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White dwarfs with an F, G, or K type companion represent the last common ancestor for a plethora of exotic systems throughout the galaxy, though to this point very few of them have been fully characterized in terms of orbital period and component masses, despite the fact several thousand have been identified. Gaia data release 3 has examined many hundreds of thousands of systems, and as such we can use this, in conjunction with our previous UV excess catalogues, to perform spectral energy distribution fitting in order to obtain a sample of 206 binaries likely to contain a white dwarf, complete with orbital periods, and either a direct measurement of the component masses for astrometric systems, or a lower limit on the component masses for spectroscopic systems. Of this sample of 206, four have previously been observed with Hubble Space Telescope spectroscopically in the ultraviolet, which has confirmed the presence of a white dwarf, and we find excellent agreement between the dynamical and spectroscopic masses of the white dwarfs in these systems. We find that white dwarf plus F, G, or K binaries can have a wide range of orbital periods, from less than a day to many hundreds of days. A large number of our systems are likely post-stable mass transfer systems based on their mass/period relationships, while others are difficult to explain either via stable mass transfer or standard common envelope evolution. [ABSTRACT FROM AUTHOR]

The initial-final mass relation (IFMR) maps the masses of main-sequence stars to their white dwarf descendants. The most common approach to measure the IFMR has been to use white dwarfs in clusters. However, it has been shown that wide double white dwarfs can also be used to measure the IFMR using a Bayesian approach. We have observed a large sample of 90 Gaia double white dwarfs using FORS2 on the VLT. Considering 52 DA + DA, DA + DC, and DC + DC pairs, we applied our extended Bayesian framework to probe the IFMR in exquisite detail. Our monotonic IFMR is well constrained by our observations for initial masses of 1–5 M⊙, with the range of 1–4 M⊙ mostly constrained to a precision of 0.03 M⊙ or better. We add an important extension to the framework, using a Bayesian mixture-model to determine the IFMR robustly in the presence of systems departing from single star evolution. We find a large but uncertain outlier fraction of 59 ± 21 per cent, with outlier systems requiring an additional |$0.70_{-0.22}^{+0.40}$|  Gyr uncertainty in their cooling age differences. However, we find that this fraction is dominated by a few systems with massive components near 0.9 M⊙, where we are most sensitive to outliers, but are also able to establish four systems as merger candidates. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine if controlled substance waste management systems (CSWMS) demonstrate microbial growth, and therefore present a potential infection risk to pediatric hospital patients., Methods: Twenty CSWMS, either Smart Sink or Pharma Lock systems, located in patient care areas were sampled. Twelve were located in critical care areas. Cultures were obtained by swabbing the drain grate with a sterile swab. Swabs were then transported to the microbiology lab for culture. Each sample was labeled with the location of the CSWMS and each system was photographed., Results: Of the CSWMS sampled, 50% demonstrated bacterial or fungal growth with a total of 15 microorganisms isolated, including 3 systems with Micrococcus luteus , 2 with Aspergillus species, and 2 with - Bacillus cereus . Nine of the 15 microorganisms isolated were from systems in the pediatric intensive care unit (PICU) followed by 2 microorganisms in the neonatal intensive care unit (NICU). Of the 12 systems sampled in critical care areas, 8 (66%) had positive cultures. Of the 10 systems which demonstrated growth, 9 were Pharma Lock and 1 was Smart Sink., Conclusion: Controlled substance waste management systems harbor potential pathogens and may serve as reservoirs of infectious agents in pediatric hospitals. Microbial growth was identified in more than half of sampled CSWMS located in critical care areas, where the most vulnerable patients are located. Based on this study, a cleaning procedure for CSWMS should be implemented. Further investigation on the relationship between CSWMS and nosocomial infections is warranted., Competing Interests: Disclosure. The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: membership@pediatricpharmacy.org.)

The activated B cell (ABC) subset of diffuse large B-cell lymphoma (DLBCL) is characterized by chronic B-cell receptor signaling and associated with poor outcomes when treated with standard therapy. In ABC-DLBCL, MALT1 is a core enzyme that is constitutively activated by stimulation of the B-cell receptor or gain-of-function mutations in upstream components of the signaling pathway, making it an attractive therapeutic target. We discovered a novel small-molecule inhibitor, ABBV-MALT1, that potently shuts down B-cell signaling selectively in ABC-DLBCL preclinical models leading to potent cell growth and xenograft inhibition. We also identified a rational combination partner for ABBV-MALT1 in the BCL2 inhibitor, venetoclax, which when combined significantly synergizes to elicit deep and durable responses in preclinical models. This work highlights the potential of ABBV-MALT1 monotherapy and combination with venetoclax as effective treatment options for patients with ABC-DLBCL., (©2024 The Authors; Published by the American Association for Cancer Research.)

Quadricuspid pulmonic valve is a rare congenital abnormality and because of its difficult non-invasive assessment, it is usually discovered incidentally at autopsies (reported prevalence in post-mortem specimens ranges from 1 in 400 to 1 in 2000). Unlike a bicuspid pulmonary valve, it rarely presents with clinical complications, such as valvular insufficiency or stenosis. Abnormal function is rarely reported in cases that are not associated with other congenital heart disease. With increased sophistication of imaging coincidental quadricuspid valves autopsy studies are important to understand the anatomical consequences of this finding. Our case series identified 21 QPV cases from the Victorian Institute of Forensic Medicine, Melbourne and St George's University of London, Department of Cardiovascular Pathology. Cases were identified through local database searches and review of autopsy/cardiac examination reports over a 20-year period. Available photographs were also systematically examined. Fifteen cases had causes of death with no direct causality to cardiac valvular pathology alone. Six cases were considered unascertained or similar (sudden arrhythmic death syndrome and sudden unexpected death in epilepsy). The presence of QPV in these instances were uncertain but thought to be unlikely contributory to death, due to the absence of pulmonary valvular complications., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Gastric volvulus is a rare cause of gastric obstruction, due to the rotation of the stomach by more than 180°. It is a rare but life-threatening medical emergency that is considered difficult to diagnose at the initial clinical presentation. Forensic pathologists may be presented with gastric volvulus in several ways, for instance, as a cause of sudden and unexpected death or in the context of suspected clinical errors. The post-mortem examination of gastric volvulus may be challenging, due to the specific technical issues it presents and the various mechanisms by which volvulus may cause death. We therefore present five cases of gastric volvulus that in combination represent almost the entire spectrum of presentations and post-mortem findings, to discuss how gastric volvulus may come to the attention of a forensic pathologist, the approach and findings at post-mortem examination (including post-mortem CT), and the variety of mechanisms by which gastric volvulus may result in death., (© 2023. Crown.)

Objective: Effective health communication is critical for understanding and acting on health information. This cross-sectional study explored participants' understanding of their health condition, their preferences for receiving health communications, and their interest in receiving clinical trial results across several therapeutic areas., Methods: The study recruited participants via social media, email newsletters, and advocacy organizations. An online screener captured demographic information (health conditions, age, race/ethnicity, gender, and education). Eligible participants were emailed an online survey assessing preferred sources and formats for receiving health information, interest in learning about topics related to the results of clinical trials, and health literacy levels., Results: In total, 449 participants (median age, 35 years [range, 18-76]; White, 53%; higher education, 65%; mean (range) health literacy score, 1.9 [0.4-3.0]) from 45 US states completed the survey representing 12 disease indications (bipolar, blood and solid tumor cancers, irritable bowel syndrome, inflammatory bowel disease, major depressive disorder, migraine, Parkinson's, psoriasis/atopic dermatitis, retinal vein occlusion/macular degeneration, rheumatoid arthritis, and spasticity). Healthcare providers were the preferred source of health information (59%), followed by Internet searches (11%). Least preferred sources were social media (5%), friends/family (3%), and email newsletters (2%). Participants preferred multiple formats and ranked reading materials online as most preferred (33%), along with videos (28%) and infographics (27%). Printed materials (14%) and audio podcasts (9%) were the least preferred formats. A majority of the participants reported that the health information they found was hard to understand (57%) and confusing (62%). Most participants (85%) were somewhat/very interested in learning about clinical trial results, with the highest interest in short summaries of safety (78%) and efficacy (74%) results., Conclusion: Effective health communication may be achieved via multiple formats shared directly by healthcare providers.

SMARCA4 encodes one of two mutually exclusive ATPase subunits in the BRG/BRM associated factor (BAF) complex that is recruited by transcription factors (TFs) to drive chromatin accessibility and transcriptional activation. SMARCA4 is among the most recurrently mutated genes in human cancer, including ∼30% of germinal center (GC)-derived Burkitt lymphomas. In mice, GC-specific Smarca4 haploinsufficiency cooperated with MYC over-expression to drive lymphomagenesis. Furthermore, monoallelic Smarca4 deletion drove GC hyperplasia with centroblast polarization via significantly increased rates of centrocyte recycling to the dark zone. Mechanistically, Smarca4 loss reduced the activity of TFs that are activated in centrocytes to drive GC-exit, including SPI1 (PU.1), IRF family, and NF-κB. Loss of activity for these factors phenocopied aberrant BCL6 activity within murine centrocytes and human Burkitt lymphoma cells. SMARCA4 therefore facilitates chromatin accessibility for TFs that shape centrocyte trajectories, and loss of fine-control of these programs biases toward centroblast cell-fate, GC hyperplasia and lymphoma., Competing Interests: Declaration of interests C.A., advisory board for Sobi and OPNA, research funding from Genentech. A.M., research funding from Janssen, Epizyme and Daiichi Sankyo, consulting for Exo Therapeutics, Treeline Biosciences, Astra Zeneca, Epizyme. C.S., consulting for Seattle Genetics, AbbVie, and Bayer, research funding from Bristol Myers Squibb, Epizyme and Trillium Therapeutics Inc. C.E.M. is a cofounder and board member for Biotia and Onegevity Health, advisor or grantee for Abbvie, ArcBio, Daiichi Sankyo, DNA Genotek, Tempus Labs, and Whole Biome. M.R.G., research funding from Sanofi, Kite/Gilead, Allogene and Abbvie, honoraria from Daiichi Sankyo, Abbvie and DAVA Oncology., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Emerging neuroimaging studies investigating changes in the brain aim to collect sufficient data points to examine trajectories of change across key developmental periods. Yet, current studies are often constrained by the number of time points available now. We demonstrate that these constraints should be taken seriously and that studies with two time points should focus on particular questions (e.g., group-level or intervention effects), while complex questions of individual differences and investigations into causes and consequences of those differences should be deferred until additional time points can be incorporated into models of change. We generated underlying longitudinal data and fit models with 2, 3, 4, and 5 time points across 1000 samples. While fixed effects could be recovered on average even with few time points, recovery of individual differences was particularly poor for the two time point model, correlating at r = 0.41 with the true individual parameters - meaning these scores share only 16.8% of variance As expected, models with more time points recovered the growth parameter more accurately; yet parameter recovery for the three time point model was still low, correlating around r = 0.57. We argue that preliminary analyses on early subsets of time points in longitudinal analyses should focus on these average or group-level effects and that individual difference questions should be addressed in samples that maximize the number of time points available. We conclude with recommendations for researchers using early time point models, including ideas for preregistration, careful interpretation of 2 time point results, and treating longitudinal analyses as dynamic, where early findings are updated as additional information becomes available., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Sexual minority youth are at higher risk of self-harming than heterosexual adolescents. Understanding why sexual minority youth are more vulnerable to poor mental health and identifying factors that might buffer against this risk is important for developing targeted interventions. We used the Millennium Cohort Study to investigate whether same-sex attraction at age 14 is associated with suicide attempts and self-harm at age 17. Additionally, we tested whether bullying victimisation might mediate any observed associations, and whether social support might protect against any increased risk. Sexual minority youth were 2.44 times more likely to attempt suicide and 2.59 times more likely to self-harm aged 17. There was no evidence for an association between greater social support and lower levels of self-harm. However, greater social support in sexual minority youth is associated with reduced risk for suicide attempt. Bullying partially mediated the relationship between same-sex attraction and mental health. Greater levels in bullying in sexual minority youth were associated with 1.32 times higher risk for suicide and 1.30 times higher risk for self-harm. Social support was not associated with reduced risk of suicide attempt or self-harm among bullied sexual minority youth. Sexual minority youth in the UK are at higher risk for suicide attempt and self-harm. To address this disparity, health and educational practitioners should understand this heightened risk for poor mental health, and address bullying as one risk factor. Further interventions are needed to assist sexual minority youth beyond social support provision through friends and family., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Patients diagnosed with advanced-stage Hodgkin lymphoma (aHL) have historically been risk-stratified using the International Prognostic Score (IPS). This study investigated if a machine learning (ML) approach could outperform existing models when it comes to predicting overall survival (OS) and progression-free survival (PFS)., Patients and Methods: This study used patient data from the Danish National Lymphoma Register for model development (development cohort). The ML model was developed using stacking, which combines several predictive survival models (Cox proportional hazard, flexible parametric model, IPS, principal component, penalized regression) into a single model, and was compared with two versions of IPS (IPS-3 and IPS-7) and the newly developed aHL international prognostic index (A-HIPI). Internal model validation was performed using nested cross-validation, and external validation was performed using patient data from the Swedish Lymphoma Register and Cancer Registry of Norway (validation cohort)., Results: In total, 707 and 760 patients with aHL were included in the development and validation cohorts, respectively. Examining model performance for OS in the development cohort, the concordance index (C-index) for the ML model, IPS-7, IPS-3, and A-HIPI was found to be 0.789, 0.608, 0.650, and 0.768, respectively. The corresponding estimates in the validation cohort were 0.749, 0.700, 0.663, and 0.741. For PFS, the ML model achieved the highest C-index in both cohorts (0.665 in the development cohort and 0.691 in the validation cohort). The time-varying AUCs for both the ML model and the A-HIPI were consistently higher in both cohorts compared with the IPS models within the first 5 years after diagnosis., Conclusion: The new prognostic model for aHL on the basis of ML techniques demonstrated a substantial improvement compared with the IPS models, but yielded a limited improvement in predictive performance compared with the A-HIPI.

Molecular crystal structures are often interpreted in terms of strong, structure directing, intermolecular interactions, especially those with distinct geometric signatures such as H-bonds or π-stacking interactions. Other interactions can be overlooked, perhaps because they are weak or lack a characteristic geometry. We show that although the cumulative effect of weak interactions is significant, their deformability also leads to occupation of low energy vibrational energy levels, which provides an additional stabilizing entropic contribution. The entropies of five fluorobenzene derivatives have been calculated by periodic DFT calculations to assess the entropic influence of C-H···F interactions in stabilizing their crystal structures. Calculations reproduce inelastic neutron scattering data and experimental entropies from heat capacity measurements. C-H···F contacts are shown to have force constants which are around half of those of more familiar interactions such as hydrogen bonds, halogen bonds, and C-H···π interactions. This feature, in combination with the relatively high mass of F, means that the lowest energy vibrations in crystalline fluorobenzenes are dominated by C-H···F contributions. C-H···F contacts occur much more frequently than would be expected from their enthalpic contributions alone, but at 150 K, the stabilizing contribution of entropy provides, at -10 to -15 kJ mol -1 , a similar level of stabilization to the N-H···N hydrogen bond in ammonia and O-H···O hydrogen bond in water., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Creating a welcoming and supportive environment for learners with disabilities needs to be a focus within pharmacy education. Including students with disabilities enhances program diversity and contributes to awareness and understanding of disability. Barriers to embracing disability include stigma toward disability, insufficient resource allocation, and misunderstanding of accommodations. Steps that need to be taken to embrace disability include evaluation of current programmatic culture, provision of education, and collaboration with external stakeholders. Schools/colleges of pharmacy must move toward a framework that embraces disability within our programs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background: Ketamine has traditionally been avoided for tracheal intubations (TIs) in patients with acute neurological conditions. We evaluate its current usage pattern in these patients and any associated adverse events., Methods: We conducted a retrospective observational cohort study of critically ill children undergoing TI for neurological indications in 53 international pediatric intensive care units and emergency departments. We screened all intubations from 2014 to 2020 entered into the multicenter National Emergency Airway Registry for Children (NEAR4KIDS) registry database. Patients were included if they were under the age of 18 years and underwent TI for a primary neurological indication. Usage patterns and reported periprocedural composite adverse outcomes (hypoxemia < 80%, hypotension/hypertension, cardiac arrest, and dysrhythmia) were noted., Results: Of 21,562 TIs, 2,073 (9.6%) were performed for a primary neurological indication, including 190 for traumatic brain injury/trauma. Patients received ketamine in 495 TIs (23.9%), which increased from 10% in 2014 to 41% in 2020 (p < 0.001). Ketamine use was associated with a coindication of respiratory failure, difficult airway history, and use of vagolytic agents, apneic oxygenation, and video laryngoscopy. Composite adverse outcomes were reported in 289 (13.9%) Tis and were more common in the ketamine group (17.0% vs. 13.0%, p = 0.026). After adjusting for location, patient age and codiagnoses, the presence of respiratory failure and shock, difficult airway history, provider demographics, intubating device, and the use of apneic oxygenation, vagolytic agents, and neuromuscular blockade, ketamine use was not significantly associated with increased composite adverse outcomes (adjusted odds ratio 1.34, 95% confidence interval CI 0.99-1.81, p = 0.057). This paucity of association remained even when only neurotrauma intubations were considered (10.6% vs. 7.7%, p = 0.528)., Conclusions: This retrospective cohort study did not demonstrate an association between procedural ketamine use and increased risk of peri-intubation hypoxemia and hemodynamic instability in patients intubated for neurological indications., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Pericardial effusion can be a sign of significant underlying diease and, in some cases, may lead to death. Post-mortem computed tomography (PMCT) is a well-established tool to assist death investigation processes in the forensic setting. In practice, the scarcity of well-trained radiologists is a challenge in processing raw whole-body PMCT images for pericardial effusion detection. In this work, we propose a Pericardial Effusion Automatic Detection (PEAD) framework to automatically process raw whole-body PMCT images to filter out the irrelevant images with heart organ absent and focus on pericardial effusion detection. In PEAD, the standard convolutional neural network architectures of VGG and ResNet are carefully modified to fit the specific characteristics of PMCT images. The experimental results prove the effectiveness of the proposed framework and modified models. The modified VGG and ResNet models achieved superior detection accuracy than the standard architecture with reduced processing speed.

The Cognitive Bias (CogBIAS) hypothesis proposes that cognitive biases develop as a function of environmental influences (which determine the valence of biases) and the genetic susceptibility to those influences (which determines the potency of biases). The current study employed a longitudinal, polygenic-by-environment approach to examine the CogBIAS hypothesis. To this end, measures of life experiences and polygenic scores for depression were used to assess the development of memory and interpretation biases in a three-wave sample of adolescents (12-16 years) ( N = 337). Using mixed effects modeling, three patterns were revealed. First, positive life experiences (PLEs) were found to diminish negative and enhance positive forms of memory and social interpretation biases. Second, and against expectation, negative life experiences and depression polygenic scores were not associated with any cognitive outcomes, upon adjusting for psychopathology. Finally, and most importantly, the interaction between high polygenic risk and greater PLEs was associated with a stronger positive interpretation bias for social situations. These results provide the first line of polygenic evidence in support of the CogBIAS hypothesis, but also extend this hypothesis by highlighting positive genetic and nuanced environmental influences on the development of cognitive biases across adolescence.

This study investigated methylamphetamine (MA) exposures in the deaths of children (≤ 12 years old) reported to the Coroner in the state of Victoria, Australia, between 2011 and 2020. Demographics, autopsy findings including the cause of death, self-reported prenatal or caregiver drug use, child protection services information, and toxicological findings were summarized by descriptive statistics. Validated methods of liquid chromatography-tandem mass spectrometry were used in the analysis of drugs. There were 50 child deaths with MA detected in blood, urine, and/or hair with 64% (n = 32) identified in 2018-2020. Most children were 1-365 days old (66%, n = 33) and the cause of death was unascertained in 62% (n = 31) of cases. MA was toxicologically confirmed in hair (94%, n = 47) significantly more than blood (18%, n = 9). Prenatal or caregiver drug use was self-reported in 44% (n = 22) and 42% (n = 21) of cases, respectively. Moreover, only 54% (n = 27) of deceased children were a child protection client at their time of death. These findings suggest the number of deceased children exposed to MA has increased over the past 10 years, which is consistent with the greater supply of crystal MA in the Australian community. Hair analysis provided additional means to identify cases that were unknown to child protection services and may have implications for other children in the same drug exposure environment., (© 2024. The Author(s).)

Background: Chronic pain is a major challenge for some people after total knee replacement (TKR). The changing impact of this complication during the first post-operative year remains unclear. This analysis aimed to examine how physical activity and health-related quality of life (HRQoL) evolved over the first year after TKR for patients with and without post-operative chronic knee pain., Methods: We conducted a secondary analysis of data from a randomised controlled trial (PEP-TALK), which tested the effectiveness of a behaviour change physiotherapy intervention compared with usual rehabilitation after TKR. Mean UCLA Activity Score and EQ-5D-5L for participants with and without chronic knee pain (14 points or lower in the Oxford Knee Score Pain Subscale (OKS-PS) at six months post-TKR) were compared at six and 12 months post-TKR., Results: Data from 83 participants were analysed. For those with chronic knee pain, UCLA Activity Score remained unchanged between baseline to six months (mean: 3.8 to 3.8), decreasing at 12 months (3.0). Those without post-operative chronic knee pain reported improved physical activity from baseline to six months (4.0 vs 4.9), plateauing at 12 months (4.9). Participants with chronic knee pain reported lower baseline HRQoL (0.28 vs 0.48). Both groups improved health utility over one year. Of those without chronic pain at six months, 8.5% returned to chronic pain by 12 months., Conclusions: Monitoring clinical outcomes after six months may be indicated for those at risk of chronic pain post-TKR. Further, sufficiently powered analyses are warranted to increase the generalisability of this exploratory analyses' results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)