feasibility of their application as natural food preservatives. However, there remains significant uncertainty about the relative antimicrobial efficacy of different phytochemicals, their mechanisms of action (MOA) and the potential for emergence of bacterial resistance to their effects. This review summarizes recent work relevant to the potential development of phytochemicals as antimicrobial agents. [ABSTRACT FROM AUTHOR]

This is an introductory article for the proceedings associated with the Royal Society Hooke discussion meeting of the same title which took place in London in May 2023. We review the history of Penrose's conformal compactification, null infinity and a number of related fundamental developments in mathematical general relativity from the last 60 years. This article is part of a discussion meeting issue 'At the interface of asymptotics, conformal methods and analysis in general relativity'. [ABSTRACT FROM AUTHOR]

A series of well-exposed Paleogene sedimentary successions in the Kohat Basin of northwestern Pakistan (western Himalayas), are used to document the development of Paleogene sedimentary sequence deposited in a clastic–carbonate–evaporate distally steepened to a homoclinal ramp setting. Larger benthic foraminifer stratigraphy, sedimentology and microfacies were used to reconstruct the depth of deposition of the sediments and to aid in reconstructing the subsidence history of the sedimentary basin through the Paleogene. Based on the timing of the cessation of marine sedimentation and the subsidence analysis of the Paleogene rocks of the Kohat Basin, we conclude that a proto-closure of the basin occurred in the early Eocene (Ypresian) at ca 50–49.5 Ma, followed by return of marine sediments, with full closure of the Tethys seaway in the middle Eocene ca 40–41.2 Ma (Lutetian), potentially resulting in diachroneity of emergence of basins along strike of the orogen. Paleogene Larger Benthic Foraminferal biostratigrphy and facies information in the Eastern Tethys segment of the Kohat Basin, Pakistan are presented. Distally steepened-homoclinal ramp deposits were found. The proto-closure of Tethys occurred around 49.5 Ma with complete closure at 41.2–40 Ma due to India-Asia collision. [ABSTRACT FROM AUTHOR]

The study aimed to test the efficacy of the core elements of the Health Action Process Approach (HAPA) in an intervention among parents to promote regular supervised toothbrushing of preschool‐aged children. The pre‐registered study (https://osf.io/fyzh3/) tested the effects of an intervention employing information provision, behavioural instruction, implementation intention and mental imagery techniques, adopting a randomised controlled design in a sample of Australian parents of preschoolers (N = 254). The intervention used an additive design with four conditions—education, self‐efficacy, planning and action control—progressively layered to show the cumulative impact of incorporating self‐efficacy, planning and action control strategies with a foundational education component. The intervention was delivered online, and participants completed self‐report measures of parental supervised toothbrushing and HAPA‐based social cognition constructs pre‐intervention and 4 weeks post‐intervention. Although no significant intervention effects on behaviour were observed, mixed‐model analyses of variance (ANOVAs) revealed an increase in intention and task self‐efficacy within the action control condition and an increase in action planning in both the action control and planning conditions from pre‐intervention to follow‐up. Despite no anticipated changes in behaviour, these findings endorse the use of theory‐ and evidence‐based behaviour change strategies to inspire change in HAPA‐based determinants of parental supervised toothbrushing: intention, action planning and task self‐efficacy. [ABSTRACT FROM AUTHOR]

Risk driver contributions are key to understanding portfolio risk. Often, this is done by decomposing portfolio volatility. This is problematic in the presence of non-elliptical distributions. Some asset managers propose switching to value-at-risk (VaR) or expected shortfall (ES) as risk measures. Often the latter is preferred as it deals better with risk in sub-portfolios. However, we argue that the traditional asset management industry should, as a rule, 'not' apply ES directly. Instead, expected portfolio return should be first subtracted from it; this Centred Expected Shortfall (CES) forms a natural extension of volatility. The relative breakdowns of both are identical if the underlying multivariate distribution is elliptical. From a practical perspective, we show how to correctly decompose CES and how ES can be misleading. Moreover, we recommend plotting so-called alpha-CES/volatility profiles. These work with distribution-free risk estimates and give a bird's eye view on the downside impacts of any non-ellipticalities as a function of the portfolio's left tail size (alpha). Conveniently, these profiles also describe upside tail (surplus) risks. We end with two practical illustrations: A simple assets-only example based on historical data with assets as risk drivers; and a more complex Liability-Driven Investing (LDI) simulation example with factors as drivers. [ABSTRACT FROM AUTHOR]

"The End of This World: Climate Justice in So-Called Canada" is a book that explores the current climate crisis in Canada through an indigenous-centered, decolonial lens. The authors argue that repairing relationships with indigenous peoples and putting indigenous rights and sovereignty at the center of proposals and policies is crucial for a just transition. The book outlines the history of broken promises and political decisions that have led to the climate crisis, as well as indigenous-informed solutions and paths forward. It emphasizes the importance of collaboration, indigenous governance, and concrete actions in addressing the climate crisis. [Extracted from the article]

Background: Patients with bacterial meningitis can be severely ill necessitating intensive care unit (ICU) treatment. Here, we describe clinical features and prognostic factors of adults with bacterial meningitis admitted to the ICU in a nationwide prospective cohort study. Methods: We prospectively assessed clinical features and outcome of adults (age > 16 years) with community-acquired bacterial meningitis included in the MeninGene study between March 1, 2006 and July 1, 2022, that were initially admitted to the ICU. We identified independent predictors for initial ICU admission and for unfavourable outcome (Glasgow Outcome Scale score between 1–4) by multivariable logistic regression. Results: A total of 2709 episodes of bacterial meningitis were included, of which 1369 (51%) were initially admitted to the ICU. We observed a decrease in proportion of patients being admitted to the ICU during the Covid-19 pandemic in 2020 (decreased to 39%, p = 0.004). Median age of the 1369 patients initially admitted to the ICU was 61 years (IQR 49–69), and the rates of unfavourable outcome (47%) and mortality (22%) were high. During the Covid-19 pandemic, we observed a trend towards an increase in unfavourable outcome. Prognostic factors predictive for initial ICU admission were younger age, immunocompromised state, male sex, factors associated with pneumococcal meningitis, and those indicative of systemic compromise. Independent predictors for unfavourable outcome in the initial ICU cohort were advanced age, admittance to an academic hospital, cranial nerve palsies or seizures on admission, low leukocyte count in blood, high C-reactive protein in blood, low CSF: blood glucose ratio, listerial meningitis, need for mechanical ventilation, circulatory shock and persistent fever. 204 of 1340 episodes (15%) that were initially not admitted to the ICU were secondarily transferred to the ICU. The rates of unfavourable outcome (66%) and mortality (30%) in this group were high. Conclusions: The majority of patients with community-acquired bacterial meningitis are admitted to the ICU, and the unfavourable outcome and mortality rates of these patients remain high. Patients that are initially admitted to non-ICU wards but secondarily transferred to the ICU also had very high rates of unfavourable outcome. [ABSTRACT FROM AUTHOR]

The topic of fictional objects and their nature is a familiar one, the topic of fictional properties less so. This article focuses on the way artefactualism – now arguably the most popular form of realism about fictional objects – might be extended to give an account of fictional properties. After describing what seems the most developed such extension, the article articulates a serious problem it faces, before showing how artefactualism about fictional properties would benefit from certain insights contained in an alternative abstract-object version of fictional realism. [ABSTRACT FROM AUTHOR]

Introduction: Clinical practice guidelines (hereafter 'guidelines') are crucial in providing evidence‐based recommendations for physicians and multidisciplinary teams to make informed decisions regarding diagnostics and treatment in various diseases, including cancer. While guideline implementation has been shown to reduce (unwanted) variability and improve outcome of care, monitoring of adherence to guidelines remains challenging. Real‐world data collected from cancer registries can provide a continuous source for monitoring adherence levels. In this work, we describe a novel structured approach to guideline evaluation using real‐world data that enables continuous monitoring. This method was applied to endometrial cancer patients in the Netherlands and implemented through a prototype web‐based dashboard that enables interactive usage and supports various analyses. Method: The guideline under study was parsed into clinical decision trees (CDTs) and an information standard was drawn up. A dataset from the Netherlands Cancer Registry (NCR) was used and data items from both instruments were mapped. By comparing guideline recommendations with real‐world data an adherence classification was determined. The developed prototype can be used to identify and prioritize potential topics for guideline updates. Results: CDTs revealed 68 data items for recording in an information standard. Thirty‐two data items from the NCR were mapped onto information standard data items. Four CDTs could sufficiently be populated with NCR data. Conclusion: The developed methodology can evaluate a guideline to identify potential improvements in recommendations and the success of the implementation strategy. In addition, it is able to identify patient and disease characteristics that influence decision‐making in clinical practice. The method supports a cyclical process of developing, implementing and evaluating guidelines and can be scaled to other diseases and settings. It contributes to a learning healthcare cycle that integrates real‐world data with external knowledge. [ABSTRACT FROM AUTHOR]

Using ideas proposed in Aboutness and developed in 'If-thenism', Stephen Yablo has tried to improve on classical if-thenism in mathematics, a view initially put forward by Bertrand Russell in his Principles of Mathematics. Yablo's stated goal is to provide a reading of a sentence like 'The number of planets is eight' with a sort of content on which it fails to imply 'Numbers exist'. After presenting Yablo's framework, our paper raises a problem with his view that has gone virtually unnoticed in the literature. If we are right, then Yablo's version of if-thenism cannot succeed. [ABSTRACT FROM AUTHOR]

A recent editorial in the IUCr macromolecular crystallography journals [Helliwell et al. (2019), Acta Cryst. D75, 455–457] called for the implementation of the FAIR data principles. This implies that the authors of a paper that describes research on a macromolecular structure should make their raw diffraction data available. Authors are already used to submitting the derived data (coordinates) and the processed data (structure factors, merged or unmerged) to the PDB, but may still be uncomfortable with making the raw diffraction images available. In this paper, some guidelines and instructions on depositing raw data to Zenodo are given. [ABSTRACT FROM AUTHOR]

The topic of fictional objects is a familiar one, the topic of fictional properties less so. But it deserves its own place in the philosophy of fiction, if only because fictional properties have such a prominent role to play in science fiction and fantasy. What, then, are fictional properties and how does their apparent unreality relate to the unreality of fictional objects? The present paper explores these questions in the light of familiar debates about the nature of fictional objects. [ABSTRACT FROM AUTHOR]

Cribriform architecture has been recognised as an independent parameter for prostate cancer outcome. Little is yet known on the added value of individual Gleason 5 growth patterns. Comedonecrosis is assigned Gleason pattern 5 and can occur in both invasive and intraductal carcinoma. The aim of this study is to systematically review the literature for the prognostic value of comedonecrosis in prostate cancer. A systematic literature search of Medline, Web of Science, Cochrane library and Google scholar was performed according to the Preferred reporting items for systematic reviews and meta‐analysis (PRISMA)guidelines. After identification and screening of all relevant studies published up to July 2022, 12 manuscripts were included. Clinicopathological data were extracted and the presence of comedonecrosis in either invasive, intraductal or ductal carcinoma was associated with at least one clinical outcome measure. No meta‐analysis was performed. Eight of 11 studies showed that comedonecrosis was significantly associated with biochemical recurrence and two studies with metastasis or death. The only studies using metastasis‐free and disease specific‐free survival as an endpoint both found comedonecrosis to be an independent prognostic parameter in multivariate analysis. The studies were all retrospective and demonstrated considerable heterogeneity with regard to clinical specimen, tumour type, grade group, correction for confounding factors and endpoints. This systematic review demonstrates weak evidence for comedonecrosis to be associated with adverse prostate cancer outcome. Study heterogeneity and lack of correction for confounding factors prohibit drawing of definitive conclusions. [ABSTRACT FROM AUTHOR]

The Solarpunk Conference was a successful virtual event that aimed to bridge the gap between academic and popular conversations surrounding solarpunk, a social movement focused on imagining sociopolitical and economic realities beyond late-stage capitalist neoliberalism. The conference was accessible to a wide range of people, with tickets available at various price points and live captioning and accessibility options provided. The event also facilitated networking and community building through a Discord server. Presentations covered topics such as solarpunk literature, hacktivism, sustainable hydroponics, transformative ecological education, and writing climate fiction. The conference emphasized the importance of addressing climate grief and taking direct action to combat the negative effects of contemporary capitalism. The event concluded with a solarpunk short film debut and a musical performance. The conference provided a valuable space for solarpunks to exchange ideas and learn from each other's visions of utopia. [Extracted from the article]

Persons living with HIV (PLWH) have an increased risk for tuberculosis (TB). After prolonged and repeated exposure, some PLWH never develop TB and show no evidence of immune sensitization to Mycobacterium tuberculosis (Mtb) as defined by persistently negative tuberculin skin tests (TST) and interferon gamma release assays (IGRA). This group has been identified and defined as HIV+ persistently TB, tuberculin and IGRA negative (HITTIN). To investigate potential innate mechanisms unique to individuals with the HITTIN phenotype we compared their neutrophil Mtb infection response to that of PLWH, with no TB history, but who test persistently IGRA positive, and tuberculin positive (HIT). Neutrophil samples from 17 HITTIN (PMNHITTIN) and 11 HIT (PMNHIT) were isolated and infected with Mtb H37Rv for 1h and 6h. RNA was extracted and used for RNAseq analysis. Since there was no significant differential transcriptional response at 1h between infected PMNHITTIN and PMNHIT, we focused on the 6h timepoint. When compared to uninfected PMN, PMNHITTIN displayed 3106 significantly upregulated and 3548 significantly downregulated differentially expressed genes (DEGs) (absolute cutoff of a log2FC of 0.2, FDR < 0.05) whereas PMNHIT demonstrated 3816 significantly upregulated and 3794 significantly downregulated DEGs following 6h Mtb infection. Contrasting the log2FC 6h infection response to Mtb from PMNHITTIN against PMNHIT, 2285 genes showed significant differential response between the two groups. Overall PMNHITTIN had a lower fold change response to Mtb infection compared to PMNHIT. According to pathway enrichment, Apoptosis and NETosis were differentially regulated between HITTIN and HIT PMN responses after 6h Mtb infection. To corroborate the blunted NETosis transcriptional response measured among HITTIN, fluorescence microscopy revealed relatively lower neutrophil extracellular trap formation and cell loss in PMNHITTIN compared to PMNHIT, showing that PMNHITTIN have a distinct response to Mtb. Author summary: Neutrophils can contribute to the severity of tuberculosis (TB). More recently TB protective mechanisms of neutrophils have also been highlighted. We examined the gene expression of neutrophils, one of the first immune cells to make contact with Mycobacterium tuberculosis (Mtb), the causative organism of TB, once Mtb is inhaled. Our study used two populations: i) persons who are living with HIV (PLWH), have no history of TB and test persistently negative for Mtb T cell sensitization (HITTIN); and ii) PLWH who have a positive Mtb-specific T cell response with no previous TB (HIT). Specifically, we compared neutrophil response to Mtb and compared HITTIN to HIT. Compared to neutrophils from HIT persons, HITTIN neutrophils (PMNHITTIN) show significant gene expression differences in response to Mtb infection. Unexpectedly, our results show PMNHITTIN have a global lower response to Mtb infection with fluorescent microscopy revealing lower neutrophil extracellular trap (NET) formation in PMNHITTIN compared to PMNHIT after 6h infection with Mtb. NETs are weblike structures and are formed from decondensed DNA during a unique form of cell death named NETosis. This data highlights PMNHITTIN as important immune cells in response to Mtb in HITTIN. [ABSTRACT FROM AUTHOR]

Maternal prenatal distress (i.e., anxiety and depressive symptoms) increases the risk for childhood behavioral and emotional problems. So far, the potential role of maternal bonding in this association still needs further study. Maternal prenatal distress can affect the development of maternal bonding from pregnancy onwards. Maternal prenatal and postnatal bonding in turn have been shown to predict child behavioral functioning. We aimed to investigate whether maternal prenatal and postnatal bonding mediate the association between maternal prenatal distress and toddlers' internalizing and externalizing problems. Data from a Dutch prospective longitudinal sample (N = 666) were used to conduct single and multiple mediation models. Mothers reported prenatal anxiety (State Anxiety Inventory) and prenatal depressive symptoms (Edinburgh Postnatal Depression Scale) at 24 weeks' gestation and maternal prenatal bonding (Maternal Antenatal Attachment Scale) at 32 weeks' gestation. At 6 weeks and 6 months postpartum mothers completed questionnaires to assess maternal postnatal bonding (Maternal Postnatal Attachment Scale). Mothers reported child internalizing and externalizing problems (Child Behavior Checklist) at 28 months postpartum. Maternal prenatal and postnatal bonding mediated the link between maternal prenatal anxiety and child externalizing problems but not internalizing problems. Only maternal bonding 6 months postpartum mediated the link between maternal prenatal depressive symptoms and child internalizing problems but not externalizing problems. Our study showed that maternal postnatal bonding more consistently mediated links between measures of maternal prenatal distress and child behavioral and emotional problems than maternal prenatal bonding. Interventions reducing maternal prenatal distress and promoting maternal bonding should be developed. Highlights: We examined whether maternal pre- and postnatal bonding mediated links between maternal prenatal distress and child behavioral problems Bonding 6 months postpartum mediated the link between prenatal distress and child behavioral and emotional problems Only the link between prenatal anxiety and child externalizing problems was serially mediated by prenatal bonding and bonding 6 months postpartum Postnatal bonding more consistently mediated links between prenatal distress and child behavioral problems than prenatal bonding [ABSTRACT FROM AUTHOR]

Background: To offer optimal care, the mental health system needs new routes for collaboration, involving both interprofessional and interorganizational aspects. The transition from intramural to extramural mental health care has given rise to new dynamics between public and mental health care, introducing a challenge for interprofessional and interorganizational collaboration. This study aims to determine values and expectations of collaboration and to understand how collaboration in mental health care organizations takes shape in daily practice. Methods: We conducted a qualitative study using semi-structured interviews and a focus group, in the setting of the Program for Mentally Vulnerable Persons (PMV). Data were analysed following thematic analysis. Results: We found three aspect that were considered important in collaboration: commonality, relationships, and psychological ownership. However, our findings indicate a discrepancy between what is considered essential in collaboration and how this materializes in day-to-day practice: collaboration appears to be less manageable than anticipated by interviewees. Our data suggest psychological ownership should be added as value to the interorganizational collaboration theory. Conclusion: Our study offers a new definition of collaboration and adding "psychological ownership" to the existing literature on collaboration theory. Furthermore, we gained insight into how collaboration between different organizations works in practice. Our research points to a discrepancy between what all the partners find important in collaboration, and what they actually do in practice. Finally, we expressed ways to improve the collaboration, such as choosing between a chain or a network approach and acting on it and re-highlighting the goal of the Program Mentally Vulnerable persons. [ABSTRACT FROM AUTHOR]

Cannabis legislation and attitudes towards use are changing. Given that evidence from cultural neuroscience research suggests that culture influences the neurobiological mechanisms underlying behaviour, it is of great importance to understand how cannabis legislation and attitudes might affect the brain processes underlying cannabis use disorder. Brain activity of 100 dependent cannabis users and 84 controls was recorded during an N‐back working memory (WM) task in participants from the Netherlands (NL; users = 60, controls = 52) and Texas, USA (TX; users = 40, controls = 32). Participants completed a cannabis culture questionnaire as a measure of perceived benefits (positive) and perceived harms (negative) of cannabis from their personal, friends–family's and country–state's perspectives. Amount of cannabis use (grams/week), DSM‐5 CUD symptoms and cannabis use‐related problems were assessed. Cannabis users self‐reported more positive and less negative (personal and friends–family) cannabis attitudes than controls, with this effect being significantly larger in the TX cannabis users. No site difference in country–state attitudes was observed. TX cannabis users, compared with NL cannabis users, and those cannabis users perceiving more positive country–state attitudes showed a more positive association between grams/week and WM‐related activity in the superior parietal lobe. NL cannabis users, compared with TX cannabis users, and those cannabis users with less positive personal attitudes showed a more positive association between grams/week and WM‐load‐related activity in the temporal pole. Both site and cultural attitudes moderated the association of quantity of cannabis use with WM‐ and WM‐load‐related activity. Importantly, differences in legislation did not align with perceived cannabis attitudes and appear to be differentially associated with cannabis use‐related brain activity. [ABSTRACT FROM AUTHOR]

Dynamical black holes in the non-perturbative regime are not mathematically well understood. Studying approximate symmetries of spacetimes describing dynamical black holes gives an insight into their structure. Utilising the property that approximate symmetries coincide with actual symmetries when they are present allows one to construct geometric invariants characterising the symmetry. In this paper, we extend Dain's construction of geometric invariants characterising stationarity to the case of initial data sets for the Einstein equations corresponding to black hole spacetimes. We prove the existence and uniqueness of solutions to a boundary value problem showing that one can always find approximate Killing vectors in black hole spacetimes and these coincide with actual Killing vectors when they are present. In the time-symmetric setting we make use of a 2 + 1 decomposition to construct a geometric invariant on a marginally outer trapped surface that vanishes if and only if the Killing initial data equations are locally satisfied. [ABSTRACT FROM AUTHOR]

The social plasticity hypothesis proposes that social attunement, that is, the adaptation to and harmonization with one's environment, plays a crucial role in the risk for developing alcohol use disorders (AUDs) during adolescence, whereas in adulthood it paradoxically may make individuals more sensitive to the social pull to reduce drinking. This study aimed to develop a valid measure of social attunement: the social attunement questionnaire (SAQ). A total of 26 items were developed and the questionnaire was completed by 576 Dutch mid to late adolescents and adults over three rounds of online data collection. Using exploratory factor analysis in part of the sample (N = 373), the final questionnaire was reduced to two subscales with a total of 11 items. This structure was confirmed using confirmatory factor analysis in the second part of the sample (N = 203). Results showed that the SAQ has acceptable internal consistency, good measurement invariance to gender, and subscales assessing both cognitive as well as behavioural components of social attunement. In line with expectations on alcohol use settings, SAQ scores were not associated directly with alcohol use, but they were predictive of alcohol use when taking into account the interaction between perceived peer drinking and age. The SAQ appears suitable for the assessment of social attunement in (young) adult men and women, particularly assessing the role of social attunement in alcohol use settings. Further research is needed to confirm the utility of the SAQ in older adults and a broader variety of social settings. [ABSTRACT FROM AUTHOR]

Purpose: To present the first pediatric study on the safety and efficacy of mastoid obliteration using S53P4 bioactive glass (BAG) for cholesteatoma surgery. Methods: A single-center retrospective cohort study was conducted. Inclusion criteria were pediatric cases (≤ 18 years) and at least at least one year of follow-up including non-echo planar diffusion-weighted MRI to assess cholesteatoma recidivism. Both canal wall up (CWU) and canal wall down (CWD) procedures were evaluated. Results: A total of 61 cases (56 patients) were included. Most cases had an otologic history before the development of the cholesteatoma. CWU procedure was performed in 18 cases (30%) and CWD procedure in 43 cases (70%). The cholesteatoma recidivism rate was 33% after a mean follow-up period of 58 months. Kaplan–Meier curve estimated a 5-year recidivism rate of 40%. Few complications were seen that were all minor and resolved spontaneously or after local or systemic treatment. Control of the infection (merchant grade 0–1) was achieved in 98% of the cases. Closure of the air–bone gap within 20 dB was achieved in 22% of the cases with complete audiometric evaluation. Conclusion: In this MRI-controlled study, we show the safety and efficacy of S53P4 BAG for mastoid obliteration in a pediatric cholesteatoma cohort. Postoperative complications were both rare and minor, and a dry ear was achieved in almost all patients. Nevertheless, persistent hearing loss and the apparent high recidivism rate reflect the challenging nature of pediatric cholesteatoma. [ABSTRACT FROM AUTHOR]

Background Parental health literacy may explain the relationship between parental socioeconomic status (SES) and paediatric metabolic syndrome (MetS). For this reason, we assessed to what extent parental health literacy mediates the relationships between parental SES and paediatric MetS. Methods We used data from the prospective multigenerational Dutch Lifelines Cohort Study. Our sample consisted of 6683 children with an average follow-up of 36.2 months (SD 9.3) and a mean baseline age of 12.8 years (SD 2.6). We used natural effects models to assess the natural direct, natural indirect and total effects of parental SES on MetS. Results On average, an additional 4 years of parental education, e.g. university instead of secondary school, would lead to continuous MetS (cMetS) scores that were 0.499 (95% confidence interval (CI): 0.364–0.635) units lower, which is a small effect (d : 0.18). If parental income and occupational level were 1 SD higher, on average cMetS scores were 0.136 (95% CI: 0.052–0.219) and 0.196 (95% CI: 0.108–0.284) units lower, respectively; these are both small effects (d : 0.05 and 0.07, respectively). Parental health literacy partially mediated these pathways; it accounted for 6.7% (education), 11.8% (income) and 8.3% (occupation) of the total effect of parental SES on paediatric MetS. Conclusions Socioeconomic differences in paediatric MetS are relatively small, the largest being by parental education. Improving parental health literacy may reduce these inequalities. Further research is needed into the mediating role of parental health literacy on other socioeconomic health inequalities in children. [ABSTRACT FROM AUTHOR]

Objectives To investigate whether biomarkers are modulated by prednisolone treatment in patients with hand OA and whether they can predict response to prednisolone. Methods Biomarkers reflecting tissue turnover and inflammation [aggrecanase-derived neoepitope of arggecan (ARGS), MMP-derived neoepitope of type I collagen (C1M), MMP-derived neoepitope of type III collagen (C3M), marker of true type V collagen formation (PROC5), MMP-derived neoepitope of CRP (CRPM), citrullinated vimentin fragment (VICM), high-sensitivity (hsCRP)] were measured in sera from 78 patients with painful inflammatory hand OA, who were randomized between prednisolone or placebo treatment. Association of baseline biomarker levels with disease characteristics [visual analogue scale (VAS) pain, synovial thickening ultrasonography sum score and erosive OA] and OMERACT-Osteoarthritis Research Society International (OARSI) response after 6 weeks were analysed with linear or logistic regression and adjusted for age, BMI and sex. Change in biomarker levels after 6 weeks was assessed with linear regression adjusted for baseline biomarker levels, age, BMI and sex. Results For all patients (mean age 64 years, 79% female), there were no associations between biomarker levels and VAS finger pain or synovial thickening score at baseline. Patients with erosive hand OA had higher levels of C1M and hsCRP [adjusted geometric mean ratio 1.24 (95% CI 1.03, 1.49) and 1.91 (1.19, 3.06), respectively]. Biomarker levels did not decrease over time. There was no association between baseline biomarkers levels and OARSI response, except for CRPM [geometric mean ratio of 0.88 (0.77, 1.00)]. Conclusion Erosive disease was associated with higher levels of C1M and hsCRP. Biomarker levels were not influenced by treatment with prednisolone. Current biomarkers were not associated with response to prednisolone in hand OA. [ABSTRACT FROM AUTHOR]

Background: Pulmonary arteriovenous malformations (PAVMs) are direct connections between the pulmonary artery and the pulmonary vein, mostly associated with hereditary haemorrhagic telangiectasia (HHT). PAVMs can lead to severe neurological complications - such as stroke and brain abscess. The risk of complications decreases after embolisation. Therefore, screening for PAVMs using transthoracic contrast echocardiography (TTCE) is recommended, including a rescreening interval of 5 years.Research Question: Is extension of the interval for re-screening patients without a pulmonary right-to-left shunt (RLS) up to ten years appropriate?Study Design and Methods: Adult HHT patients with five- and/ or ten-year follow-up TTCE were included. Patients who underwent PAVM embolisation in the past or at baseline were excluded. The RLS grades and presence of a treatable PAVM were compared to baseline.Results: In total, 387 patients (median age 45 years (IQR 33-54), 56% female) involving five- and ten-year follow-up data in respectively 363 and 166 patients were included. None of the patients (n=148) without a pulmonary RLS at baseline developed a treatable PAVM after five and ten years. Of the patients with a pulmonary RLS at baseline, 20 (9%) and 3 (3%) developed a treatable PAVM at five- and ten-year follow-up respectively. In the majority of patients, the RLS grade remained stable over time.Interpretation: On the basis of the results of this retrospective study, we believe that the rescreening interval for HHT patients without a pulmonary RLS at initial screening may be extended to ten years. Those with a pulmonary RLS should be rescreened every five years because treatable PAVMs can evolve. [ABSTRACT FROM AUTHOR]

Glucocorticoid stress hormones are produced in response to hypothalamic-pituitary-adrenal (HPA) axis activation. Glucocorticoids are essential for physiology and exert numerous actions via binding to the glucocorticoid receptor (GR). Relacorilant is a highly selective GR antagonist currently undergoing a phase 3 clinical evaluation for the treatment of endogenous Cushing's syndrome. It was found that increases in serum adrenocorticotropic hormone (ACTH) and cortisol concentrations after relacorilant treatment were substantially less than the increases typically observed with mifepristone, but it is unclear what underlies these differ ences. In this study, we set out to further preclinically characterize relacorilant in comparison to the classical but non-selective GR antagonist mifepristone. In human HEK-293 cells, relacorilant potently antagonized dexamethasone- and cortisol-induced GR signaling, and in human peripheral blood mononuclear cells, relacorilant largely prevented the anti-inflammatory effects of dexamethasone. In mice, relacorilant treatment preven ted hyperinsulinemia and immunosuppression caused by increased corticosterone exposure. Relacorilant treatment reduced the expression of classical GR target genes in peripheral tissues but not in the brain. In mice, relacorilant induced a modest disinhibition of the HPA axis as compared to mifepristone. In line with this, in mouse pituitary cells, relacorilant was generally less potent than mifepristone in regulating Pomc mRNA and ACTH release. This contrast between relacorilant and mifepristone is possibly due to the distinct transcriptional coregulator recruitment by the GR. In conclusion, relacorilant is thus an efficacious peripheral GR antagonist in mice with only modest dis inhibition of the HPA axis, and the distinct properties of relacorilant endorse the potential of selective GR antagonist treatment for endogenous Cushing's syndrome. [ABSTRACT FROM AUTHOR]

Aims: Cognitive and motivational processes are thought to underlie cannabis use disorder (CUD), but research assessing how cognitive processes [e.g. interference control (IC)] interact with implicit [e.g. attentional bias (AB)] and explicit motivation (i.e. craving) is lacking. We assessed the presence of AB in cannabis users with varying use severity and tested models of moderation, mediation and moderated mediation to assess how AB, craving and IC interact in their association with measures of cannabis use. Design: A cross‐sectional study design was used. Setting and participants: Eight studies performed by our laboratory in the Netherlands including never‐sporadic, occasional (≤ 1/month) and regular cannabis users (≥ 2/week), and individuals in treatment for CUD were combined (n = 560; 71% male). Measurements Studies included a classic Stroop task (IC), a cannabis Stroop task (AB) and measures of session‐induced and average session craving. Both heaviness of cannabis use (grams/week) and severity of use related problems were included. Findings Only those in treatment for CUD showed an AB to cannabis (P = 0.019) and group differences were only observed when comparing CUD with never‐sporadic users (P = 0.007). In occasional and regular users, IC was negatively associated with heaviness (β = 0.015, P < 0.001), but not severity of use. Average session craving (exploratory), but not session‐induced craving (confirmatory), mediated this association between AB and heaviness (β = 0.050, P = 0.011) as well as severity of use (β = 0.083, P = 0.009); higher AB was associated with heavier use and more severe problems through increased craving. Conclusions: Attentional bias only appears to be present in cannabis users with the most severe problems and craving appears to mediate the association between attentional bias and both heaviness and severity of use in occasional and regular users. The association of interference control with heaviness but not severity of use may point to subacute intoxication effects of cannabis use on interference control. [ABSTRACT FROM AUTHOR]

Background: Tobacco smoking and alcohol consumption before and during pregnancy increase the risk of adverse health outcomes for mother and child. Interventions to address smoking and drinking before and during pregnancy have the potential to reduce early-life health inequalities. In the Smoke and Alcohol Free with EHealth and Rewards (SAFER) pilot study we aimed to evaluate the acceptability, feasibility and effectiveness of a complex intervention supporting women in smoking and alcohol cessation before and during pregnancy. Methods: From February 2019 till March 2021, we piloted the SAFER pregnancy intervention among pregnant women and women planning pregnancy in South-West Netherlands in an uncontrolled before-after study. Participants were supported in smoking and alcohol cessation via up to six group sessions and an online platform. In addition, biochemically validated cessation was rewarded with incentives (i.e. shopping vouchers) amounting up to 185 euros. We aimed to include 66 women. The primary outcome was smoking and/or alcohol cessation at 34–38 weeks of gestation (if pregnant) or after six group sessions (if not pregnant). Quantitative data were analysed using descriptive statistics. Focus group interviews among those involved in the study were conducted at the end of the study to explore their experiences. Qualitative data was analysed using thematic analysis. Results: Thirty-nine women who smoked were included; no women who consumed alcohol were referred to the study. Unemployment (51%), financial problems (36%) and a smoking partner (72%) were common. Thirteen women (33%) dropped out, often due to other problems impeding smoking cessation or 'being too busy' to participate in the group sessions. Eleven women (28%) had quit smoking at the study's endpoint. The personal and positive approach was highly valued and biochemical validation was felt to be helpful. Conclusion: The SAFER pregnancy intervention seems appropriate for women in need of extra support for smoking cessation before and during pregnancy. Its impact on alcohol cessation could not be studied due to recruitment issues. Recruitment and prevention of early dropout need attention in further development of this intervention. Trial registration: Netherlands Trial Register: NL7493. Date registered: 04/02/2019. [ABSTRACT FROM AUTHOR]

Many organizations have embraced agile methods. Studies show a trend of large-scale application of agile frameworks company-wide. Emergent architecture design as part of an agile approach is effective at the project level but causes issues when services need to interact seamlessly at the enterprise level. Enterprise architecture (EA) can provide such coherence. Combining the scaling agile methods with EA is challenging. However, such a combination could benefit from the flexibility that agile approaches offer and provide the consistency and long-term focus that EA pursues. This article uses the longitudinal case study research to explore how organizations can effectively govern Agile and EA in large-scale agile transformations. Our case analysis shows that methods for scaling Agile do not provide sufficient guidance to properly handle the transformation from existing EA practices to an Agile EA combination company-wide. We propose how EA can be applied effectively in large-scale agile transformations despite the two seemingly conflicting approaches of Agile and EA. Based on our findings, we propose a conceptual model for future research that incorporates factors that take EA into account in the governance of agile-scaling frameworks. Our findings extend current literature on coordination mechanisms between architects and agile teams in large-scale agile transformations, thereby balancing emergent and intentional architectures. [ABSTRACT FROM AUTHOR]

This study brings together an interest in contemporary gambling advertising, national regulatory impacts on such advertising, and the ways in which gender, in combination with ethnicity, operate in such advertising. The paper's aim is to explore the interplay between state and self-regulations of gambling advertising and the concrete design of these advertisements in Sweden. More to the point, it explores how the "moderation" regulation in the Swedish Gambling Act (from 2019), as well as industry principles of non-stereotypical gender advertising, impact on the ways in which gambling ads are multimodally designed and organized. The results show that women are explicitly targeted by using both masculine and feminine semiotic strategies, albeit in a "moderate" way. The male market is addressed using stereotypically masculine framings, but without aggressively masculine or macho-like codes. The analysis further exposes that current regulations only partly cover other potential problems in ad design such as ethnic stereotyping. It is argued that the law's demand for moderation in advertising may backfire as a strategy to protect people from the harmful effects of gambling. This because it promotes moderate narratives and moderate gender representations that mimic ordinary practices, settings and lifestyles that appear highly normalised (and thus risk-free). [ABSTRACT FROM AUTHOR]

The authors argue for urgent government action to address nitrous oxide (N2O) addiction and related harms. Emphasis is given on the importance of treating N2O as a potentially addictive substance to highlight the urgency for additional research and evidence-based regulation and to encourage education about its risks and the accessibility of healthcare. The authors call for research funding to increase knowledge on the addictive potential of N2O and signs and symptoms of N2O use disorder.

Background: The way in which research impact is evaluated and assessed has long been under debate. In recent years the focus is moving away from the use of numerical indicators, towards an emphasis on narratives. The Dutch university medical centres (UMCs) have a long-standing tradition of using bibliometric indicators. Because of the declining interest in indicators alone, this study was designed to repurpose bibliometrics to answer specific strategic questions. In this article we discuss the strategic and policy-based questions, the methodology we used in uncovering relevant information and conclusions we draw from the analyses we performed. The aim of this article is to inform a broader audience about the potential applications of bibliometric information to support a new form of research intelligence.Methods: In this study we used a curated set of publications from the UMCs. We performed different bibliometric analyses and used bibliometric visualization tools to shed light on research focus, open science practices, collaboration, societal impact and scientific impact.Results: The analyses allowed us to visualize and contextualize the research focus of the UMCs as a whole, but also to show specific focus areas of each UMC. The UMCs are active in the full spectrum of biomedical research, and at the same time are very complementary to each other. Furthermore, we were able to show the development of open access of UMC publications over time, to support the national mission. Visualizing collaboration is a powerful way of showing both the international orientation and the regional and national engine function of UMCs in research. We were able to assess societal impact by looking at the different channels in which publications find their way to societally relevant sources such as news media, policy documents and guidelines. Finally, we assessed scientific impact and put this into an international perspective.Conclusions: Research intelligence is able to transform bibliometric information by interpretation and annotation into highly relevant insights that can be used for several different strategic purposes and for research impact assessment in general. [ABSTRACT FROM AUTHOR]

Objectives: A high incidence of delirium has been reported in older patients with Coronavirus disease 2019 (COVID-19). We aimed to identify determinants of delirium, including the Clinical Frailty Scale, in hospitalized older patients with COVID-19. Furthermore, we aimed to study the association of delirium independent of frailty with in-hospital outcomes in older COVID-19 patients.Methods: This study was performed within the framework of the multi-center COVID-OLD cohort study and included patients aged ≥60 years who were admitted to the general ward because of COVID-19 in the Netherlands between February and May 2020. Data were collected on demographics, co-morbidity, disease severity, and geriatric parameters. Prevalence of delirium during hospital admission was recorded based on delirium screening using the Delirium Observation Screening Scale (DOSS) which was scored three times daily. A DOSS score ≥3 was followed by a delirium assessment by the ward physician In-hospital outcomes included length of stay, discharge destination, and mortality.Results: A total of 412 patients were included (median age 76, 58% male). Delirium was present in 82 patients. In multivariable analysis, previous episode of delirium (Odds ratio [OR] 8.9 [95% CI 2.3-33.6] p = 0.001), and pre-existent memory problems (OR 7.6 [95% CI 3.1-22.5] p < 0.001) were associated with increased delirium risk. Clinical Frailty Scale was associated with increased delirium risk (OR 1.63 [95%CI 1.40-1.90] p < 0.001) in univariable analysis, but not in multivariable analysis. Patients who developed delirium had a shorter symptom duration and lower levels of C-reactive protein upon presentation, whereas vital parameters did not differ. Patients who developed a delirium had a longer hospital stay and were more often discharged to a nursing home. Delirium was associated with mortality (OR 2.84 [95% CI1.71-4.72] p < 0.001), but not in multivariable analyses.Conclusions: A previous delirium and pre-existent memory problems were associated with delirium risk in COVID-19. Delirium was not an independent predictor of mortality after adjustment for frailty. [ABSTRACT FROM AUTHOR]

Introduction/aims: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset, progressive muscle disease. Quantitative muscle ultrasound (QMUS) assesses structural changes in muscles and is a sensitive biomarker in neuromuscular disorders. Our aim of this study was to determine whether QMUS can detect muscle pathology and can be used as longitudinal imaging biomarker in OPMD.Methods: Genetically confirmed OPMD patients, recruited by their treating physicians or from the national neuromuscular database, were examined twice, 20 months apart, using QMUS of orofacial and limb muscles, and measurements of functional capacity and muscle strength. Absolute echo intensity (AEI) and muscle thickness of all muscles were analyzed and correlated with clinical data.Results: The tongue, deltoid, iliopsoas, rectus femoris, and soleus muscles showed increased AEI at baseline compared with normal values in 43 OPMD patients, with the rectus femoris being most often affected (51%).The AEI and muscle thickness of 9 of 11 muscles correlated significantly with the motor function measure, 10-step stair test, swallowing capacity, dynamometry, Medical Research Council grade, tongue strength, and bite force (r = 0.302 to -0.711). Between baseline and follow-up, deterioration in AEI was found for the temporalis, tongue, and deltoid muscles, and decreased muscle thickness was detected for the temporalis, masseter, digastric, tongue, deltoid, iliopsoas, and soleus muscles (P < .05). No relation was found between the change in AEI and repeat length or disease duration.Discussion: QMUS detected muscle pathology and disease progression in OPMD over 20 months. We conclude that QMUS should be considered as a biomarker in treatment trials. [ABSTRACT FROM AUTHOR]

Haploinsufficiency for Endoglin (ENG) and activin A receptor type II-like I (ACVRL1/ALK1) lead to the formation of weak and abnormal vessels in hereditary hemorrhagic telangiectasia (HHT). These cause epistaxis (nosebleeds) and/or gastrointestinal blood loss. In vitro in cultured endothelial cells, tacrolimus has been shown to increase ENG and ALK1 expression. It is, therefore, a potential treatment option. We report here a proof-of-concept study in patients with HHT and severe epistaxis and/or gastrointestinal bleeding who were treated daily with orally-administered tacrolimus for twenty weeks. Twenty-five patients with HHT (11 females (44%)) and median age of 59 years were enrolled. Five patients (20%) stopped the trial prematurely-four due to (serious) adverse events ((S)AE). Twenty patients were included in further analyses. Hemoglobin levels increased during tacrolimus treatment from 6.1 (IQR 5.2–6.9) mmol/L at baseline (9.8 g/dL) to 6.7 (6.5–7.1) mmol/L (10.8 g/dL), p = 0.003. The number of blood transfusions over the twenty weeks decreased from a mean of 5.0 (±9.2) to 1.9 (±3.5), p = 0.04. In 64% of the patients, at least one AE occurred. Oral tacrolimus, thus, significantly increased hemoglobin levels and decreased blood transfusion needs, epistaxis and/or gastrointestinal bleeding in patients with HHT. However, side-effects were common. Further investigation of the potential therapeutic benefit is justified by the outcome of the study. [ABSTRACT FROM AUTHOR]

Western blotting is a standard laboratory method used to detect proteins and assess their expression levels. Unfortunately, poor western blot image display practices and a lack of detailed methods reporting can limit a reader's ability to evaluate or reproduce western blot results. While several groups have studied the prevalence of image manipulation or provided recommendations for improving western blotting, data on the prevalence of common publication practices are scarce. We systematically examined 551 articles published in the top 25% of journals in neurosciences (n = 151) and cell biology (n = 400) that contained western blot images, focusing on practices that may omit important information. Our data show that most published western blots are cropped and blot source data are not made available to readers in the supplement. Publishing blots with visible molecular weight markers is rare, and many blots additionally lack molecular weight labels. Western blot methods sections often lack information on the amount of protein loaded on the gel, blocking steps, and antibody labeling protocol. Important antibody identifiers like company or supplier, catalog number, or RRID were omitted frequently for primary antibodies and regularly for secondary antibodies. We present detailed descriptions and visual examples to help scientists, peer reviewers, and editors to publish more informative western blot figures and methods. Additional resources include a toolbox to help scientists produce more reproducible western blot data, teaching slides in English and Spanish, and an antibody reporting template. A systematic assessment of more than 500 articles reveals that western blot figures and methods often omit essential details. The study also provides a collection of recommendations to help scientists avoid common problems, while making their western blot figures and methods more informative, transparent and reproducible. [ABSTRACT FROM AUTHOR]

Is irrational risk-avoiding behavior related to news media's heightened attention for the negative and exceptional? Based on the theoretical approaches of mediatization and cultivation, it is hypothesized how news media can present an overly negative and biased reality that can have a severe impact on society. Focusing on the case of travel accidents, we argue that a disproportional increase in news attention for low-probability high-consequence aviation accidents can distort audiences' risk perceptions such that driving is inaccurately perceived as a safer transportation alternative to flying, with potentially harmful consequences. This study accordingly documents results from time-series analyses (1996–2017) on US media attention for aviation and road accidents related to real-world data on travel behavior and fatal accidents. The over-time patterns expose how news media follow their own mediatized logic and reality: Negative incidents—i.e. both aviation and road accidents—become more prominent in the news over time, rather than accurately reflecting real-world trends. Next, since air travel is statistically the safest transportation mode, disproportionate attention for aviation accidents is argued to especially create a problematic distorted worldview among audiences. Accordingly, findings show how more media attention for aviation accidents is related to relatively more road traffic and more fatal road accidents in the subsequent months. We conclude that the media's systematic overrepresentation of rare aviation accidents can overshadow the more substantial risk of (long-distance) driving. This paper illustrates how a distorted media reality can potentially result in severe consequences in light of audiences' ill-informed fear perceptions and irrational risk-avoiding behavior. [ABSTRACT FROM AUTHOR]

Summary: A 2‐month‐old Warmblood colt presented with recurrent colic and regurgitation. Gastroscopy, performed on several occasions, and barium‐contrast radiography revealed severe squamous gastric ulceration and stenosis at the level of the margo plicatus. Treatment with omeprazole reduced the extent and severity of the gastric ulcers but did not affect the stenosis. The foal was euthanised because of a poor prognosis, and post‐mortem examination confirmed the clinical diagnosis. Severe squamous gastric ulceration, granulation tissue formation and cicatrisation of deep gastric lesions were considered to have caused the stenosis. Gastroduodenal outflow obstruction is a recognised disorder in foals, but stenosis at the level of the margo plicatus has not been reported in foals or adult horses. To the authors' knowledge, this is the first case of severe squamous gastric ulceration, complicated by stenosis at the level of the margo plicatus, in a foal. Although rare, gastric stenosis should be considered in foals suffering recurrent colic and regurgitation. [ABSTRACT FROM AUTHOR]

Background: The cause of prolonged postoperative ileus (PPOI) is multifactorial. The influence of preoperative factors on PPOI has been well documented, but little is known about the impact of intraoperative conditions. The aim of this study was to investigate the influence of intraoperative factors on PPOI in patients undergoing colorectal surgery. Methods: The LekCheck study database of the Colorectal Unit at the Royal Adelaide Hospital was analysed. Per patient, over 60 data points were prospectively collected between March 2018 and July 2020. Intraoperative data were collected in theatre during a one‐off snapshot measure. Univariate and multivariable logistic regression analyses were performed. Results: Data of 336 patients were included. The median age was 66 years and 58.3% were male. Ninety‐three patients (27.7%) developed PPOI. Univariate analysis identified the following intraoperative variables as risk‐factors of PPOI: greater volumes of intraoperative IV fluid administration (464 versus 415 mL/h for those without PPOI; p = 0.04), side‐to‐side anastomosis orientation (53.8 versus 41.2%; p = 0.04) and increased perioperative opioid use (6.73 versus 4.11 mg/kg morphine equivalents for patients with and without PPOI, respectively; p = 0.02). Upon multivariable analysis, increased perioperative opioid use remained significant (p = 0.05), as well as the preoperative factors anticoagulation use (p = 0.04) and higher levels of serum total protein (p = 0.02). Conclusion: This study suggests that intraoperative factors may also contribute to the development of PPOI, but this could not be confirmed in the multivariate analysis. Further studies including larger patient numbers will be required to determine the impact of intraoperative conditions on the development of PPOI. [ABSTRACT FROM AUTHOR]

Summary: Extracellular ATP is a purinergic signal with important functions in regulating plant growth and stress‐adaptive responses, including programmed cell death. While signalling events proximate to receptor activation at the plasma membrane have been characterised, downstream protein targets and the mechanism of cell death activation/regulation are unknown.We designed a proteomic screen to identify ATP‐responsive proteins in Arabidopsis cell cultures exposed to mycotoxin stress via fumonisin B1 (FB1) application.Arabidopsis RIBONUCLEASE 1 (RNS1) was identified by the screen, and transgenic plants overexpressing native RNS1 showed greater susceptibility to FB1, while a gene knockout rns1 mutant and antisense RNS1 transgenic plants were resistant to FB1‐induced cell death. Native RNS1 complemented rns1 mutants and restored the cell death response to FB1, while a catalytically inactive version of the ribonuclease could not. The FB1 resistance of salicylic acid (SA)‐depleted nahG‐expressing plants was abolished by transformation with native RNS1, but not the catalytically dead version.The mechanism of FB1‐induced cell death is activation of RNS1‐dependent RNA cleavage, which is blocked by ATP via RNS1 suppression, or enhanced by SA through induction of RNS1 expression. Our study reveals RNS1 as a previously unknown convergence point of ATP and SA signalling in the regulation of stress‐induced cell death. [ABSTRACT FROM AUTHOR]

To investigate the influence of frailty in elderly with severe TBI on mortality and functional outcome. 126 patients with TBI aged 60 years or older and with a presenting Glasgow Coma Scale score of 8 or lower were retrospectively included. To investigate frailty, we used the CSHA Clinical Frailty Scale. The primary outcome measures were mortality, and the secondary outcome measures were Glasgow Outcome Scale Extended (GOSE) at discharge and GOSE at 6 months after trauma. High frailty was a significant predictor for mortality (OR 2.38, p 0.047), if adjusted for the injury severity scale. High frailty was also a significant predictor for poor functional outcome after 6 months (OR 4.35, p 0.03). After 6 months, the GOSE of the low frailty group was significantly higher than in the high frailty group (p 0.019). Also, the improvement of the GOSE was significant in the low frailty group (p 0.007), while in the high frailty group there was no significant improvement of the GOSE (p 0.546) after 6 months. Frailty has a significant impact on outcome in elderly with severe TBI. There is a higher mortality in the frail elderly and there is less recovery after TBI. [ABSTRACT FROM AUTHOR]

The health-related quality of life (HRQoL) among persons living with HIV (PLWHA) who initiate ART during acute HIV infection (AHI) is not well studied. Participants in the SEARCH010/RV254 cohort initiated ART during AHI. They completed the Thai version of the World Health Organisation Quality of Life instrument-BREF (WHOQOL-BREF) and Patient Health Questionnaire-9 (PHQ-9) prior to ART initiation and 24 weeks later. Of 452 participants, 406 (90%) completed the WHOQOL-BREF. The median age was 26 years (IQR 22–31), and 98% were men. All WHOQOL-BREF domains demonstrated good internal consistency (Cronbach's alpha >0.70). Confirmatory factor analysis validated the WHOQOL-BREF model. 90% of Pearson correlations between domain scores and general facet items were >0.50. HRQoL in all domains was worse among those with at least moderately severe depression (PHQ-9 ≥ 10) (p<0.0001), supporting discriminant validity. At 24 weeks, there was an improvement of scores in all domains (physical, psychological, social, and environmental) and general facet items (p<0.0001), and the range of mean domain scores was 14.7–15.6 (SD 2.3–2.8). The majority of participants (58–63%) had improved HRQoL in the physical, psychological and environmental domains. It is concluded that HRQoL improves 6 months after initiation of ART in AHI, suggesting a benefit of early ART initiation. [ABSTRACT FROM AUTHOR]

To ensure the needs of children and families are met for the remainder of the COVID-19 situation and beyond there is a demand for a specific response strategy. This longitudinal study will investigate the impact of COVID-19 on Australian parental and childhood mental health symptoms, particularly OCD symptoms, examining the stability of this relationship over time and the needs and preferences for mental health support in response to child symptoms. A total of 141 parents completed a questionnaire during the lockdown period in Australia (June–September 2020). Thirty-five of them completed a follow-up questionnaire during the post-lockdown period (November 2020–January 2021). The questionnaire assessed COVID-19 experiences/worries/knowledge, child OCD, and child/parental anxiety and depression. Sub-samples of youth were determined based on parent-report of an existing diagnosis of any mental health (n = 24), of OCD (n = 22), or no mental health diagnosis (i.e., healthy, n = 81). Results: Parents reported a significant positive association between increased parental worries regarding COVID-19, and their own as well as their child's mental health symptoms. The current sample of children experienced elevated symptom severity for OCD symptoms during COVID-19. The OCD group reported significant reductions in child OCD symptoms at post-lockdown. The any mental health diagnosed children are at greater risk of developing OCD symptoms and reported strong preferences for increased support as a result. The exploratory nature of this study adds further insight into the impact of the COVID-19 pandemic on child OCD and parent mental health symptoms and the stability of symptoms over time. [ABSTRACT FROM AUTHOR]