Identification of Predictive Biomarkers of Lameness in Transition Dairy Cows.

The aim of this study was to identify with a high level of confidence metabolites previously identified as predictors of lameness and understand their biological relevance by carrying out pathway analyses. For the dairy cattle sector, lameness is a major challenge with a large impact on animal welfare and farm economics. Understanding metabolic alterations during the transition period associated with lameness before the appearance of clinical signs may allow its early detection and risk prevention. The annotation with high confidence of metabolite predictors of lameness and the understanding of interactions between metabolism and immunity are crucial for a better understanding of this condition. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with authentic standards to increase confidence in the putative annotations of metabolites previously determined as predictive for lameness in transition dairy cows, it was possible to identify cresol, valproic acid, and gluconolactone as L1, L2, and L1, respectively which are the highest levels of confidence in identification. The metabolite set enrichment analysis of biological pathways in which predictors of lameness are involved identified six significant pathways (p < 0.05). In comparison, over-representation analysis and topology analysis identified two significant pathways (p < 0.05). Overall, our LC-MS/MS analysis proved to be adequate to confidently identify metabolites in urine samples previously found to be predictive of lameness, and understand their potential biological relevance, despite the challenges of metabolite identification and pathway analysis when performing untargeted metabolomics. This approach shows potential as a reliable method to identify biomarkers that can be used in the future to predict the risk of lameness before calving. Validation with a larger cohort is required to assess the generalization of these findings.

Enhancing Neoadjuvant Virotherapy's Effectiveness by Targeting Stroma to Improve Resectability in Pancreatic Cancer.

About one-fourth of patients with pancreatic ductal adenocarcinoma (PDAC) are categorized as borderline resectable (BR) or locally advanced (LA). Chemotherapy and radiation therapy have not yielded the anticipated outcomes in curing patients with BR/LA PDAC. The surgical resection of these tumors presents challenges owing to the unpredictability of the resection margin, involvement of vasculature with the tumor, the likelihood of occult metastasis, a higher ratio of positive lymph nodes, and the relatively larger size of tumor nodules. Oncolytic virotherapy has shown promising activity in preclinical PDAC models. Unfortunately, the desmoplastic stroma within the PDAC tumor microenvironment establishes a barrier, hindering the infiltration of oncolytic viruses and various therapeutic drugs-such as antibodies, adoptive cell therapy agents, and chemotherapeutic agents-in reaching the tumor site. Recently, a growing emphasis has been placed on targeting major acellular components of tumor stroma, such as hyaluronic acid and collagen, to enhance drug penetration. Oncolytic viruses can be engineered to express proteolytic enzymes that cleave hyaluronic acid and collagen into smaller polypeptides, thereby softening the desmoplastic stroma, ultimately leading to increased viral distribution along with increased oncolysis and subsequent tumor size regression. This approach may offer new possibilities to improve the resectability of patients diagnosed with BR and LA PDAC.

COVID-19 related myocardial injury is associated with immune dysregulation in symptomatic patients with cardiac MRI abnormalities.

AIMS: While acute cardiovascular complications of COVID-19 are well-described, less is known about longer-term cardiac sequelae. For many individuals with cardiac signs or symptoms arising after COVID-19 infection, the aetiology remains unclear. We examined immune profiles associated with magnetic resonance imaging (MRI) abnormalities in patients with unexplained cardiac injury after COVID-19. METHODS AND RESULTS: Twenty-one participants (mean age 47 [SD 13] years, 71% female) with long COVID (n=17), raised troponin (n=2), or unexplained new-onset heart failure (n=2), who did not have pre-existing heart conditions or recent steroid/immunosuppression treatment were enrolled a mean 346 (SD 191) days after COVID-19 infection in a prospective observational study. Cardiac MRI and blood sampling for deep immunophenotyping using mass cytometry by time of flight and measurement of proteomic inflammatory markers was performed. Nine of 21 (43%) participants had MRI abnormalities (MRI(+)), including non-ischaemic patterns of late gadolinium enhancement and/or visually overt myocardial oedema in 8 people. One patient had mildly impaired biventricular function without fibrosis or oedema, and 2 had severe left ventricular impairment. MRI(+) individuals had higher blood CCL3, CCL7, FGF-23 and CD4 Th2 cells, and lower CD8 T effector memory (TEM) cells, than MRI(-). Cluster analysis revealed lower expression of inhibitory receptors PD1 and TIM3 in CD8 TEM cells from MRI(+) patients than MRI(-) patients, and functional studies of CD8 T αß cells showed higher proportions of cytotoxic granzyme B+ secreting cells upon stimulation. CD8 TEM cells and CCL7 were the strongest predictors of MRI abnormalities in a LASSO regression model (composite AUC 0.96, 95%CI 0.88-1.0). CCL7 was correlated with diffuse myocardial fibrosis/oedema detected by quantitative T1 mapping (r=0.47, p=0.04). CONCLUSION: COVID-19 related cardiac injury in symptomatic patients with non-ischaemic myocarditis-like MRI abnormalities is associated with immune dysregulation, including decreased peripheral CD8 TEM cells and increased CCL7, persisting long after the initial infection.

SNO-EANO-EURACAN consensus on management of pineal parenchymal tumors.

Pineal parenchymal tumors are rare neoplasms for which evidence-based treatment recommendations are lacking. These tumors vary in biology, clinical characteristics, and prognosis, requiring treatment that ranges from surgical resection alone to intensive multimodal antineoplastic therapy. Recently, international collaborative studies have shed light on the genomic landscape of these tumors, leading to refinement in molecular-based disease classification in the 5th edition of the World Health Organization (WHO) classification of tumors of the central nervous system. In this review, we summarize the literature on diagnostic and therapeutic approaches, and suggest pragmatic recommendations for the clinical management of patients presenting with intrinsic pineal region masses including parenchymal tumors (pineocytoma, pineal parenchymal tumor of intermediate differentiation, and pineoblastoma), pineal cyst, and papillary tumors of the pineal region.

HIV broadly neutralizing antibody escapability drives the therapeutic efficacy of vectored immunotherapy.

Broadly neutralizing antibodies (bNAbs) have shown great promise for prevention and treatment of HIV infection. Breadth of bNAb neutralization, measured in vitro across panels of diverse viral isolates, is often used as a predictor of clinical potential. However, recent prevention studies demonstrate that the clinical efficacy of a broad and potent bNAb (VRC01) is undermined by neutralization resistance of circulating strains. Using HIV-infected humanized mice, we find that therapeutic efficacy of bNAbs delivered as Vectored ImmunoTherapy (VIT) is a function of both the fitness cost and resistance benefit of mutations that emerge during viral escape, which we term 'escapability'. Applying this mechanistic framework, we find that the sequence of the envelope V5-loop alters the resistance benefits of mutants that arise during escape, thereby impacting the therapeutic efficacy of VIT-mediated viral suppression. We also find that an emtricitabine-based antiretroviral drug regimen dramatically enhances the efficacy of VIT, by reducing the fitness of mutants along the escape path. Our findings demonstrate that bNAb escapability is a key determinant to consider in the rational design of antibody regimens with maximal efficacy and illustrates a tractable means of minimizing viral escape from existing bNAbs.

Understanding Barriers to Guideline-Concordant Treatment in Foregut Cancer: From Data to Solutions.

BACKGROUND: A large proportion of patients with foregut cancers do not receive guideline-concordant treatment (GCT). This study sought to understand underlying barriers to GCT through a root cause analysis approach. METHODS: A single-institution retrospective review of 498 patients with foregut (gastric, pancreatic, and hepatobiliary) adenocarcinoma from 2018 to 2022 was performed. Guideline-concordant treatment was defined based on National Comprehensive Cancer Network guidelines. The Ishikawa cause and effect model was used to establish main contributing factors to non-GCT. RESULTS: Overall, 34% did not receive GCT. Root causes of non-GCT included Patient, Physician, Institutional Environment and Broader System-related factors. In decreasing order of frequency, the following contributed to non-GCT: receipt of incomplete therapy (N = 28, 16.5%), deconditioning on chemotherapy (N = 26, 15.3%), delays in care because of patient resource constraints followed by loss to follow-up (N = 19, 11.2%), physician factors (N = 19, 11.2%), no documentation of treatment plan after referral to oncologic expertise (N = 19, 11.2%), loss to follow-up before oncology referral (N = 17, 10%), nonreferral to medical oncologic expertise (N = 16, 9.4%), nonreferral to surgical oncology in patients with resectable disease (N = 15, 8.8%), and complications preventing completion of treatment (N = 11, 6.5%). Non-GCT often was a function of multiple intersecting patient, physician, and institutional factors. CONCLUSIONS: A substantial percentage of patients with foregut cancer do not receive GCT. Solutions that may improve receipt of GCT include development of automated systems to improve patient follow-up; institutional prioritization of resources to enhance staffing; financial counseling and assistance programs; and development and integration of structured prehabilitation programs into cancer treatment pathways.

Frailty, multimorbidity and polypharmacy: exploratory analyses of the effects of empagliflozin from the EMPA-KIDNEY trial.

BACKGROUND: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are recommended treatment for adults with chronic kidney disease (CKD), but uncertainty exists regarding their use in patients with frailty and/or multimorbidity, among whom polypharmacy is common. We derived a multivariable logistic regression model to predict hospitalization (reflecting frailty) and assessed empagliflozin's risk-benefit profile in a post-hoc analysis of the double-blind, placebo-controlled EMPA-KIDNEY trial. METHODS: The EMPA-KIDNEY trial randomized 6609 patients with CKD (estimated glomerular filtration rate [eGFR] ≥20<45 mL/min/1.73m2, or ≥45<90 mL/min/1.73m2 with urinary albumin-to-creatinine ratio ≥200 mg/g) to receive either empagliflozin 10 mg daily or matching placebo and followed for two years (median). Additional characteristics analysed in subgroups were multimorbidity, polypharmacy and health-related quality of life (HRQoL) at baseline. Cox regression analyses were performed with subgroups defined by approximate thirds of each variable. RESULTS: The strongest predictors of hospitalization were N-terminal prohormone of brain natriuretic peptide, poor mobility and diabetes; then eGFR and other comorbidities. Empagliflozin was generally well-tolerated independent of predicted risk of hospitalization. In relative terms, allocation to empagliflozin reduced the risk of the primary outcome of kidney disease progression or cardiovascular death by 28% (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.64-0.82); and all-cause hospitalization by 14% (HR 0.86, 95% CI 0.78-0.95); with broadly consistent effects across subgroups of predicted risk of hospitalization, multimorbidity, polypharmacy or HRQoL. In absolute terms, the estimated benefits of empagliflozin were greater in those at highest predicted risk of hospitalization (reflecting frailty) and outweighed potential serious harms. CONCLUSIONS: These findings support the use of SGLT2 inhibitors in CKD, irrespective of frailty, multimorbidity or polypharmacy.

Changes to certain extIPA diacritics.

This short note outlines changes to three of the diacritics on the extIPA chart and provides an updated version of the entire chart.

Novel use of a servosphere to study apodous insects: Investigation of blow fly post-feeding larval dispersal.

Blow flies (Diptera: Calliphoridae) are arguably the most important providers of an estimate of minimum post-mortem interval in forensic investigations. They usually undergo a post-feeding dispersal from the body. While previous studies have looked at dispersal of groups of larvae, recording the dispersal activity of individual larvae has not previously been demonstrated. A servosphere was used here to record the speed, directionality and phototaxis of individual post-feeding larvae of two species of blow fly on a smooth plastic surface over time. The servosphere rotates to compensate for the movement of an insect placed at its apex, thereby enabling its unimpeded locomotion in any direction to be studied and behavioural changes to external stimuli recorded. To our knowledge, the servosphere has not previously been used to study apodous insects. The objective of our study was to compare dispersal behaviour of Calliphora vicina Robineau-Desvoidy and Protophormia terraenovae (Robineau-Desvoidy), both common primary colonisers of human and animal cadavers, but showing different post-feeding dispersal strategies. Larvae of C. vicina generally disperse from the body while those of P. terraenovae remain on or close to the body. Our aims were to study (1) changes in dispersal speed over a 1-h period; (2) changes in dispersal speed once a day for 4 days, between the end of feeding and onset of pupariation; and (3) response of dispersing larvae to light. We demonstrated that (1) the movement of three C. vicina larvae tracked for 1 continuous hour on 1 day slowed from an average of 3 to <1.7 mms-1; (2) the average speed of 20 larvae of C. vicina (4.08 mms-1) recorded for 5 min once per day over a 4-day period between onset of dispersal and pupariation was significantly greater than that of P. terraenovae (2.36 mms-1; p < 0.0001), but that speed of both species increased slightly over the 4 days; (3) the responses of larvae of C. vicina to changes in light direction from the four cardinal directions of the compass, showed that they exhibited a strong negative phototactic response within 5 s, turning to move at approximately 180° away from the new light position. While conducted to observe larval calliphorid post-feeding behaviour, the results of this proof of concept study show that apodous insects can be studied on a servosphere to produce both qualitative and quantitative data.

Poststroke cognitive outcome is better accounted for by white matter abnormalities automated segmentation than visual analysis.

BACKGROUND AND AIMS: The association between white matter abnormalities (WMA) and cognitive decline previously reported in poststroke patients has been mainly documented using visual scales. However, automated segmentation of WMA provides a precise determination of the volume of WMA. Nonetheless, it is rarely used in the stroke population and its potential advantage over visual scales is still unsettled. The objective of this study was to examine whether automated segmentation of WMA provides a better account than the visual Fazekas and Wahlund scales of the decline in executive functions and processing speed in stroke patients. METHODS: The analyses were conducted on the 358 patients of the GRECogVASC cohort with an MRI performed at six months poststroke in the Amiens center. WMA were visually analyzed using the Fazekas (subcortical abnormalities) and Wahlund scales. Segmentation was performed using LST (3.0.3). Following preliminary studies to determine the optimal segmentation threshold, we examined the relationship between cognitive status and WMA volume computed at each threshold using receiver operating characteristic (ROC) curves. Finally, we assessed the ability of both Fazekas and Wahlund visual scores and WMA volume to account for cognitive scores by using a bivariate Pearson correlation analysis, comparing correlation coefficients with the Fisher transformation and repeating correlation analysis after adjustment for the lesion volume. RESULTS: Increasing the threshold led to an underestimation of WMA (P=0.0001) (significant for a threshold ≥0.2) and an improvement in correct rejection of signal changes in the stroke cavity (P=0.02) (significant for a threshold ≤0.5), susceptibility artifacts (P=0.002) (significant for a threshold ≤0.6), and corticospinal degeneration (P=0.03) (significant for a threshold ≤0.5). WMA volume decreased with increasing threshold (P=0.0001). Areas under the curve (AUC) did not differ according to the threshold (processing speed: P=0.85, executive cognitive functions: P=0.7). Correlation coefficients between cognitive scores and WMA were higher for WMA volume than the Fazekas (processing speed: Z=-3.442, P=0.001; executive functions: Z=-2.751, P=0.006) and Wahlund scores (processing speed: Z=-3.615, P=0.0001; executive functions: Z=-2.769, P=0.006). Adjustment for lesion volume did not alter the correlations with WMA volume (processing speed: r=-0.327 [95%CI: -0.416; -0.223], P=0.0001; executive functions: r=-0.262 [95%CI: -0.363; -0.150], P=0.0001). CONCLUSION: This study shows that WMA volume assessed by automated segmentation provides a better account of cognitive disorders than visual analysis. This should favor its wider use to refine imaging determinants of poststroke cognitive disorders.

Detection of allele-specific expression in spatial transcriptomics with spASE.

Spatial transcriptomics technologies permit the study of the spatial distribution of RNA at near-single-cell resolution genome-wide. However, the feasibility of studying spatial allele-specific expression (ASE) from these data remains uncharacterized. Here, we introduce spASE, a computational framework for detecting and estimating spatial ASE. To tackle the challenges presented by cell type mixtures and a low signal to noise ratio, we implement a hierarchical model involving additive mixtures of spatial smoothing splines. We apply our method to allele-resolved Visium and Slide-seq from the mouse cerebellum and hippocampus and report new insight into the landscape of spatial and cell type-specific ASE therein.

Pyritic stromatolites from the Paleoarchean Dresser Formation, Pilbara Craton: Resolving biogenicity and hydrothermally influenced ecosystem dynamics.

This study investigates the paleobiological significance of pyritic stromatolites from the 3.48 billion-year-old Dresser Formation, Pilbara Craton. By combining paleoenvironmental analyses with observations from well-preserved stromatolites in newly obtained drill cores, the research reveals stratiform and columnar to domal pyritic structures with wavy to wrinkly laminations and crest thickening, hosted within facies variably influenced by syn-depositional hydrothermal activity. The columnar and domal stromatolites occur in strata with clearly distinguishable primary depositional textures. Mineralogical variability and fine-scale interference textures between the microbialites and the enclosing sediment highlight interplays between microbial and depositional processes. The stromatolites consist of organomineralization - nanoporous pyrite and microspherulitic barite - hosting significant thermally mature organic matter (OM). This includes filamentous organic microstructures encased within nanoporous pyrite, resembling the extracellular polymeric substance (EPS) of microbes. These findings imply biogenicity and support the activity of microbial life in a volcano-sedimentary environment with hydrothermal activity and evaporative cycles. Coupled changes in stromatolite morphology and host facies suggest growth in diverse niches, from dynamic, hydrothermally influenced shallow-water environments to restricted brine pools strongly enriched in SO 4 2 - $$ {\mathrm{SO}}_4^{2-} $$ from seawater and hydrothermal activity. These observations, along with S stable isotope data indicating influence by S metabolisms, and accumulations of biologically significant metals and metalloids (Ni and As) within the microbialites, help constrain microbial processes. Columnar to domal stromatolites in dynamic, hydrothermally influenced shallow water deposits likely formed by microbial communities dominated by phototrophs. Stratiform pyritic structures within barite-rich strata may reflect the prevalence of chemotrophs near hydrothermal venting, where hydrothermal activity and microbial processes influenced barite precipitation. Rapid pyrite precipitation, a putative taphonomic process for preserving microbial remnants, is attributed to microbial sulfate reduction and reduced S sourced from hydrothermal activity. In conclusion, this research underscores the biogenicity of the Dresser stromatolites and advances our understanding of microbial ecosystems in Earth's early history.

A systematic review of the nature and efficacy of Rational Emotive Behaviour Therapy interventions.

In the absence of a single comprehensive systematic review of Rational Emotive Behaviour Therapy interventions across all settings, we reviewed the methodological quality, effectiveness and efficacy of Rational Emotive Behaviour Therapy interventions on irrational/rational beliefs. We explored the impact of Rational Emotive Behaviour Therapy on wider outcomes (e.g., mental health) and identified the characteristics of successful interventions. PsycARTICLES, PsycINFO, Scopus, SPORTDiscus, and PubMed were systematically searched up to December 2023 with 162 Rational Emotive Behaviour Therapy intervention studies identified which included a validated measure of irrational/rational beliefs. Where possible, effect size for irrational/rational belief change was reported and data was analysed through a qualitative approach. Using the Mixed Methods Appraisal tool, methodological quality within the Sport and Exercise domain was assessed as good, whilst all other domains were considered low in quality, with insufficient detail provided on intervention characteristics and delivery. Most studies were conducted in the United States, within the Education domain, and assessed irrational beliefs in non-clinical adult samples. Overall, studies reported significant reductions in irrational beliefs, increases in rational beliefs and improvements in mental health outcomes (e.g., depression). More successful interventions were delivered by trained Rational Emotive Behaviour Therapy practitioners, adopted the ABC framework and were longer in duration. We highlight the importance of designing and conducting rigorous future Rational Emotive Behaviour Therapy research to generate clearer insights as to its impact on irrational/rational beliefs and mental health outcomes.

Clinical assessment of breastfeeding in preterm infants.

Breastmilk confers empirical benefits for preterm infants, however direct breastfeeding rates in this population remain low. For preterm infants, it may be useful to assess the volume of breastmilk transferred from mother to baby when breastfeeding, particularly during transition to oral feeding when breastfeeding attrition is high. Establishing breastfeeding in preterm infants is complex and without knowledge of milk intake during breastfeeds there is risk of inaccurate feed supplementation with subsequent effects on growth and nutrition. Here we review the evidence for clinical assessments of breastfeeding in preterm infants including test weighing, use of isotope labelled water and clinical observation tools designed to estimate adequacy of breastfeeds. Test weighing is a validated measurement, however requires rigorous protocols and further investigation in small infants. Use of isotope labelled water is a validated technique but, due to sampling requirements, reflects intake over days and weeks instead of individual feeds. Clinical observation tools assessed in preterm infants, have not been shown to reflect volumes of breastmilk intake. While current methods have limitations, the goal is to identify measurement tools to be used as temporary aids to facilitate transition to direct breastfeeding while minimising risk of inaccurate supplementation.

The Effect of Duration on Performance and Perceived Fatigability During Acute High-Intensity Interval Exercise in Young, Healthy Males and Females.

Few studies have explored the kinetics of performance and perceived fatigability during high-intensity interval training, despite its popularity. We aimed to characterize the kinetics of fatigability and recovery during an 8 × 4-min HIIT protocol, hypothesizing that most muscle function impairment would occur during the initial four intervals. Fifteen healthy males and females (mean ± standard deviation; age = 26 ± 5 years, V̇O2max = 46.8 ± 6.1 mL·kg-1·min-1) completed eight, 4-min intervals at 105% of critical power with 3 min of rest. Maximal voluntary knee extension contractions (MVCs) coupled with electrical nerve stimulation were performed at baseline and after the first, fourth, and eighth intervals. MVC, potentiated twitch force (Pt), and Db10:100 ratio all declined throughout HIIT (p < 0.05). MVC sharply declined after interval 1 (-15 ± 9% relative to baseline; p < 0.05) and had only further declined after interval 8 (-26 ± 11%; p < 0.05), but not interval 4 (-19 ± 13%; p > 0.05). Pt and Db10:100 also sharply declined after interval 1 (Pt: -18 ± 13%, Db10:100: -14 ± 20%; p < 0.05) and further declined after interval 4 (Pt: -35 ± 19%, Db10:100: -30 ± 20%; p < 0.05) but not interval 8 (Pt: -41 ± 19%; Db10:100: -32 ± 18%; p > 0.05). Voluntary activation did not significantly change across the HIIT protocol (p > 0.05). Evoked force recovery was significantly blunted as more intervals were completed: after interval 1, Pt recovered by 7 ± 11% compared to -6 ± 7% recovery after interval 8 (p < 0.05). Ratings of perceived effort, fatigue, and leg pain rose throughout the session (p < 0.05 for each) and were greater (effort and fatigue) for females (p < 0.05). Otherwise, males and females exhibited similar performance fatigability kinetics, with contractile function declines blunted in response to additional intervals.

Patient-reported outcomes in neuro-oncology.

PURPOSE OF REVIEW: To provide up-to-date evidence on patient-reported outcomes (PROs) in neuro-oncology, with a focus on the core constructs of health-related quality of life (HRQoL) and the use of PROs in clinical trials and clinical practice.[Supplemental Digital Content: Video Abstract PROs in Neuro-Oncology.mov]. RECENT FINDINGS: PROs are gaining importance in brain tumor research and medical care. For patients with a brain tumor, core PRO constructs are pain, difficulty communicating, perceived cognition, seizures, symptomatic adverse events, physical functioning and role and social functioning, which are assessed through patient-reported outcome measures (PROMs). Initiatives have been taken to improve the reliability and robustness of PRO data, including standardization of items included in clinical trial protocols (the SPIRIT-PRO extension) and formulation of PRO priority objectives for use in clinical trials (the SISAQOL-Innovative Medicines Initiative). In brain tumor patients with cognitive impairment, caregiver-reported outcomes may complement or replace PROs to increase accuracy. The next key challenge will be to widely implement PROs and apply PRO data in clinical practice to benefit patients with brain tumors. SUMMARY: PROs are clinically relevant endpoints providing information only known by the patient. Standardization of the use of PROs in clinical trials and wide implementation in clinical practice is needed to improve HRQoL of brain tumor patients.

Secondhand Nicotine Absorption From E-Cigarette Vapor vs Tobacco Smoke in Children.

Importance: With the prevalence of e-cigarette use (vaping) increasing worldwide, there are concerns about children's exposure to secondhand vapor. Objective: To compare nicotine absorption among children who are (1) exposed to secondhand tobacco smoke only or (2) exposed to secondhand vapor only with (3) those exposed to neither. Design, Setting, and Participants: The US Continuous National Health and Nutrition Examination Survey (NHANES) is a repeat cross-sectional survey. Participants are interviewed in their homes and, several days after, visit a mobile examination center to provide biological specimens. This study uses data from a nationally representative sample of US households from 2017 to 2020. Participants were children aged 3 to 11 years with serum cotinine levels incompatible with current firsthand nicotine use (ie, <15 µg/L). The final analysis was conducted on January 9, 2024. Exposures: Reported exposure to secondhand smoke or vapor indoors in the past 7 days (only secondhand smoke, only secondhand vapor, or neither). Covariates included age, sex, ethnicity, family income, body weight, and height. Main Outcomes and Measures: The primary outcome was serum cotinine concentration, an objective biomarker of nicotine absorption. Geometric mean cotinine levels and 95% CIs were calculated using log-normal tobit regression, accounting for the complex survey design and weights. Results: The mean (SD) age of the 1777 children surveyed was 7.4 (2.6) years, 882 (49.6%) were female, and 531 (29.9%) had family incomes below the poverty level. Nicotine absorption, as indexed by serum cotinine level, was highest among children only exposed to secondhand smoke (0.494 µg/L µg/L; 95% CI, 0.386-0.633 µg/L), followed by those exposed only to secondhand vapor (0.081 µg/L; 95% CI, 0.048-0.137 µg/L), equating to 83.6% (95% CI, 71.5%-90.5%; P < .001) lower nicotine absorption. Among children with no reported secondhand exposure, the geometric mean cotinine level was 0.016 µg/L (95% CI, 0.013-0.021 µg/L), or 96.7% (95% CI, 95.6%-97.6%; P < .001) lower than for those with exposure to secondhand smoke. Results were similar after covariate adjustment. Conclusions and Relevance: In this cross-sectional study of US children, nicotine absorption was much lower in children who were exposed to secondhand vapor vs secondhand smoke, but higher than in those exposed to neither. These findings suggest that switching from smoking to vaping indoors may substantially reduce, but not eliminate, children's secondhand exposure to nicotine and other noxious substances.

Compatibility of Generalized Noisy Qubit Measurements.

It is a crucial feature of quantum mechanics that not all measurements are compatible with each other. However, if measurements suffer from noise they may lose their incompatibility. Here, we consider the effect of white noise and determine the critical visibility such that all qubit measurements, i.e., all positive operator-valued measures (POVMs), become compatible, i.e., jointly measurable. In addition, we apply our methods to quantum steering and Bell nonlocality. We obtain a tight local hidden state model for two-qubit Werner states of visibility 1/2. This determines the exact steering bound for two-qubit Werner states and also provides a local hidden variable model that improves on previously known models. Interestingly, this proves that POVMs are not more powerful than projective measurements to demonstrate quantum steering for these states.

Evidence of thermophilization in Afromontane forests.

Thermophilization is the directional change in species community composition towards greater relative abundances of species associated with warmer environments. This process is well-documented in temperate and Neotropical plant communities, but it is uncertain whether this phenomenon occurs elsewhere in the tropics. Here we extend the search for thermophilization to equatorial Africa, where lower tree diversity compared to other tropical forest regions and different biogeographic history could affect community responses to climate change. Using re-census data from 17 forest plots in three mountain regions of Africa, we find a consistent pattern of thermophilization in tree communities. Mean rates of thermophilization were +0.0086 °C·y-1 in the Kigezi Highlands (Uganda), +0.0032 °C·y-1 in the Virunga Mountains (Rwanda-Uganda-Democratic Republic of the Congo) and +0.0023 °C·y-1 in the Udzungwa Mountains (Tanzania). Distinct from other forests, both recruitment and mortality were important drivers of thermophilzation in the African plots. The forests studied currently act as a carbon sink, but the consequences of further thermophilization are unclear.