Search

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]

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]

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]

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]

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]

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]

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]

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: 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]

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]

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]

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]

We consider the Π -free Deletion problem parameterized by the size of a vertex cover, for a range of graph properties Π. Given an input graph G , this problem asks whether there is a subset of at most k vertices whose removal ensures the resulting graph does not contain a graph from Π as an induced subgraph. We introduce the concept of characterizing a graph property Π by low-rank adjacencies , and use it as the cornerstone of a general kernelization theorem for Π -Free Deletion parameterized by the size of a vertex cover. The resulting framework captures problems such as AT-Free Deletion , Wheel-free Deletion , and Interval Deletion. Moreover, our new framework shows that the vertex-deletion problem to perfect graphs has a polynomial kernel when parameterized by vertex cover, thereby resolving an open question by Fomin et al. (2014) [18]. [ABSTRACT FROM AUTHOR]

Objectives Agreement between real-time and static ultrasonography has not been studied in musculoskeletal diseases. We studied this agreement in inflammatory hand OA. Methods Ultrasonography was performed blinded to clinical information of 30 joints of 75 patients with hand OA, treated with prednisolone in a randomized placebo-controlled double-blind trial. Images were scored real-time at acquisition and stored images were scored static (paired in known chronological order) for inflammatory features and osteophytes (score 0–3). Agreement between methods was studied at joint level with quadratic weighted kappa. At patient level intra-class correlations (ICC) of sum scores and change in sum-scores (delta baseline—week 6) were calculated. Responsiveness of scoring methods was analysed with generalized estimating equations (GEE) with treatment as independent and ultrasonography findings as dependent variable. Results Agreement at baseline was good to excellent at joint level (kappa 0.72–0.88) and moderate to excellent at patient level (ICC 0.58–0.91). Agreement for change in sum scores was poor to fair for synovial thickening and effusion (ICC 0.18 and 0.34, respectively), while excellent for Doppler signal (ICC 0.80). Real-time ultrasonography discriminated between prednisolone and placebo with a mean between-group difference of synovial thickening of −2.5 (95% CI: −4.7, −0.3). Static ultrasonography did not show a decrease in synovial thickening. Conclusion While cross-sectional agreement between real-time and static ultrasonography is good, static ultrasonography measurement of synovial thickening did not show responsiveness to prednisone therapy while real-time ultrasonography did. Therefore, when ultrasonography is used in clinical trials, real-time dynamic scoring should remain the standard for now. [ABSTRACT FROM AUTHOR]

High strain-rate testing of high-density polyethylene is the focus of the present work. This testing is accomplished by two types of experimental testing: uniaxial tensile testing using standard testing technique, and impact testing of a 3D structure with non-trivial geometry. Both the uniaxial tests and the impact tests were evaluated using a material model suited for rate-dependent inelasticity of polymers that has been developed. In the uniaxial tensile tests, a maximum strain-rate of about 28/s was attained. In the impact tests, strain-rates of the order of 100/s and beyond were predicted in the analyses. The impact tests were simulated and analysed by use of finite element simulations. Coupled Eulerian-Lagrangian (CEL) analyses were employed for some of the tests where there was an interaction between the compressed structure and air trapped inside it. Overall, the simulations were able to reproduce the outcome from the experiments well. In particular, the deformation scenarios in the impact tests for different loading situations could be reproduced. • Uniaxial tensile testing of high-density polyethylene at high strain-rates. • Impact testing of 3D high-density polyethylene structure at different impact velocities. • Analysis of impact tests using coupled Eulerian-Lagrangian (CEL) finite element analysis. [ABSTRACT FROM AUTHOR]

Job advertisements hold a wealth of knowledge for the public relations field about complex internal and external organizational dynamics. They reflect enduring social and sectoral cultural proclivities and associated stereotypes about workers. We examine the presence of stereotypical frames in job advertisements from sectors with varying gender and age social group composition. Guided by social categorization framing and the stereotype content model, we operationalize stereotypical warmth- and competence-related frames in candidate sourcing communication. Automated content analysis was conducted on a dataset of online job ad sentences (n = 308,583) from 16,135 job ads. Results indicate warmth-related frames are most observed in ads from female-dominated (vs. male-dominated) sectors and younger-dominated (vs. older-dominated and mixed-age) sectors. Conversely, competence-related frames are most observed in ads from male-dominated (vs. female-dominated and mixed-age) sectors and older-dominated (vs. younger-dominated and mixed-age) sectors. We additionally find candidate gender stereotypes may supersede age stereotypes in hiring contexts. Implications are discussed in light of socialization and structuralist forces and their influence on organizational communication in homogeneous and heterogeneous sectors. • Job advertisements reflect compound occupational dynamics that encode stereotypes of "ideal" candidate in sectoral culture. • Stereotypical warmth-related frames appear more in job advertisements from female- and younger-dominated sectors. • Stereotypical competence-related frames appear more in job advertisements from male- and older-dominated sectors. • Gender stereotypes may supersede age stereotypes in the context of candidate sourcing communication. • Communication in homogeneous sectors exhibits social categorization whereas heterogeneous sectors highligh sectoral demands. [ABSTRACT FROM AUTHOR]

Traditionally, topographic surveying in earth sciences requires high financial investments, elaborate logistics, complicated training of staff and extensive data processing. Recently, off-the-shelf drones with optical sensors already reduced the costs for obtaining a high-resolution dataset of an Earth surface considerably. Nevertheless, costs and complexity associated with topographic surveying are still high. In 2020, Apple Inc. released the iPad Pro 2020 and the iPhone 12 Pro with novel build-in LiDAR sensors. Here we investigate the basic technical capabilities of the LiDAR sensors and we test the application at a coastal cliff in Denmark. The results are compared to state-of-the-art Structure from Motion Multi-View Stereo (SfM MVS) point clouds. The LiDAR sensors create accurate high-resolution models of small objects with a side length > 10 cm with an absolute accuracy of ± 1 cm. 3D models with the dimensions of up to 130 × 15 × 10 m of a coastal cliff with an absolute accuracy of ± 10 cm are compiled. Overall, the versatility in handling outweighs the range limitations, making the Apple LiDAR devices cost-effective alternatives to established techniques in remote sensing with possible fields of application for a wide range of geo-scientific areas and teaching. [ABSTRACT FROM AUTHOR]

Objective.: To review the new ultra-rapid-acting insulin analogs and describe the benefits and limitations compared with other bolus insulins. Summary.: The options for bolus insulins, which are usually taken at mealtime or for correction of hyperglycemia, are expanding, with recent approvals of faster-acting insulin aspart and insulin lispro-aabc. These new-generation insulins contain additives that enhance absorption and accelerate onset of action. Clinical studies demonstrate that, although these insulins are faster acting, their efficacy for A1C lowering and safety in terms of hypoglycemia risk are similar to those of other available bolus insulin options such as rapid-acting insulin analogs. However, their use resulted in significant reductions in 1- and 2-hour postprandial glucose levels. Conclusion.: Novel ultra-rapid-acting insulins provide additional bolus insulin options, and their quick onset of action provides additional dosing flexibility for people with diabetes. Given their comparable efficacy and safety compared to other quick-acting insulins, health care providers should engage in shared decision-making with patients and their caregivers regarding possible use of ultra-rapid-acting insulin, taking into account their preferences, individualized considerations, and insurance formulary coverage. These new insulin formulations may be a suitable option for people with diabetes who are not able to achieve postprandial glycemic targets with other bolus insulins. [ABSTRACT FROM AUTHOR]

Glucocorticoid (GC)‐induced osteoporosis is a widespread health problem that is accompanied with increased fracture risk. Detrimental effects of anti‐inflammatory GC therapy on bone have been ascribed to the excess in GC exposure, but it is unknown whether there is also a role for disruption of the endogenous GC rhythm that is inherent to GC therapy. To investigate this, we implanted female C57Bl/6J mice with slow‐release corticosterone (CORT) pellets to blunt the rhythm in CORT levels without inducing hypercortisolism. Flattening of CORT rhythm reduced cortical and trabecular bone volume and thickness, whilst bone structure was maintained in mice injected with supraphysiologic CORT at the time of their endogenous GC peak. Mechanistically, mice with a flattened CORT rhythm showed disrupted circadian gene expression patterns in bone, along with changes in circulating bone turnover markers indicative of a negative balance in bone remodelling. Indeed, double calcein labelling of bone in vivo revealed a reduced bone formation in mice with a flattened CORT rhythm. Collectively, these perturbations in bone turnover and structure decreased bone strength and stiffness, as determined by mechanical testing. In conclusion, we demonstrate for the first time that flattening of the GC rhythm disrupts the circadian clock in bone and results in an osteoporotic phenotype in mice. Our findings indicate that at least part of the fracture risk associated with GC therapy may be the consequence of a disturbed GC rhythm, rather than excess GC exposure alone, and that a dampened GC rhythm may contribute to the age‐related risk of osteoporosis. [ABSTRACT FROM AUTHOR]

The article discusses the Supreme Court case of Data Protection Commissioner versus Facebook Ireland, Limited. The goal of privacy activist Maximillian Schrems was to protect the European Union data users' information privacy. The Court of Justice of the European Union adopted principles that would fragment the European Union's internet away from the global, open internet, but governments of the Industrial World are not welcome.

Background: Endometrial cancer (EC) risk in BReast CAncer gene 1/2 (BRCA1/2) mutation carriers is uncertain; therefore, we assessed this in a large Dutch nationwide cohort study.Methods: We selected 5980 BRCA1/2 (3788 BRCA1, 2151 gBRCA2, 41 both BRCA1/BRCA2) and 8451 non-BRCA1/2 mutation carriers from the Hereditary Breast and Ovarian cancer study, the Netherlands cohort. Follow-up started at the date of the nationwide Dutch Pathology Registry coverage (January 1, 1989) or at the age of 25 years (whichever came last) and ended at date of EC diagnosis, last follow-up, or death (whichever came first). EC risk in BRCA1/2 mutation carriers was compared with 1) the general population, estimating standardized incidence ratios (SIRs) based on Dutch population-based incidence rates; and 2) non-BRCA1/2 mutation carriers, using Cox-regression analyses, expressed as hazard ratio (HR). Statistical tests were 2-sided.Results: Fifty-eight BRCA1/2 and 33 non-BRCA1/2 mutation carriers developed EC over 119 296 and 160 841 person-years, respectively (SIR = 2.83, 95% confidence interval [CI] = 2.18 to 3.65; and HR = 2.37, 95% CI = 1.53 to 3.69, respectively). gBRCA1 mutation carriers showed increased risks for EC overall (SIR = 3.51, 95% CI = 2.61 to 4.72; HR = 2.91, 95% CI = 1.83 to 4.66), serous-like EC (SIR = 12.64, 95% CI = 7.62 to 20.96; HR = 10.48, 95% CI = 2.95 to 37.20), endometrioid EC (SIR = 2.63, 95% CI = 1.80 to 3.83; HR = 2.01, 95% CI = 1.18 to 3.45), and TP53-mutated EC (HR = 15.71, 95% CI = 4.62 to 53.40). For BRCA2 mutation carriers, overall (SIR = 1.70, 95% CI = 1.01 to 2.87) and serous-like EC risks (SIR = 5.11, 95% CI = 1.92 to 13.63) were increased compared with the general population. Absolute risks by 75 years remained low (overall EC = 3.0%; serous-like EC = 1.1%).Conclusions: BRCA1/2 mutation carriers have a two- to threefold increased risk for EC, with highest risk observed for the rare subgroups of serous-like and p53-abnormal EC in BRCA1 mutation carriers. [ABSTRACT FROM AUTHOR]

Summary: We have recently characterised NET2A as a pollen‐specific actin‐binding protein that binds F‐actin at the plasma membrane of growing pollen tubes. However, the role of NET2 proteins in pollen development and fertilisation have yet to be elucidated.To further characterise the role of Arabidopsis NET2 proteins in pollen development and fertilisation, we analysed the subcellular localisation of NET2A over the course of pollen grain development and investigated the role of the NET2 family using net2 loss‐of‐function mutants.We observed NET2A to localise to the F‐actin cytoskeleton in developing pollen grains as it underwent striking structural reorganisations at specific stages of development and during germination and pollen tube growth. Furthermore, net2 loss‐of‐function mutants exhibited striking morphological defects in the early stages of pollen tube growth, arising from frequent changes to pollen tube growth trajectory. We observed defects in the cortical actin cytoskeleton and actin‐driven subcellular processes in net2 mutant pollen tubes.We demonstrate that NET2 proteins are essential for normal actin‐driven pollen development highlighting an important role for the NET2 family members in regulating pollen tube growth during fertilisation. [ABSTRACT FROM AUTHOR]

Tropical corals and Amphistegina, an example genus of symbiont-bearing larger benthic foraminifera, are presently living close to their thermal bleaching thresholds. As such, these essential reef-building organisms are vulnerable to the future prospect of more frequent sea surface temperature (SST) extremes. Exploring the earth's paleo-climatic record, including interglacials warmer than present, may provide insights into future oceanographic conditions. We analyse foraminiferal shell geochemical compositions, from Recent surface sediments and Marine Isotope stage (MIS) 9e and MIS11c aged sediments, from the International Ocean Discovery Program Expedition 359 Site U1467 drilled in the Inner Sea of the Maldives. We illustrate through traditional (pooled) geochemical analysis (δ18O, Mg/Ca) that tropical temperatures were indeed marginally warmer during MIS9e and MIS11c in comparison to the modern ocean. Individual foraminiferal analysis (IFA) from the Recent (representing the last few hundred years) and MIS9e samples shows SSTs occasionally breached the coral bleaching threshold similarly to the modern-day. Significantly, the number of transgressions was four times higher during MIS11c, a recognised analogue for a warmer modern world. This new knowledge and novel IFA insight and application is invaluable given thermal stress is already obvious today with an increasing number of bleaching events over the last few decades. [ABSTRACT FROM AUTHOR]

Cue reactivity is an important biomarker of cannabis use disorder (CUD). Despite high rates of cigarette and cannabis co‐use, its role in cannabis cue reactivity remains unclear. Using a visual functional magnetic resonance imaging cue reactivity paradigm, we investigated interactive effects of cannabis and cigarette use on cannabis cue relative to cigarette and neutral cue reactivity in a priori regions of interest—the amygdala, striatum, anterior cingulate cortex (ACC), ventral tegmental area (VTA), and orbitofrontal cortex—and a whole‐brain analysis. In our sample of cannabis users and controls closely matched on cigarette use, significant interactions between cannabis and cigarette use status emerged in the amygdala, striatum, ACC, frontal pole, and inferior frontal gyrus. Cannabis‐only users showed heightened cue reactivity in the amygdala compared with nonusing controls. Co‐users did not show heightened cue reactivity compared with cigarette smoking controls, although cue‐induced VTA activity was positively correlated with grams per week of cannabis. Cigarette smoking controls showed unexpectedly heightened cue reactivity compared to co‐users and nonsmoking controls. These findings and the high prevalence of cannabis and cigarette co‐use underscore the importance of considering cigarette smoking status when investigating the role of cue reactivity in heavy cannabis use. [ABSTRACT FROM AUTHOR]

Accurately calculating the annual yield of floating PV (FPV) systems necessitates incorporating appropriate FPV-specific heat loss coefficients into the calculation, including both wind-dependent and wind-independent factors. The thermal behavior of several FPV systems has been investigated within this study, through the analysis of heat loss coefficients across various system sizes and configurations. Over a one-year period, data were collected from two measurement sites with three distinct systems: two ~50 kWp demonstrator-scale setups of Solarisfloat (azimuthal tracking) and Solar Float (East-West orientation) and a 2 MWp commercial-scale East–West system by Groenleven. The Solarisfloat demonstrator revealed a wind-dependent heat loss coefficient of 3.2 W/m3Ks. In comparison, the Solar Float demonstrator system displayed elevated wind-dependent heat loss coefficients, measuring 4.0 W/m3Ks for the east-facing module and 5.1 W/m3Ks for the west-facing module. The Groenleven system, which shares design similarities with Solar Float, showed lower wind-dependent heat loss coefficients of 2.7 W/m3Ks for the east-facing module and 2.8 W/m3Ks for the west-facing module. A notable discrepancy in the wind-dependent coefficients, particularly evident under a north wind direction, indicates a more efficient convective cooling effect by the wind on the demonstrator scale system of Solar Float. This could possibly be attributed to improved wind flow beneath its PV modules, setting it apart from the Groenleven system. Additionally, a thermal model founded on a 'balance-of-energy' methodology, integrating water temperature as a variable was introduced. The heat loss coefficient, dependent on the surface water temperature, fluctuated around zero, depending on whether the water temperature surpassed or fell below the ambient air temperature. It can be concluded that it is not of added value to introduce this floating specific heat loss coefficient parameter, as this parameter can be integrated in the wind speed independent Uc parameter. [ABSTRACT FROM AUTHOR]

Graph-deletion problems involve deleting a small number of vertices so that the resulting graph belong to a given hereditary graph class. We initiate a study of a natural variation of the problem of deletion to scattered graph classes. We want to delete at most k vertices so that each connected component of the resulting graph belongs to one of the constant number of graph classes. As our main result, we show that this problem is non-uniformly fixed-parameter tractable (FPT) when the deletion problem corresponding to each of the constant number of graph classes is known to be FPT and the properties that a graph belongs to these classes are expressible in Counting Monodic Second Order (CMSO) logic. While this is shown using some black box theorems in parameterized complexity, we give a faster FPT algorithm when each of the graph classes has a finite forbidden set. [ABSTRACT FROM AUTHOR]

Polar polythiophenes with oligoethylene glycol side chains are exceedingly soft materials. A low glass transition temperature and low degree of crystallinity prevents their use as a bulk material. The synthesis of a copolymer comprising 1) soft polythiophene blocks with tetraethylene glycol side chains, and 2) hard urethane segments is reported. The molecular design is contrary to that of other semiconductor‐insulator copolymers, which typically combine a soft nonconjugated spacer with hard conjugated segments. Copolymerization of polar polythiophenes and urethane segments results in a ductile material that can be used as a free‐standing solid. The copolymer displays a storage modulus of 25 MPa at room temperature, elongation at break of 95%, and a reduced degree of swelling due to hydrogen bonding. Both chemical doping and electrochemical oxidation reveal that the introduction of urethane segments does not unduly reduce the hole charge‐carrier mobility and ability to take up charge. Further, stable operation is observed when the copolymer is used as the active layer of organic electrochemical transistors. [ABSTRACT FROM AUTHOR]

An Eulerian thermomechanical elastic–viscoplastic model with isotropic and directional hardening is used to analyse the residual mechanical state resulting from the arc welding of a multi-pass weld. Details of the weld test plate, weld filler material, and numerical implementation of the model are provided, including integration algorithms and consistent tangent modulus. For the computational welding mechanics analyses, the austenitic ASME stainless steel grade 316L was considered so that no phase transformations of solid states needed to be considered. The maximum residual stresses were found to be about 500–600 MPa, which is of the order of the yield stress of the base material. Variations in the heat input and the resulting weld cooling time had a significant influence both on the residual stress state and on the resulting geometry of the weld. The predicted stress levels were compared to the experimental results. Overall, the proposed Eulerian framework seems to be a promising tool for analysing melting/solidification processes and residual mechanical states. [ABSTRACT FROM AUTHOR]

Abnormal vasculature is a key feature of hereditary hemorrhagic telangiectasia (HHT) and can also present in the nail fold capillary beds. However, the exact prevalence and the clinical diagnostic value in HHT are still largely unknown. The nail fold can be easily and noninvasively inspected with a capillary microscope. We therefore retrospectively assessed the prevalence and diagnostic value of abnormal nail fold capillaries in all patients who were screened between January 2000 and July 2017 for the presence of HHT and underwent capillary microscopy in St Antonius Hospital, The Netherlands. Capillary microscopy results and clinical characteristics were extracted from medical files and the prevalence of abnormal nail fold capillaries was calculated and the diagnostic value of the Curaçao criteria with and without capillary microscopy results was assessed. Of the 1761 individuals screened, 923 (52%) were diagnosed with a clinical and/or genetic HHT diagnosis. In these patients, capillary microscopy was normal in 23% (n = 218), enlarged loops were seen in 11% (n = 99), and giant loops in 66% (n = 606). The sensitivity and specificity of the Curaçao criteria for the diagnosis of HHT without capillary microscopy results were 96% and 90%, respectively. The addition of the presence of giant loops to the Curaçao criteria led to a small increase in sensitivity to 97% without affecting the specificity. In conclusion, the prevalence of nail fold abnormalities in patients with HHT is high. Capillary microscopy can be a useful, easy, and noninvasive diagnostic tool in HHT. [ABSTRACT FROM AUTHOR]

The corallivorous Crown-of-Thorns Starfish (CoTS, Acanthaster spp.) has been linked with the widespread loss of scleractinian coral cover on Indo-Pacific reefs during periodic population outbreaks. Here, we re-examine CoTS consumption by coral reef fish species by using new DNA technologies to detect Pacific Crown-of-Thorns Starfish (Acanthaster cf. solaris) in fish faecal and gut content samples. CoTS DNA was detected in samples from 18 different coral reef fish species collected on reefs at various stages of CoTS outbreaks in the Great Barrier Reef Marine Park, nine of which had not been previously reported to feed on CoTS. A comprehensive set of negative and positive control samples confirmed that our collection, processing and analysis procedures were robust, although food web transfer of CoTS DNA cannot be ruled out for some fish species. Our results, combined with the (i) presence of CoTS spines in some samples, (ii) reported predation on CoTS gametes, larvae and settled individuals, and (iii) known diet information for fish species examined, strongly indicate that direct fish predation on CoTS may well be more common than is currently appreciated. We provide recommendations for specific management approaches to enhance predation on CoTS by coral reef fishes, and to support the mitigation of CoTS outbreaks and reverse declines in hard coral cover. [ABSTRACT FROM AUTHOR]

Objectives To evaluate self-reported and assessor-reported joint counts for pain and their value in measuring pain and joint activity in hand OA patients. Methods A total of 524 patients marked painful joints on hand diagrams. Nurses assessed tenderness upon palpation. Pain was measured with a visual analogue scale pain and the Australian/Canadian hand OA index subscale pain. Synovitis and bone marrow lesions in right hand distal/proximal interphalangeal joints on MRI served as measure of joint activity. Agreement was assessed on the patient (intraclass correlation coefficient, Bland–Altman plot) and joint level (percentage absolute agreement). Correlations with measures of pain and joint activity were analysed, and joint level associations with synovitis/bone marrow lesions were calculated. Results Self-reported painful joint count (median 8, interquartile range 4–13) was consistently higher than assessor-reported tender joint count (3, 1–7). Agreement between patients and nurses on overall scores was low. Percentage absolute agreement on the joint level was 61–89%. Joint counts correlated similarly but weakly with measures of pain and joint activity (r = 0.14–0.38). On the joint level, assessor-reported tenderness was more strongly associated with synovitis/bone marrow lesions than self-reported pain. Conclusion In hand OA, self- and assessor-reported joint counts cannot be used interchangeably, and measure other pain aspects than questionnaires. Assessor-reported tenderness was most closely related to MRI-defined joint activity. [ABSTRACT FROM AUTHOR]

Isoflavones and isoflavandiols have shown many health benefits, such as reducing cardiovascular disease, cancer, age-related disease, and osteoporosis. However, to investigate the relationships between consumption of isoflavones and their health benefits, it is important to be able to accurately quantify exposure in the large numbers of samples typically produced in association studies (i.e., several thousands). Current methods rely on solid-phase extraction protocols for sample cleanup, resulting in protracted extraction and analysis times. Here, we describe a fast and easy sample preparation method of human urine samples for subsequent quantification of daidzein, genistein (isoflavones), and equol (isoflavandiol) using LC-MS/MS. Sample preparation involves only the addition of dimethylformamide (DMF) and formic acid (FA) after enzymatic hydrolysis of their metabolites by a β-glucuronidase and sulfatase mixture. The method was validated by precision, linearity, accuracy, recoveries, limit of detection (LOD), and limit of quantification (LOQ). Linear calibration curves have been shown by daidzein, genistein, and equol. The correlation coefficients values are r2 > 0.99 for daidzein, genistein, and equol. LOD for daidzein and genistein was 1 ng/ml and equol was 2 ng/ml. Recoveries were >90%, and the relative standard deviation for intraday (<10%) and interday (≤20% over 10 days) was good. This method is suitable for quantification of isoflavones and the microbial metabolite equol in human urine and is particularly useful where large numbers of samples require analysis. [ABSTRACT FROM AUTHOR]

Aim: To assess the concurrent validity and discriminative ability of total, gross and fine motor (TM, GM and FM) scores of Dutch performance-based motor tests, the Baecke-Fassaert Motor Test (BFMT) and the 8- and 4-Skills Scan (SkSc) with the Movement Assessment Battery (MABC) for children at age 5. Method: 116 Dutch children (40.3% boys) were included. Spearman's rho correlations and area under the curves (AUC) were assessed. Results: Correlations between the TM scores of the tests were strong (absolute values from 0.58 to.65); the correlations between the GM scores and the FM scores between and within tests were weaker (absolute values from 0.30 to 0.45). Related to the cut-off (15th percentile) of the MABC, the AUC of the BFMT, 8- and 4-SkSc, the AUC was 0.853 (95% CI: 0.757–0.949), 0.905 (95% CI: 0.837–0.972) and 0.844 (95% CI: 0.730–0.957), respectively. At optimal cut-offs, the sensitivity and specificity of the BFMT, the 8- and 4-SkSc were 78.6 and 78.4%, 92.2 and 73.2%, 78.6 and 76.3%, respectively. Conclusion: All tests had a reasonably high discriminative ability, but validation with the MABC-2 and adaptations are needed to meet the requirements for screening (i.e. sensitivity ≥80% and specificity ≥90%). The relatively weak correlation between GM and FM scores implies that tests should be normalized and validated for GM and FM ability, separately. [ABSTRACT FROM AUTHOR]

Within the world’s oceans, regionally distinct ecological niches develop due to differences in water temperature, nutrients, food availability, predation and light intensity. This results in differences in the vertical dispersion of planktonic foraminifera on the global scale. Understanding the controls on these modern-day distributions is important when using these organisms for paleoceanographic reconstructions. As such, this study constrains modern depth habitats for the northern equatorial Indian Ocean, for 14 planktonic foraminiferal species (G. ruber, G. elongatus, G. pyramidalis, G. rubescens, T. sacculifer, G. siphonifera, G. glutinata, N. dutertrei, G. bulloides, G. ungulata, P. obliquiloculata, G. menardii, G. hexagonus, G. scitula) using stable isotopic signatures (δ18O and δ13C) and Mg/Ca ratios. We evaluate two aspects of inferred depth habitats: (1) the significance of the apparent calcification depth (ACD) calculation method/equations and (2) regional species-specific ACD controls. Through a comparison with five global, (sub)tropical studies we found the choice of applied equation and δ18Osw significant and an important consideration when comparing with the published literature. The ACDs of the surface mixed layer and thermocline species show a tight clustering between 73–109 m water depth coinciding with the deep chlorophyll maximum (DCM). Furthermore, the ACDs for the sub-thermocline species are positioned relative to secondary peaks in the local primary production. We surmise that food source plays a key role in the relative living depths for the majority of the investigated planktonic foraminifera within this oligotrophic environment of the Maldives and elsewhere in the tropical oceans. [ABSTRACT FROM AUTHOR]

It is well known that patients with EC after at least 5 years tamoxifen use are at increased EC mortality risk compared with never users (hazard ratio = 1.59, 95% confidence interval = 1.13 to 2.25) ([3]). In our opinion, we should start today to consider EC and especially p53-abnormal EC and serous-like EC part of the hereditary breast and ovarian cancer syndrome caused by I gBRCA1/2 i mutations. But most of all, we are pleased with their support of our statement that, given the increased risks of I gBRCA1/2 i mutation carriers to develop p53-abnormal (11- to 12-fold) and serous-like endometrial cancer (8- to 10-fold) presented in our article, endometrial cancer (EC) and especially p53-abnormal and serous-like EC should be considered part of the hereditary breast and ovarian cancer syndrome caused by a I gBRCA1/2 i mutation. [Extracted from the article]

• To make simulators feel real, perceived simulator and real motion should match. • We tested whether speed estimated in km/h could be a valid metric for that purpose. • Not finding differences between real, virtual and no view, disqualifies the metric. • Results may be understood by discriminating perception from cognition. Car handling, and hence, safety, is affected by the way we estimate speed. Speed, however, is often underestimated in degraded visual environments, including virtual environments such as driving simulators. In simulators the visual and physical motion are typically incongruent as limited by quality and amplitude, respectively, which may cause a negative transfer of training. To improve the (training) quality of simulators and make them feel more real, it would be helpful to fill a knowledge gap on in-car speed perception as affected by real and virtual views, within a single group of subjects. We did so by testing whether estimations of speed in terms of km/h could be a valid metric for that purpose. We therefore exposed 17 subjects, seated as passengers in the front of a car on a straight road to four experimental conditions: (1) driving with a real out-the-window view, (2) driving with a live video view, (3) standing still watching pre-recorded video's, and (4) driving with eyes closed. Field-of-view was made equal in all conditions. Speeds tested ranged between 20 and 60 km/h. On average, speed was estimated 5 km/h less than actual, while we did not find a statistically significant difference between the four conditions tested. These results seem to contradict previous observations on motion perception, in particular in simulators, that have been ascribed to the quality of the visuals used. This finding may yet be explained by the assumption that speed estimations in terms of km/h are dominated by (conscious) cognitive processes, while visual-vestibular coherence between visual and physical motion, is dominated by (unconscious) sensorial driven perceptual processes. This disqualifies perceived speed as a valid metric for studying motion perception related to the optimisation of simulators. [ABSTRACT FROM AUTHOR]

Demographic events such as the birth and death of organisms are ubiquitous in nature. Disentangling the processes that underlie the demographic dynamics of species is fundamental to understanding how biodiversity is organized and will be re‐organized at multiple scales.To provide new insights on multispecies demographic dynamics, I designed the present study to focus on local and biogeographic influences on mortality and recruitment rates for tree populations in forest biomes throughout the Japanese archipelago.Most populations exhibited mortality that fell within the 95% confidence intervals of a neutral model (i.e. the expectation of demographic stochasticity). However, there were also important determinants that make population dynamics to deviate from the neutral expectation. Interspecific niche differentiation was important to reduce the mortality rate, regardless of the local rarity or ubiquity of a species. Although intraspecific aggregation that caused density‐dependent mortality was only significant for locally abundant species, the degree of isolation from a species' central or optimal range determined mortality only for locally rare species. These differences between rare and common species provide important empirical quantification of aspects of population dynamics that have been less accounted for in ecology and biogeography studies.Synthesis. Unifying different theories such as those rooted in local‐scale community ecology and macro‐scale biogeography is important. At this juncture, this study emphasizes that disentangling the interactive roles of demographic stochasticity and determinism that operate at different scales would be a clue to advance the field of ecology both in theory and practice. [ABSTRACT FROM AUTHOR]

Objective: To assess which factors, including maternal, lifestyle, pregnancy- and delivery-related, fetal and neonatal factors adjusted for socio-economic status, are related to emotional and behavioral problems in moderately-late preterm born children (MLPs; gestational age 32.0–35.9 weeks) at 4 years of age. MLPs are at greater risk of emotional and behavioral problems than full-term born children. Especially for MLPs, knowledge about factors that increase or decrease the risk of emotional and behavioral problems is scarce. Design and setting: We assessed emotional and behavioral problems in 809 MLPs between ages 41 and 49 months from the prospective community-based Longitudinal Preterm Outcome Project (LOLLIPOP), using the parent-reported Child Behavior Checklist (CBCL). We collected potential risk factors from hospital records and parental questionnaires. Univariable and multiple logistic regression analyses were applied. Main outcome measures: (Sub)clinical CBCL scores. Results: Perinatal infection increased the risk of CBCL total problem scores with an OR 2.22 (p<0.01). Perinatal infection, maternal smoking, and male gender increased the risk of CBCL externalizing problem scores with ORs between 1.64 and 2.46 (all p<0.05). Multiple birth decreased the risk of CBCL internalizing problem scores with an OR 0.63 (p<0.05). Conclusions: Risk factors for behavioral problems in MLPs are male gender, perinatal infection and maternal smoking, the latter two being potentially modifiable. Multiple birth is a protective factor for emotional problems in MLPs. These results suggest potential factors for targeting preventive intervention in MLPs, comprising the large majority of all preterm born children. [ABSTRACT FROM AUTHOR]

Massive automatic comparison of languages in parallel corpora will greatly speed up and enhance comparative syntactic research. Automatically extracting and mining syntactic differences from parallel corpora requires a pre-processing step that filters out sentence pairs that cannot be compared syntactically, for example because they involve "free" translations. In this paper we explore four possible filters: the Damerau-Levenshtein distance between POS-tags, the sentence-length ratio, the graph-edit distance between dependency parses, and a combination of the three in a logistic regression model. Results suggest that the dependency-parse filter is the most stable throughout language pairs, while the combination filter achieves the best results. [ABSTRACT FROM AUTHOR]

Abstract The liquid-liquid extraction of a sulfur-nitrogen compound using deep eutectic solvents (DESs) was studied for the first time in this work. Benzothiazole (which contains both nitrogen and sulfur) and thiophene (which only contains sulfur) were separated from n- heptane using two tetrahexylammonium bromide-based DESs. Solubility data for benzothiazole and thiophene in the DESs and the DESs' constituents were determined at 298 K and atmospheric pressure. Subsequently, pseudo-ternary LLE data for the four systems { n -heptane + benzothiazole/thiophene + DES 1/DES 2} were determined at atmospheric pressure and a temperature of 298 K. The consideration of a pseudo-ternary system was validated showing that none of the DES′ constituents appears in the raffinate phase’ in the abstract. Both benzothiazole and thiophene were selectively extracted from their mixtures with n -heptane, but benzothiazole showed even higher affinity towards both DESs than thiophene due to the presence of nitrogen in benzothiazole. From the results derived from the experimental data, the selectivities and distribution ratios of benzothiazole and thiophene were calculated. These calculated values were able to show the potency of the DESs for both desulfurization and denitrogenation. In order to validate the experimental data, the equilibrium data were correlated with the NRTL model using ASPEN Plus. The modeled results showed a strong correlation with the experimental results. Graphical abstract Image 1 Highlights • Deep eutectic solvents (DESs) were used as extractive denitrogenation and desulfurization agents. • LLE data of { n -heptane + benzothiazole/thiophene + DES1/2} were experimentally determined. • Distribution ratios and selectivities were calculated and evaluated. • Experimental LLE data were successfully correlated using the NRTL model. [ABSTRACT FROM AUTHOR]

Operators and passengers need to adjust their plans in cases of large-scale disruptions in railway networks. Where most previous research has focused on the operators, this paper studies the combined support of both in a system where passengers have free route choice. In cases of disruption, passengers receive route advice, which they are not required to follow: passengers' route choice depends on the route advice and the timetable information available to them. Simultaneous to providing advice, rolling stock is rescheduled to accommodate the anticipated passenger demand. The duration of the disruption is uncertain, and passenger flows arise from a complex interaction between the passengers' route choices and the seat capacity allocated to the trains. We present an optimization-based algorithm that aims to minimize passenger inconvenience through provision of route advice and rolling stock rescheduling, where the advice optimization and rolling stock rescheduling modules are supported by a passenger simulation model. The algorithm aims to include and evaluate solutions under realistic passenger behavior assumptions. Our computational tests on realistic instances of Netherlands Railways indicate that the addition of the travel advice effectively improves the service quality to the passengers more than only rescheduling rolling stock, even when not all passengers follow the advice. The online appendix is available at https://doi.org/10.1287/trsc.2017.0759. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of TNF inhibitors (TNFis) on incidental and progressive hand OA in recent-onset RA patients after a 10 year follow-up. Methods Radiographs of 262 RA patients (mean age 52 years, 66% women) from the BeSt study were scored for osteophytes in DIP/PIP joints using the Osteoarthritis Research Society International atlas (0–3; summed score 0–54) and according to the Kellgren–Lawrence (KL) score (0–4; summed score 0–72) at baseline and 10 year follow-up. TNFi treatment was assessed on visits every 3 months. Associations between TNFi treatment and hand OA were analysed on the patient and joint level using generalized linear models and generalized estimating equations, respectively. Results Fifty-eight percent of the patients were treated with TNFi, with a median duration of 42 months. A total of 143 patients (55%) had hand OA in any IP joint at baseline based on the Osteoarthritis Research Society International osteophyte score. On the patient level, TNFi treatment duration did not affect incidental hand OA. However, every month of TNFi treatment resulted in a reduced relative risk (RR) of hand OA progression in DIP joints [relative risk (RR) 0.987 (95% CI 0.978, 0.996)] but not in PIP joints. On the joint level, the effect on hand OA progression was observed in DIP joints [RR 0.996 (95% CI 0.991, 1.000)] but not in PIP joints. The results from the KL score analyses were comparable to the osteophyte score. Conclusion TNFi treatment was associated with a reduced risk on radiographic hand OA progression in DIP joints but not in PIP joints after 10 years. Although the effect sizes are small, these results provide evidence for influence of TNF-α in hand OA pathogenesis. [ABSTRACT FROM AUTHOR]

The human microbiome project has shown a remarkable diversity of microbial ecology within the human body. The vaginal microbiota is unique in that in many women it is most often dominated by Lactobacillus species. However, in some women it lacks Lactobacillus spp. and is comprised of a wide array of strict and facultative anaerobes, a state that broadly correlates with increased risk for infection, disease, and poor reproductive and obstetric outcomes. Interestingly, the level of protection against infection can also vary by species and strains of Lactobacillus, and some species although dominant are not always optimal. This factors into the risk of contracting sexually transmitted infections and possibly influences the occurrence of resultant adverse reproductive outcomes such as tubal factor infertility. The composition and function of the vaginal microbiota appear to play an important role in pregnancy and fertility treatment outcomes and future research in this field will shed further translational mechanistic understanding onto the interplay of the vaginal microbiota with women's health and reproduction. [ABSTRACT FROM AUTHOR]