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Motivation High-throughput omics methods increasingly result in large datasets including metabolomics data, which are often difficult to analyse. Results To help researchers to handle and analyse those datasets by mapping and investigating metabolomics data of multiple sampling conditions (e.g. different time points or treatments) in the context of pathways, PathwayNexus has been developed, which presents the mapping results in a matrix format, allowing users to easily observe the relations between the compounds and the pathways. It also offers functionalities like ranking, sorting, clustering, pathway views, and further analytical tools. Its primary objective is to condense large sets of pathways into smaller, more relevant subsets that align with the specific interests of the user. Availability and implementation The methodology presented here is implemented in PathwayNexus , an open-source add-on for Vanted available at www.cls.uni-konstanz.de/software/pathway-nexus. Contact falk.schreiber@unikonstanz.de Supplementary information Website: www.cls.uni-konstanz.de/software/pathway-nexus [ABSTRACT FROM AUTHOR]

Objective To investigate pain course over time and to identify baseline and 3-month predictors of unacceptable pain with or without low inflammation in early RA. Methods A cohort of 275 patients with early RA, recruited in 2012–2016, was investigated and followed for 2 years. Pain was assessed using a visual analogue scale (VAS; 0–100 mm). Unacceptable pain was defined as VAS pain >40, and low inflammation as CRP <10 mg/l. Baseline and 3-month predictors of unacceptable pain were evaluated using logistic regression analysis. Results After 2 years, 32% of patients reported unacceptable pain. Among those, 81% had low inflammation. Unacceptable pain, and unacceptable pain with low inflammation, at 1 and 2 years was significantly associated with several factors at 3 months, but not at baseline. Three-month predictors of these pain states at 1 and 2 years were higher scores for pain, patient global assessment, and the health assessment questionnaire, and more extensive joint tenderness compared with the number of swollen joints. No significant associations were found for objective inflammatory measures. Conclusion A substantial proportion of patients had unacceptable pain with low inflammation after 2 years. Three months after diagnosis seems to be a good time-point for assessing the risk of long-term pain. The associations between patient reported outcomes and pain, and the lack of association with objective inflammatory measures, supports the uncoupling between pain and inflammation in RA. Having many tender joints, but more limited synovitis, may be predictive of long-term pain despite low inflammation in early RA. [ABSTRACT FROM AUTHOR]

The given text provides information on an article, a study, and a document related to anorectal malformations (ARM). The article discusses the establishment of a patient registry to collect data on ARM patients, providing insights into demographics, diagnostics, surgeries, complications, and outcomes. The study examines the clinical and surgical characteristics of ARM patients, highlighting the prevalence of associated anomalies and the need for improved postoperative management. The document is a list of references and citations on various aspects of ARM, offering a comprehensive overview of current knowledge and research in the field. [Extracted from the article]

Aims The role of right ventricular function in patients undergoing transcatheter tricuspid valve repair (TTVR) is poorly understood. This study investigated the association of right ventricular ejection fraction (RVEF) assessed by cardiac computed tomography (CCT) with clinical outcomes in patients undergoing TTVR. Methods and results We retrospectively assessed three-dimensional (3D) RVEF by using pre-procedural CCT images in patients undergoing TTVR. RV dysfunction was defined as a CT-RVEF of <45%. The primary outcome was a composite outcome, consisting of all-cause mortality and hospitalization due to heart failure, within 1 year after TTVR. Of 157 patients, 58 (36.9%) presented with CT-RVEF <45%. Procedural success and in-hospital mortality were comparable between patients with CT-RVEF <45% and ≥45%. However, CT-RVEF of <45% was associated with a higher risk of the composite outcome (hazard ratio: 2.99; 95% confidence interval: 1.65–5.41; P = 0.001), which had an additional value beyond two-dimensional echocardiographic assessments of RV function to stratify the risk of the composite outcome. In addition, patients with CT-RVEF ≥45% exhibited the association of procedural success (i.e. residual tricuspid regurgitation of ≤2+ at discharge) with a decreased risk of the composite outcome, while this association was attenuated in those with CT-RVEF <45% (P for interaction = 0.035). Conclusion CT-RVEF is associated with the risk of the composite outcome after TTVR, and a reduced CT-RVEF might attenuate the prognostic benefit of TR reduction. The assessment of 3D-RVEF by using CCT may refine the patient selection for TTVR. [ABSTRACT FROM AUTHOR]

Serpentinites play an important role in the delivery of water into subduction zones. In addition, serpentinites also contain ferric Fe and can transport significant redox potential. We present high-pressure and high-temperature experiments and Mössbauer spectroscopy measurements on natural lizardite and antigorite samples equilibrated at various oxygen fugacities in order to quantify the relationship between the oxygen fugacity f (O2) and the Fe3+/Fetot ratio in these two phases. In antigorite, Fe3+ partitions into the octahedral site and is charge balanced by tetrahedral Al. In lizardite, tetrahedral Fe3+ is observed only at low temperature as well as under high f (O2), whereas Fe3+ prefers the octahedral site at temperatures exceeding 500 °C and at 3 to 5 GPa. Although metastable, lizardite remains in redox equilibrium in our experiments at conditions above the lizardite to antigorite phase transformation at 300 °C and demonstrates a similar stability to antigorite. The Al concentration of lizardite is found to be temperature dependent, and it was possible to reequilibrate the Fe3+/Fetot ratio of lizardite from 0.1 to 0.9 by using redox buffers such as Fe metal, graphite, graphite–calcite, Re–ReO2 and Ru–RuO2. Our experiments on antigorite demonstrate that antigorite does not adjust its Al concentration on experimental time scales. Since Fe3+ is charge balanced by Al, it was also not possible to manipulate the Fe3+/Fetot ratio of antigorite. The coexisting phases, however, show chemical equilibration with this antigorite composition. We have retrieved the standard Gibbs energy for Fe3+- and Al-endmembers of antigorite and lizardite and calculated the metamorphic evolution of subducting serpentinites. The lizardite to antigorite transformation does not cause a decrease in the bulk Fe3+/Fetot ratio under f (O2) buffered conditions, in contrast to observations from some natural settings, but does result in the formation of additional magnetite due to antigorite having a lower Fe3+/Fetot ratio than lizardite at equilibrium. If the f (O2) of antigorite serpentinite is buffered during subduction, such as due to the presence of graphite and carbonate, the bulk Fe3+/Fetot ratio decreases progressively. On the other hand, in a closed system where the bulk serpentinite Fe3+/Fetot ratio remains constant, the f (O2) increases during subduction. In this scenario, the f (O2) of an antigorite serpentinite with a typical Fe3+/Fetot ratio of 0.4 increases from the fayalite–magnetite–quartz to the hematite–magnetite f (O2) buffer during dehydration. These f (O2) results confirm earlier inferences that fluids produced by antigorite dehydration may not contain sufficient oxidised sulphur species to oxidise the mantle wedge. Sufficiently high levels of f (O2) to mobilise oxidised sulphur species may be reached upon antigorite dehydration, however, if closed system behaviour maintains a high bulk redox potential across the lizardite to antigorite phase transformation. Alternatively, oxidation of the mantle wedge might be achieved by oxidising agents from sources in subducted oceanic crust and sediments. [ABSTRACT FROM AUTHOR]

The generation of haploid plants accelerates the crop breeding process. One of the haploidization strategies is based on the genetic manipulation of endogenous centromere-specific histone 3 (CENH3). To extend the haploidization toolbox, we tested whether targeted in vivo degradation of CENH3 protein can be harnessed to generate haploids in Arabidopsis thaliana. We show that a recombinant anti-GFP nanobody fused to either heterologous F-box (NSlmb) or SPOP/BTB ligase proteins can recognize maternally derived enhanced yellow fluorescent protein (EYFP)-tagged CENH3 in planta and make it accessible for the ubiquitin-proteasome pathway. Outcrossing of the genomic CENH3-EYFP-complemented cenh3.1 mother with plants expressing the GFP-nanobody-targeted E3 ubiquitin ligase resulted in a haploid frequency of up to 7.6% in pooled F1 seeds. EYFP-CENH3 degradation occurred independently in embryo and endosperm cells. In reciprocal crosses, no haploid induction occurred. We propose that the uniparental degradation of EYFP-fused genomic CENH3 during early embryogenesis leads to a decrease in its level at centromeres and subsequently weakens the centromeres. The male-derived wild type CENH3 containing centromere outcompetes the CENH3-EYFP depleted centromere. Consequently, maternal chromosomes undergo elimination, resulting in haploids. [ABSTRACT FROM AUTHOR]

Context: Prematurity carries a risk for impaired postnatal growth and long-term growth restriction. Especially children born SGA seem vulnerable for poor growth, as a persistent short stature can be observed in app 10-15% of these children. Objective: In this study we aimed to recognize differences in growth patterns of children according to sex, maturity, and auxological status at birth facilitating earlier identification of small-for-gestational-age (SGA) children with adult short stature. Methods: The growth data of 44 791 infants born between January 1, 1980, and December 30, 2012, among 2 pediatric cohorts with follow-up through December 31, 2020, were analyzed. A total of 5698 children with birth data had measurements at near final height (nfh) and at least 2 further points. Results: Preterm children (gestational age < 37 weeks) had a significantly lower mean nfh SDS than term children (preterm, -0.61; term, -0.18) and a higher likelihood of nfh < third percentile (preterm, 20.5%; term, 12.2%). SGA born children also had a lower mean nfh SD score (SDS) than children born appropriate for gestational age (AGA) (SGA, -1.06; AGA, -0.15) and a higher likelihood of nfh < third percentile (SGA, 28.2%; AGA 10.1%). Of 1204 SGA children, 672 (56%) showed successful catch-up growth (CUG) to nfh greater than or equal to the 10th percentile (SGA-CU), and 532 children (44%) did not (SGA-S). The difference in their mean nfh SDS (SGA-CU, -0.12; SGA-S -2.26) can only partly be explained by the differences in mean mid-parental height SDS (SGA-CU, -0.3; SGA-S, -1.19). During the first year, SGA-CU showed higher CUG (SGA-CU, +1.2 SDS; SGA-S, +0.45 SDS), which helps to discriminate between groups earlier. Conclusion: Final growth outcome was influenced by prematurity and auxological status at birth, but not by sex. Height/length SDS increments during year 1 are instrumental to discern SGA children with later normal or short stature. While observing CUG until year 2 and 3 can add specificity, discrimination thereafter becomes difficult. [ABSTRACT FROM AUTHOR]

This first-ever extensive review of the construction behaviour of orb webs, of webs secondarily derived from orbs, and of non-orbs shows that the evidence favouring monophyly over convergent evolution of orbs is stronger than previously appreciated. The two major orb-weaving groups, Uloboridae and Araneoidea, share 31 construction behaviour traits, 20 of which are likely to be both derived and to have feasible alternatives, making convergence an unlikely explanation. Convergence in two lineages seems unlikely, and convergence in five different lineages, as proposed in some recent molecular studies of phylogeny, is even less credible. A further set of seven shared responses in orb design to experimentally constrained spaces also supports orb monophyly. Finally, a 'control' case of confirmed convergence on similar 'pseudo-orbs' in a taxonomically distant group also supports this argument, as it shows a low frequency of behavioural similarities. I argue that the omission of behavioural data from recent molecular studies of orb web evolution represents a failure of the analytic techniques, not the data, and increases the risk of making mistakes. In general, phylogenetic studies that aim to understand the evolution of particular phenotypes can benefit from including careful study of the phenotypes themselves. [ABSTRACT FROM AUTHOR]

SCORE2-Diabetes: new calibrated models to estimate 10-year risk of cardiovascular disease in individuals with type 2 diabetes in Europe. Likewise, neither diabetes-related retinopathy nor neuropathy, another pair of established CV risk predictors in people with diabetes, was considered. [Extracted from the article]

Context: Adolescent males with hypogonadotropic hypogonadism (HH) have traditionally been treated with exogenous testosterone (T) or human chorionic gonadotropin (hCG) to produce virilization; however, those modalities do not result in growth of the testes and may promote premature maturation and terminal differentiation of Sertoli cells prior to their proliferation, which may impact future fertility. Another option is to use gonadotropins in those individuals to induce testicular growth, proliferation and maturation of Sertoli cells, and production of endogenous T with consequent virilization. Objective: We examined the efficacy and safety of corifollitropin alfa (CFA) combined with hCG for the induction of testicular growth and pubertal development in adolescent boys with HH. Methods: This was a 64-week, multicenter, open-label, single-group study of CFA in adolescent boys, aged 14 to younger than 18 years, with HH. Seventeen participants initiated a 12-week priming period with CFA (100 μg if weight ≤ 60 kg, or 150 μg if weight > 60 kg) given subcutaneously once every 2 weeks, after which they entered a 52-week combined treatment period with CFA, once every 2 weeks, and subcutaneous hCG, twice-weekly (hCG dose adjusted between 500 IU and 5000 IU to keep total T and estradiol levels within protocol-specified ranges). The primary efficacy end point was change from baseline in testicular volume (TV), measured as the sum of volumes of left and right testes by ultrasound. Results: After 64 weeks of therapy with CFA/CFA combined with hCG, geometric mean fold increase from baseline in TV was 9.43 (95% CI, 7.44-11.97) (arithmetic mean of change from baseline at week 64, 13.0 mL). Hormonal, Tanner stage, and growth velocity changes were consistent with initiation and progression of puberty. Treatment was generally well tolerated. No participant developed anti-CFA antibodies. Conclusion: Treatment of adolescent boys with HH with CFA alone for 12 weeks followed by CFA combined with hCG for 52 weeks induced testicular growth accompanied by pubertal progression, increased T, and a pubertal growth spurt (EudraCT: 2015-001878-18). [ABSTRACT FROM AUTHOR]

Context Prediction of adult height (AH) is important in clinical management of short children. The conventional methods of Bayley-Pinneau (BP) or Roche-Wainer-Thissen (RWT) have limitations. Objective We aimed to develop a set of algorithms for AH prediction in patients with idiopathic short stature (ISS) which are specific for combinations of predicting variables. Methods Demographic and auxologic data were collected in childhood (1980s) and at AH (1990s). Data were collected by Dutch and German referral centers for pediatric endocrinology. A total of 292 subjects with ISS (219 male, 73 female) were enrolled. The population was randomly split into modeling (n = 235) and validation (n = 57) cohorts. Linear multi-regression analysis was performed with predicted AH (PAH) as response variable and combinations of chronological age (CA), baseline height, parental heights, relative bone age (BA/CA), birth weight, and sex as exploratory variables. Results Ten models including different exploratory variables were selected with adjusted R² ranging from 0.84 to 0.78 and prediction errors from 3.16 to 3.68 cm. Applied to the validation cohort, mean residuals (PAH minus observed AH) ranged from −0.29 to −0.82 cm, while the conventional methods showed some overprediction (BP: +0.53 cm; RWT: +1.33 cm; projected AH: +3.81 cm). There was no significant trend of residuals with PAH or any exploratory variables, in contrast to BP and projected AH. Conclusion This set of 10 multi-regression algorithms, developed specifically for children with ISS, provides a flexible tool for AH prediction with better accuracy than the conventional methods. [ABSTRACT FROM AUTHOR]

Biases in legal decision-making are difficult to identify as type II errors (wrongful acquittals) are hardly observable and type I errors (wrongful convictions) are only observed for the subsample of subsequently exonerated convicts. Our data on the first German soccer league allow us to classify each referee decision accurately as correct, type I error or type II error. The potential bias we are interested in is favoritism toward clubs with higher long-term status, proxied by the ranking in the all-time table at the beginning of each session and by membership. Higher status clubs benefit largely from fewer type II errors. By contrast, the actual strength of clubs has no impact on referee decisions. We find no difference in type I errors and suggest anticipation of the bias as a potential explanation for the difference. We investigate several mechanisms potentially underlying our results; including career concerns and social pressure (JEL J00, M51, D81, D83). [ABSTRACT FROM AUTHOR]

Purpose The American Association for the Study of Liver Diseases has developed a standard of care for the treatment of patients with spontaneous bacterial peritonitis (SBP). Evidence examining the adherence rate to these guideline recommendations is limited. This study aimed to determine the adherence rate to guideline-directed therapy for patients with cirrhosis hospitalized with SBP. Methods This institutional review board–approved retrospective cohort study conducted at a large academic hospital evaluated the adherence rate to guideline-directed therapy in adult patients with cirrhosis hospitalized with SBP. Included hospitalized patients had a documented diagnosis of cirrhosis and acute SBP. The adherence rate to guideline-directed therapy was determined by receipt of paracentesis within 24 hours of admission, request of Gram stain and culture tests, avoidance of fresh frozen plasma, receipt of albumin on days 1 and 3, receipt of empiric antibiotics within 6 hours, receipt of SBP prophylaxis, receipt of deep vein thrombosis prophylaxis, and offer of pneumococcal vaccination. Results A total of 110 patients were included. Provider adherence to goal-directed therapy was poor, with criteria met for only 10 (9.1%) patients. The therapies with the lowest adherence rates included SBP prophylaxis on discharge (54.5%), receipt of albumin on day 3 (42.7%), and offer of pneumococcal vaccination during admission (43.6%). Patients with a gastrointestinal consult were more likely than those without a consult to obtain albumin on day 1 (69.4% vs 36.8%, P = 0.001) and albumin on day 3 (52.8% vs 23.7%, P = 0.004). Conclusion This study demonstrated a lack of adherence to guideline-directed therapy for the management of SBP. [ABSTRACT FROM AUTHOR]

Objectives Immunosuppressed paediatric patients with rheumatic disease (RD) may be at risk for severe or critical disease related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Data remain scarce on coronavirus disease 2019 (COVID-19) outcomes in paediatric RD patients. The aim of this study was to determine the seroprevalence of SARS-CoV-2 IgG and to describe COVID-19 outcomes in immunosuppressed paediatric RD patients. Methods Patients diagnosed with RD before age 18 years and treated with at least one immunosuppressive medication for at least 3 months were enrolled from a tertiary paediatric rheumatology practice in New York and also underwent routine SARS-CoV-2 IgG testing from May to November 2020. A total of 571 patients were screened and 262 were enrolled. SARS-CoV-2 IgG-positive subjects were assessed for symptoms of COVID-19 infection. SARS-CoV-2 PCR results were recorded where available. Demographic, diagnostic, medication and outcome data were collected. Results Of 262 subjects (186 female), 35 (13%) were SARS-CoV-2 IgG positive; 17 (49%) had symptoms suggestive of COVID-19. Of the 17 patients who had SARS-CoV-2 PCR testing, 11 (65%) were PCR positive, 7 of whom were IgG positive. Most SARS-CoV-2 IgG-positive subjects were not PCR tested. The most common symptoms in IgG- and/or PCR-positive subjects were fever, fatigue and cough. No SARS-CoV-2 IgG- or PCR-positive subject developed severe or critical COVID-19 or required hospitalization. Conclusions This is the first report of clinical outcomes of SARS-CoV-2 infection and seroprevalence of SARS-CoV-2 IgG in a large cohort of paediatric RD patients. Most SARS-CoV-2 IgG-positive subjects had no symptoms of COVID-19 infection. Symptomatic subjects all had mild COVID-19 symptoms, suggesting that the risk of severe or critical COVID-19 in immunosuppressed paediatric RD patients is minimal. [ABSTRACT FROM AUTHOR]

Background Some vaccines elicit nonspecific immune responses that may protect against heterologous infections. We evaluated the association between recombinant adjuvanted zoster vaccine (RZV) and coronavirus disease 2019 (COVID-19) outcomes at Kaiser Permanente Southern California. Methods In a cohort design, adults aged ≥50 years who received ≥1 RZV dose before 1 March 2020 were matched 1:2 to unvaccinated individuals and followed until 31 December 2020. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for COVID-19 outcomes were estimated using Cox proportional hazards regression. In a test-negative design, cases had a positive severe acute respiratory syndrome coronavirus 2 test and controls had only negative tests, during 1 March–31 December 2020. Adjusted odds ratios (aORs) and 95% CIs for RZV receipt were estimated using logistic regression. Results In the cohort design, 149 244 RZV recipients were matched to 298 488 unvaccinated individuals. The aHRs for COVID-19 diagnosis and hospitalization were 0.84 (95% CI,.81–.87) and 0.68 (95% CI,.64–.74), respectively. In the test-negative design, 8.4% of 75 726 test-positive cases and 13.1% of 340 898 test-negative controls had received ≥1 RZV dose (aOR, 0.84 [95% CI,.81–.86]). Conclusions RZV vaccination was associated with a 16% lower risk of COVID-19 diagnosis and 32% lower risk of hospitalization. Further study of vaccine-induced nonspecific immunity for potential attenuation of future pandemics is warranted. [ABSTRACT FROM AUTHOR]

Context Consumption of dietary macronutrients is associated with the progression of a wide range of inflammatory diseases, either by direct modulation of host immune response or via microbiome. This includes periodontitis, a disease affecting tooth-supporting tissues. Objective The aim of this work was to systematically review studies focusing on the effect of macronutrient (ie, carbohydrate, protein, fat) intake on periodontitis in rodents. Data Sources Electronic searches were performed in February 2021 using the PubMed and Web of Science databases. Out of 883 articles reviewed, 23 studies were selected for additional analysis. Data Extraction Investigators extracted relevant data, including author names; the year of publication; article title; macronutrient composition; number and species of animals and their age at the start of the experiment; intervention period; method of periodontitis induction; and primary and secondary periodontitis outcomes. Quality assessment was done using the risk-of-bias tool for animal studies. After completing the data extraction, descriptive statistical information was obtained. Data Analysis High intakes of dietary cholesterol, saturated fatty acids, and processed carbohydrates such as sucrose, and protein-deficient diets were positively associated with periodontitis in rodents. This included greater amounts of alveolar bone loss, more lesions on periodontal tissues, and dental plaque accumulation. In contrast, high doses of milk basic protein in diets and diets with a high ratio of ω-3 to ω-6 fatty acids were negatively associated with periodontitis in rodents. Conclusion This work highlights the fact that, despite the large body of evidence linking macronutrients with inflammation and ageing, overall there is little information on how dietary nutrients affect periodontitis in animal models. In addition, there is inconsistency in data due to differences in methodology, outcome measurement, and dietary formulation. More studies are needed to examine the effects of different dietary macronutrients on periodontitis and investigate the underlying biological mechanisms. [ABSTRACT FROM AUTHOR]

Late gadolinium enhancement with fixed short inversion time (LGEshort) provides excellent tissue contrast with dark scar and bright blood pool and does not need prior myocardial nulling. We hypothesize better visibility of ischemic scars and equal visibility of non-ischemic LGE in LGEshort compared to clinically established LGE (LGEstandard). LGEshort and LGEstandard were retrospectively evaluated in 179 patients (3043 segments) with suspected or known coronary artery disease by four blinded readers (reader A: most experienced - D: least experienced). The amount of ischemic and non-ischemic LGE as well as visibility (4: very good – 1: poor) of ischemic LGE was visually assessed. All readers detected more infarcted segments in LGEshort compared to LGEstandard (378 segments reported as infarcted; A:p = 0.5, B:p = 0.8, C,D:p = 0.03). Scar visibility was scored higher in LGEshort by all readers (A,B:p = 0.03; C,D:p = 0.02), especially for subendocardial infarcts (A,B:p = 0.04, C,D:p = 0.02). Less experienced readers detected significantly more infarcted papillary muscles (C:p = 0.02, D:p = 0.03) in a shorter reading time in LGEshort (C:p = 0.04, D:p = 0.02). Non-ischemic LGE was equally visible in both sequences (A:p = 0.9, B:p = 0.8, C,D:p = 0.6). LGEshort detects more ischemic LGE with improved scar visibility compared to LGEstandard, independent of experience level. The visibility of non-ischemic LGE is equivalent to LGEstandard. Less experienced readers can diagnose ischemic and non-ischemic LGE faster in LGEshort. LGEshort with its maximal operational simplicity can be used for visualization of all types of fibrosis – ischemic and non-ischemic – instead of LGEstandard, independent of experience level. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Computed tomography angiography (CTA) is broadly used for long-term follow-up of graft patency after coronary artery bypass graft surgery (CABG). However, its clinical value in the early postoperative setting has not been established yet. We evaluated the benefit of adding CTA to the routine clinical work-up after CABG on patient management. METHODS A total of 305 consecutive patients (269 males, median age 68 years) underwent CABG and postoperative CTA with a median of 6 days after surgery. Graft patency and additional imaging findings were assessed and their influence on diagnosis and clinical management was evaluated. RESULTS Graft occlusion or high-grade stenosis was found in 15% of the patients. Additional findings were reported in 44% of the patients, including pericardial (2%) and pleural effusion (27%), large pneumothorax (11%), pulmonary infection (4%), cardiac or vascular thrombus (2%), pulmonary embolism (2%), sternal dehiscence (1%) and additional incidental findings requiring follow-up (6%). CT findings initiated new diagnostic and/or therapeutic measures in 15% of the patients, 47% of those with diseased grafts and 19% of patients with non-graft-related findings. No adverse events related to CTA were documented. CONCLUSIONS Early routine postoperative assessment of CABG with CTA reveals both cardiac and non-cardiac findings with a high frequency, affecting clinical management in a substantial proportion of patients. [ABSTRACT FROM AUTHOR]

Learned vocalizations play a key role in parrot social dynamics and vocal dialects have been documented for several mainland species, but to date no studies of geographically structured call variation in parrot species have examined the role of isolation on islands. In a study of the Brown-throated Parakeet (Eupsittula pertinax), which inhabits 5 small Caribbean islands as well as the adjacent mainland, we found that the contact calls of island and mainland parakeets show divergence in vocal characters as well as in call variability. We assessed call variation using 3 approaches: frequency measurements, spectrogram cross-correlation (SPCC) analyses, and call duration measurements. Island parakeets’ calls were longer and had lower mean frequencies, and calls from different islands were distinguishable from each other as well as from mainland calls using measures derived from the SPCCs. In addition, we measured call variability at 2 different levels—within-location and within-individual. We found calls to be more variable for island parakeets for SPCC and duration measures, but less variable for frequency measures. The observed call differentiation among locations may be due to drift, whereas the lower frequency of island calls could either be a response to the windy environment on the islands or a consequence of the island subspecies’ larger body sizes. We also hypothesize that the isolation of parakeet populations on small islands may have resulted in reduced selection for local call convergence, allowing island parakeets to produce more variable calls. We suggest that due to poor signal transmission in the windy island environment, selective pressures may favor variability in more easily perceived call features (like call duration) rather than more subtle features, like frequency shifts. Experimental tests are required to determine whether observed call patterns translate into similarly structured patterns in the responses to vocal variants. [ABSTRACT FROM AUTHOR]

LITMUS was a single-centre, Phase 2a study designed to investigate whether the gene biomarker FGL2/IFNG previously reported for the identification of tolerance in murine models could identify operationally tolerant liver transplant recipients. Multiplex RT-PCR was used to amplify eight immunoregulatory genes in peripheral blood mononuclear cells (PBMC) from 69 adult liver transplant recipients. Patients with PBMC FGL2/IFNG ≥ 1 and a normal liver biopsy underwent immunosuppression (IS) withdrawal. The primary end point was the development of operational tolerance. Secondary end points included correlation of tolerance with allograft gene expression and immune cell markers. Twenty-eight of 69 patients (38%) were positive for the PBMC tolerance biomarker and 23 proceeded to IS withdrawal. Nine of the 23 patients had abnormal baseline liver biopsies and were excluded. Of the 14 patients with normal biopsies, eight (57%) have achieved operational tolerance and are off IS (range 12–57 months). Additional studies revealed that all of the tolerant patients and only one non-tolerant patient had a liver gene ratio of FOXP3/IFNG ≥ 1 prior to IS withdrawal. Increased CD4+ T regulatory T cells were detected both in PBMC and livers of tolerant patients following IS withdrawal. Higher expression of SELE (gene for E-selectin) and lower expression of genes associated with inflammatory responses (GZMB, CIITA, UBD, LSP1, and CXCL9) were observed in the pre-withdrawal liver biopsies of tolerant patients by RNA sequencing. These results suggest that measurement of PBMC FGL2/IFNG may enrich for the identification of operationally tolerant liver transplant patients, especially when combined with intragraft measurement of FOXP3/IFNG. Clinical Trial Registration: ClinicalTrials.gov (LITMUS: NCT02541916). LITMUS was a single-centre, Phase 2 study designed to investigate whether the gene biomarker FGL2/IFNGpreviously reported for the identification of tolerance in murine models could identify operationally tolerant liver transplant recipients. The results suggest that measurement of PBMC FGL2/IFNGmay enrich for the identification of operationally tolerant liver transplant patients, especially when combined with intragraft measurement of FOXP3/IFNG. [ABSTRACT FROM AUTHOR]

Aims  Atherosclerotic cerebrovascular disease underlies the majority of ischaemic strokes and is a major cause of death and disability. While plaque burden is a predictor of adverse outcomes, plaque vulnerability is increasingly recognized as a driver of lesion rupture and risk for clinical events. Defining the molecular regulators of carotid instability could inform the development of new biomarkers and/or translational targets for at-risk individuals. Methods and results  Using two independent human endarterectomy biobanks, we found that the understudied glycoprotein, chitinase 3 like 1 (CHI3L1), is up-regulated in patients with carotid disease compared to healthy controls. Further, CHI3L1 levels were found to stratify individuals based on symptomatology and histopathological evidence of an unstable fibrous cap. Gain- and loss-of-function studies in cultured human carotid artery smooth muscle cells (SMCs) showed that CHI3L1 prevents a number of maladaptive changes in that cell type, including phenotype switching towards a synthetic and hyperproliferative state. Using two murine models of carotid remodelling and lesion vulnerability, we found that knockdown of Chil1 resulted in larger neointimal lesions comprised by de-differentiated SMCs that failed to invest within and stabilize the fibrous cap. Exploratory mechanistic studies identified alterations in potential downstream regulatory genes, including large tumour suppressor kinase 2 (LATS2), which mediates macrophage marker and inflammatory cytokine expression on SMCs, and may explain how CHI3L1 modulates cellular plasticity. Conclusion  CHI3L1 is up-regulated in humans with carotid artery disease and appears to be a strong mediator of plaque vulnerability. Mechanistic studies suggest this change may be a context-dependent adaptive response meant to maintain vascular SMCs in a differentiated state and to prevent rupture of the fibrous cap. Part of this effect may be mediated through downstream suppression of LATS2. Future studies should determine how these changes occur at the molecular level, and whether this gene can be targeted as a novel translational therapy for subjects at risk of stroke. [ABSTRACT FROM AUTHOR]

Background Kidney transplant recipients exhibit a dramatically increased cardiovascular (CV) risk. In 2007, Austrian centres implemented a consensus of comprehensive CV screening programme prior to kidney transplantation (KT). The consensus placed a particular emphasis on screening for coronary artery disease (CAD) with cardiac computed tomography (CT) or coronary angiography (CAG) in patients with diabetes mellitus, known CAD or those having multiple conventional CV risk factors. Here, we investigate if this affected risk stratification and post-transplant CV outcomes. Methods In a retrospective chart review, we evaluated 551 KTs performed from 2003 to 2015 in our centre. Patients were categorized into three groups: KT before (2003–07), directly after (2008–11) and 5 years after (2012–15) implementation of the consensus. We analysed clinical characteristics, the rate of cardiac CTs and CAGs prior to KT as well as major adverse cardiac events (MACEs) during a 2-year follow-up after KT. Results The three study groups showed a homogeneous distribution of comorbidities and age. Significantly more cardiac CTs (13.6% versus 10.2% versus 44.8%; P = 0.002) and CAGs (39.6% versus 43.9% versus 56.2%; P = 0.003) were performed after the consensus. Coronary interventions were performed during 42 out of 260 CAGs (16.2%), the cumulative 2-year MACE incidence was 8.7%. Regarding MACE occurrence, no significant difference between the three groups was found. Conclusion CV risk stratification has become more rigorous and invasive after the implementation of the consensus; however, this was not associated with an improvement in CV outcome. [ABSTRACT FROM AUTHOR]

The global economic impact of reinsurance has increased significantly in recent years, leading to a desire for more certainty in the legal interpretation of reinsurance contracts as the number of disputes increases. Reinsurance contract wordings are not regulated by any overarching statutory law or regulations, in part due to the transnational nature of most reinsurance business. Additionally, reinsurance contracts have historically been interpreted by applying only general principles of contract law and good faith obligations with a heavy emphasis on the parties practice, usage and custom. This has led to significant uncertainty with respect to reinsurance disputes. The Principles of Reinsurance Contract Law (PRICL), published in 2019, aim to bring certainty to reinsurance contracts by improving wordings and developing widely accepted rules of interpretation. [ABSTRACT FROM AUTHOR]

Context Periodontal disease is a chronic inflammatory gum condition that is more prevalent in older populations. The development of periodontal disease has been directly linked to inflammatory dietary habits. Objective This systematic review aimed to 1) describe the relationship and 2) describe the direction of the relationship between dietary intake (nutrients and food groups) and periodontal disease in community-dwelling, older adults. PRISMA guidelines were followed for this review. Data Sources A systematic search of the databases MEDLINE, EMBASE, Global Health, CINAHL, Science Direct, Informit, and Cochrane Library was conducted from the earliest possible date until September 2018. Search terms were related to main themes: "periodontal disease," "gingivitis," "gum diseases," "dietary intake" and "older adults." The search produced 779 records, and after additional publications were obtained and duplicates were removed, 666 publications underwent title and abstract screening. Included papers were written in English and were based on populations of healthy, older adults living in community-based settings. Nine papers met inclusion criteria and were included in this review. Data Extraction Sample size, participant characteristics, inclusion and exclusion criteria, periodontal measures, dietary measures, confounders, and results were sorted by study type, author, year, and country. Data Analysis Quality of the extracted data was analyzed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Conclusions Inverse associations were found between fatty acids, vitamin C, vitamin E, beta-carotene, fiber, calcium, dairy, fruits, and vegetables and risk of periodontal disease. Overall, this review found a relationship between poor dietary intake and increased risk of periodontal disease; however, this needs to be further explored. Systematic Review Registration PROSPERO Registration Number CRD42017065022. [ABSTRACT FROM AUTHOR]

In this paper we introduce and analyze a mixed finite-element approach for a coupled bulk-surface problem of second order with a Wentzell boundary condition. The problem is formulated on a domain with a curved smooth boundary. We introduce a mixed formulation that is equivalent to the usual weak formulation. Furthermore, optimal a priori error estimates between the exact solution and the finite-element approximation are derived. To this end, the curved domain is approximated by a polyhedral domain introducing an additional geometrical error that has to be bounded. A computational result confirms the theoretical findings. [ABSTRACT FROM AUTHOR]

Rapid divergence in external genital structures occurs in nearly all animal groups that practice internal insemination; explaining this pattern is a major challenge in evolutionary biology. The hypothesis that species‐specific differences in male genitalia evolved under sexual selection as courtship devices to influence cryptic female choice (CFC) has been slow to be accepted. Doubts may stem from its radical departure from previous ideas, observational difficulties because crucial events occur hidden within the female's body, and alternative hypotheses involving biologically important phenomena such as speciation, sperm competition, and male‐female conflicts of interest. We assess the current status of the CFC hypothesis by reviewing data from two groups in which crucial predictions have been especially well‐tested, Glossina tsetse flies and Roeseliana (formerly Metrioptera) roeselii bushcrickets. Eighteen CFC predictions have been confirmed in Glossina and 19 in Roeseliana. We found data justifying rejection of alternative hypotheses, but none that contradicted CFC predictions. The number and extent of tests confirming predictions of the CFC hypothesis in these species is greater than that for other generally accepted hypotheses regarding the functions of nongenital structures. By this criterion, it is reasonable to conclude that some genital structures in both groups likely involved sexual selection by CFC. [ABSTRACT FROM AUTHOR]

Sexually-selected traits often show positive static allometry, with large individuals bearing disproportionately large structures. But many other sexually-selected traits show isometry or even negative allometry, with trait size varying relatively little with body size. We recently proposed that the functions of these traits (as aggressive signals, weapons, courtship signals, and contact courtship devices) determine their allometries. Positive allometry is generally favored for aggressive signals because aggressive signals are selected to emphasize body size (and thus fighting prowess). In contrast, the biomechanics of force application in weapons only sometimes select for positive allometry; the content of courtship signals is even less often related to body size; and contact courtship devices are selected to be relatively invariant across body sizes. Here we summarize the arguments in favor of this "functional allometry" hypothesis and expand a comparative test of its predictions. Our results indicate that sexual traits have the allometric slopes predicted by our hypothesis, regardless of which body part bears the structure. [ABSTRACT FROM AUTHOR]

Several interventional treatment options exist in patients with atrial and ventricular arrhythmia. Cardiac CT is routinely performed prior to occlusion of the left atrial appendage, pulmonary vein isolation, and cardiac device implantation. Besides the evaluation of coronary artery disease, cardiac CT provides isotropic, high‐resolution CT images of the cardiac anatomy with the possibility of multiplanar reformations and three‐dimensional reconstructions which are helpful to guide interventional treatment. In addition, cardiac CT is increasingly used to rapidly evaluate periprocedural complications and for the routine post‐procedural imaging surveillance in patients after interventions. This review article will discuss current applications of pre‐ and post‐interventional CT imaging in patients with arrhythmia. [ABSTRACT FROM AUTHOR]

Wasps in the Polysphincta group of Ichneumonidae induce their web-spinning spider hosts to construct modified 'cocoon' webs that support and protect the wasps' cocoons, but the mechanisms used by wasps to manipulate their host spiders have been unclear. We evaluate the hypothesis that wasps manipulate spider ecdysteroid moulting hormones, using the taxonomic distribution of the hosts and cocoon web types of different wasp lineages in the Polysphincta group, with new data comparing cocoon webs with the moulting webs of non-parasitized host spiders. Several predictions were confirmed: wasp and spider species have not co-evolved in a strict sense, with wasp lineages jumping between host lineages; cocoon web designs induced by closely related wasps varied widely in spiders with differing natural histories; cocoon web designs were consistently adjusted to the natural history of the spider in ways promoting wasp survival; and cocoon web designs often resembled those of moulting webs of non-parasitized spiders. Several other types of data did not fit the predictions of simple versions of the ecdysteroid hypothesis, however. We conclude that the use of ecdysteroids by the wasps to manipulate host spider behaviour is probably widespread, but that some wasps might also use other mechanisms. [ABSTRACT FROM AUTHOR]

As the most important male hormone, testosterone has an impact on almost all organs and body functions. The biological effects of testosterone and the testes have been known since antiquity, long before testosterone was identified as the active agent. Practical applications of this knowledge were castration of males to produce obedient servants, for punishment, for preservation of the prepubertal soprano voice and even for treatment of diseases. Testes were used in organotherapy and transplanted as treatment for symptoms of hypogonadism on a large scale, although these practices had only placebo effects. In reaction to such malpractice in the first half of the 20th century science and the young pharmaceutical industry initiated the search for the male hormone. After several detours together with their teams in 1935, Ernst Laqueur (Amsterdam) isolated and Adolf Butenandt (Gdansk) as well as Leopold Ruzicka (Zürich) synthesized testosterone. Since then testosterone has been available for clinical use. However, when given orally, testosterone is inactivated in the liver, so that parenteral forms of administration or modifications of the molecule had to be found. Over 85 years the testosterone preparations have been slowly improved so that now physiological serum levels can be achieved. [ABSTRACT FROM AUTHOR]

We derive optimal order residual-based a posteriori error estimates for fully discrete finite element approximations to the time-dependent Stokes equations. The time discretization uses the two-step backward differentiation formula, and the space discretization is based on inf–sup stable pairs of finite elements, which are allowed to change with time. We show that the time error estimators are of optimal order. This proof of optimality uses time regularity of the semidiscrete (discrete in space) time-dependent Stokes equations. Computational examples are given to confirm the theoretical findings. For completeness, a priori estimates are also presented. [ABSTRACT FROM AUTHOR]

Background High intensity of acute postsurgical pain is one of the strongest predictors of chronic postsurgical pain (CPSP). We investigated if different types of patients with distinct combinations of initial pain intensity and rate of pain resolution exhibit different risks for increased pain intensity six months after surgery. Methods Data from 174 patients were examined using growth mixture analysis by means of structural equation modeling. Results Three types of patients were distinguished on the basis of acute pain trajectories. The majority of patients (57%) showed an unproblematic pattern of little initial pain on the first postoperative day, combined with further pain resolution over the four subsequent days. There also was a substantial group of patients (30%) who started out with severe pain but exhibited a high rate of pain resolution. Finally, we found a problematic group of patients (13%) who reported high pain intensities throughout all five postoperative measurements, with no signs of pain resolution. Even after controlling for preoperative pain intensity, these patients exhibited significantly higher pain intensities six months after surgery than the remaining patient groups. Conclusions In this study, we demonstrated that there is substantial variation in postsurgical pain trajectories, not only with regard to postsurgical initial pain intensity, but also with regard to individual rates of pain resolution. Successful pain resolution appeared to be a better predictor of absence of increased pain intensities six months after surgery than initial pain immediately after surgery. Hence, attention should be given to appropriate pain treatment in order to minimize the risk of CPSP. [ABSTRACT FROM AUTHOR]

Study Question: Is maltreatment during childhood (MC), e.g. sexual abuse, physical abuse, emotional abuse and neglect, associated with diagnosis of endometriosis?Summary Answer: Childhood sexual abuse, emotional abuse/neglect and inconsistency experiences were associated with the diagnosis of endometriosis while no such association was found for physical abuse/neglect and other forms of maltreatment.What Is Known Already: Symptoms of endometriosis such as chronic pelvic pain, fatigue and depression, are correlated with MC, as are immune reactions linked to endometriosis. These factors support a case for a potential role of MC in the development of endometriosis.Study Design, Size, Duration: The study was designed as a multicentre retrospective case-control study. Women with a diagnosis of endometriosis were matched to control women from the same clinic/doctor's office with regard to age (±3 years) and ethnic background. A total of 421 matched pairs were included in the study.Participants/materials, Setting, Methods: Women with endometriosis and control women were recruited in university hospitals, district hospitals, and doctors' offices in Germany, Switzerland and Austria. A German-language version of the Childhood Trauma Questionnaire (CTQ) was used to evaluate MC. Diagnosis of endometriosis was confirmed histologically and classified according to ASRM criteria.Main Results and the Role Of Chance: Women with endometriosis reported significantly more often than control women a history of sexual abuse (20%/14%, P = 0.0197), emotional abuse (44%/28%, P < 0.0001), emotional neglect (50%/42%, P = 0.0123) and inconsistency experiences (53%/41%, P = 0.0007). No statistically significant differences could be demonstrated for physical abuse/neglect (31%/26%, P = 0.1738). Combinations of different abuse/neglect experiences were described significantly more often in women with endometriosis. Frequencies of other MC, i.e. violence against the mother (8%/7%, P = 0.8222), drug abuse in the family (5%/3%, P = 0.0943), mentally handicapped family members (1%/1%, P = 0.7271), suicidal intentions in the family (6%/4%, P = 0.2879) and family members in prison (1%/1%, P = 0.1597) were not statistically different in women with endometriosis and control women.Limitations, Reasons For Caution: Some control women might present asymptomatic endometriosis, which would lead to underestimation of our findings. The exclusion of pregnant women may have biased the results. Statistical power for sub-analyses of physical abuse/neglect and sexual abuse was limited.Wider Implications Of the Findings: A link to MC needs to be considered in women with endometriosis. As there are effective strategies to avoid long-term consequences of MC, healthcare professionals should inquire about such experiences in order to be able to provide treatment for the consequences as early as possible.Study Funding/competing Interest(s): None.Trial Registration Number: Endo_QoL NCT02511626. [ABSTRACT FROM AUTHOR]

Study Question: Is fatigue a frequent symptom of endometriosis?Summary Answer: Fatigue is an underestimated symptom of endometriosis as it affects the majority of women with endometriosis, but it is not widely discussed in literature.What Is Known Already: Fatigue can be a symptom of endometriosis causing major distress impacting the daily activities and quality of life of women with endometriosis. However, few studies with large sample sizes have investigated fatigue as a symptom of endometriosis.Study Design, Size, Duration: The study was designed as a multi-center matched case-control study. Recruitment took place at hospitals and private practices in Switzerland, Germany and Austria between 2010 and 2016. Data was collected from 1120 women, 560 of them with endometriosis. The women with endometriosis were matched to 560 control women in regard to age ±3 years and ethnic background.Participants/materials, Setting, Methods: Diagnosis of women with endometriosis had to be surgically and histologically confirmed. Surgical exclusion or absence of any endometriosis-identifying symptoms was required for control subjects. Materials included surgical and histological reports as well as data retrieved from a self-administered questionnaire. This study focused on the symptom fatigue in endometriosis. Relationships of variables were established by regression analysis and associations were quantified as odds ratios.Main Results and the Role Of Chance: Frequent fatigue was experienced by a majority of women diagnosed with endometriosis (50.7% versus 22.4% in control women, P < 0.001). Fatigue in endometriosis was associated with insomnia (OR: 7.31, CI: 4.62-11.56, P < 0.001), depression (OR: 4.45, CI: 2.76-7.19, P < 0.001), pain (OR: 2.22, CI: 1.52-3.23, P < 0.001), and occupational stress (OR: 1.45, CI: 1.02-2.07, P = 0.037), but was independent of age, time since first diagnosis and stage of the disease.Limitations, Reasons For Caution: Women with asymptomatic endometriosis cannot be excluded in the control group which would lead to underestimation of our results. The study's design allows no evaluation of causal effects.Wider Implications Of the Findings: As fatigue is experienced by numerous women with endometriosis, it needs to be addressed in the discussion of management and treatment of the disease. In addition to treating endometriosis, it would be beneficial to reduce insomnia, depression, pain and occupational stress in order to better manage fatigue.Study Funding/competing Interest(s): There was no additional funding received for this study and no conflict of interest.Trial Registration Number: ClinicalTrials.gov, NCT02511626. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) surface proteins (HBsAg) coat the viral particle and form subviral particles (SVPs). Loss of HBsAg represents a functional cure and is an important treatment goal.Methods: We analyzed the impact of the HBV genotypes A-E and pre-S mutations on SVP expression in hepatitis B virus e antigen (HBeAg)-negative chronic HBV-infected patients. A HBV genome harboring a preS1-deletion was analyzed in hepatoma cells.Results: We observed a genotype-specific ratio of the 3 surface proteins (SHBs/MHBs/LHBs), reflecting differences in the morphology and composition of SVPs. Deletions/mutations in the preS1/preS2 domain, detected in released viral genomes, did not affect the molecular weight of MHBs and LHBs in these patients. In contrast, LHB molecular weight was altered in vitro using an HBV genome harboring a preS1-deletion derived from one of these patients.Conclusion: Differences in composition of SVPs may result in genotype-specific immunogenicity and pathogenesis. In the patients with preS-mutations, secreted HBsAg and released viral genomes cannot be derived from the same genetic source. As viral genomes are derived from covalently closed circular DNA (cccDNA), HBsAg is presumably derived from integrated DNA. This important HBsAg source should be considered for novel antiviral strategies in HBeAg-negative chronic HBV-infected patients. [ABSTRACT FROM AUTHOR]