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Knowing the genes involved in quantitative traits provides an entry point to understanding the biological bases of behavior, but there are very few examples where the pathway from genetic locus to behavioral change is known. To explore the role of specific genes in fear behavior, we mapped three fear-related traits, tested fourteen genes at six quantitative trait loci (QTLs) by quantitative complementation, and identified six genes. Four genes, Lamp, Ptprd, Nptx2, and Sh3gl, have known roles in synapse function; the fifth, Psip1, was not previously implicated in behavior; and the sixth is a long non-coding RNA, 4933413L06Rik, of unknown function. Variation in transcriptome and epigenetic modalities occurred preferentially in excitatory neurons, suggesting that genetic variation is more permissible in excitatory than inhibitory neuronal circuits. Our results relieve a bottleneck in using genetic mapping of QTLs to uncover biology underlying behavior and prompt a reconsideration of expected relationships between genetic and functional variation.

Abstract Background Retrospective and descriptive molecular epidemiology studies have shown that Mycobacterium tuberculosis whole genome sequencing can identify outbreaks and disease transmission events with higher resolution than conventional epidemiological investigations. Those studies have strengthened our understanding of genomic polymorphisms correlating with person-to-person transmission and helped resolve putative transmission clusters. To date, systematic genomic surveillance programs implemented for M. tuberculosis were only implemented in low-incidence settings. The purpose of this study is to determine whether there is an impact of routine M. tuberculosis whole genome sequencing on tuberculosis case detection in a high-incidence setting. Methods A cluster randomized controlled trial will be performed. Forty-eight rural village groups (or Fokontany) in the Vohibato district of Madagascar will be randomized to one of three interventions arms. Arm 1 (standard of care) involves healthcare facility-based passive case detection with smear microscopy testing. Arm 2 (best practice) consists of active case finding and Xpert MTB/RIF Ultra PCR testing followed by household contact investigations. Arm 3 (novel intervention) includes the same interventions as arm 2, with addition of sputum culture and M. tuberculosis whole genome sequencing for all newly diagnosed cases. In arm 3, molecular suggested putative outbreaks are investigated, and additional TB suspects are appropriately tested. The intervention observational period will be 2 years. The primary outcome will be the number of detected cases/100,000/year in each arm after 1 year of intervention. Discussion This study is designed to determine whether there is an impact of prospective whole genome sequencing-based molecular typing on tuberculosis case detection in high-incidence settings. Investigating potential outbreaks and focusing active case finding in spatiotemporal settings where disease transmission is suggested by genomic typing is hypothesized to improve case detection in rural communities. Trial registration ClinicalTrials.gov NCT05406453 . Retrospectively registered on June 6, 2022.

Abstract Cough is a common and commonly ignored symptom of lung disease. Cough is often perceived as difficult to quantify, frequently self-limiting, and non-specific. However, cough has a central role in the clinical detection of many lung diseases including tuberculosis (TB), which remains the leading infectious disease killer worldwide. TB screening currently relies on self-reported cough which fails to meet the World Health Organization (WHO) accuracy targets for a TB triage test. Artificial intelligence (AI) models based on cough sound have been developed for several respiratory conditions, with limited work being done in TB. To support the development of an accurate, point-of-care cough-based triage tool for TB, we have compiled a large multi-country database of cough sounds from individuals being evaluated for TB. The dataset includes more than 700,000 cough sounds from 2,143 individuals with detailed demographic, clinical and microbiologic diagnostic information. We aim to empower researchers in the development of cough sound analysis models to improve TB diagnosis, where innovative approaches are critically needed to end this long-standing pandemic.

Abstract Background Implementation strategies targeting individual healthcare professionals and teams, such as audit and feedback, educational meetings, opinion leaders, and reminders, have demonstrated potential in promoting evidence-based nursing practice. This systematic review examined the effects of the 19 Cochrane Effective Practice and Organization Care (EPOC) healthcare professional-level implementation strategies on nursing practice and patient outcomes. Methods A systematic review was conducted following the Cochrane Handbook, with six databases searched up to February 2023 for randomized studies and non-randomized controlled studies evaluating the effects of EPOC implementation strategies on nursing practice. Study selection and data extraction were performed in Covidence. Random-effects meta-analyses were conducted in RevMan, while studies not eligible for meta-analysis were synthesized narratively based on the direction of effects. The quality of evidence was assessed using GRADE. Results Out of 21,571 unique records, 204 studies (152 randomized, 52 controlled, non-randomized) enrolling 36,544 nurses and 340,320 patients were included. Common strategies (> 10% of studies) were educational meetings, educational materials, guidelines, reminders, audit and feedback, tailored interventions, educational outreach, and opinion leaders. Implementation strategies as a whole improved clinical practice outcomes compared to no active intervention, despite high heterogeneity. Group and individual education, patient-mediated interventions, reminders, tailored interventions and opinion leaders had statistically significant effects on clinical practice outcomes. Individual education improved nurses’ attitude, knowledge, perceived control, and skills, while group education also influenced perceived social norms. Although meta-analyses indicate a small, non-statistically significant effect of multifaceted versus single strategies on clinical practice, the narrative synthesis of non-meta-analyzed studies shows favorable outcomes in all studies comparing multifaceted versus single strategies. Group and individual education, as well as tailored interventions, had statistically significant effects on patient outcomes. Conclusions Multiple types of implementation strategies may enhance evidence-based nursing practice, though effects vary due to strategy complexity, contextual factors, and variability in outcome measurement. Some evidence suggests that multifaceted strategies are more effective than single component strategies. Effects on patient outcomes are modest. Healthcare organizations and implementation practitioners may consider employing multifaceted, tailored strategies to address local barriers, expand the use of underutilized strategies, and assess the long-term impact of strategies on nursing practice and patient outcomes. Trial registration PROSPERO CRD42019130446.

Peatland pools are unvegetated, inundated depressions that cover up to 30 % of the surface of many temperate and boreal peatlands and that are net carbon (C) sources within C-accumulating ecosystems. The emission of carbon dioxide (CO2) and methane (CH4) from peatland pools comes from the degradation of organic matter (OM) that comprises the surrounding matrix. It is, however, not clear how decomposition rates in pools, which define their function and distinguish them from other aquatic ecosystems, vary spatially and what mechanisms drive these variations. We first quantified rates of OM decomposition from fresh litter at different depths in six pools of distinct morphological characteristics in a temperate ombrotrophic peatland using litterbags of Sphagnum capillifolium and Typha latifolia over a 27-month period. Rates of decomposition were faster for T. latifolia than S. capillifolium and, overall, faster at the pool surface and decreased with increasing depth. We then measured potential CO2 and CH4 production from the sediments of the same six pools by performing 35 d laboratory incubations. Pool sediment chemistry was variable among pools and influenced the production of CH4 and CO2 from sediments, with decreasing CO2 production with increasing OM humification and decreasing CH4 production with increasing nitrogen-to-phosphorus ratio. Both CH4 production and CO2 production from pool sediments were higher in the 1 m deep pools but similar in the shallow < 1 and the > 1.5 m deep pools. When combining both experiments, our results indicate that OM decomposition in peatland pools is highly variable and mostly related to the environmental conditions in which it occurs as a function of general pool depth rather than to OM chemistry. Overall, we show that OM degradation and C emissions in peatland open-water pools may increase over time in warmer and drier climate conditions.

Quantification of potassium (K) excretion in dairy cattle is important to understand the environmental impact of dairy farming. To improve and monitor the environmental impact of dairy cows, there is a need for a simple, inexpensive, and less laborious method to quantify K excretion on dairy farms. The adoption of empirical mathematical models has been shown to be a promising tool to address this issue. Thus, the current study aimed to develop empirical predictive models for K excretion in dairy cattle from urine and feces that can help evaluate efficiency and monitor the environmental impact of milk production. To develop urine K (KUr, g/d) and fecal K (KFa, g/d) excretion prediction models, published literature that involved 45 and 54 treatment means from 10 and 14 studies, respectively, were used. Some studies reported either urinary or fecal K excretion or both, but in total, treatment means used to develop the models were from 17 studies. The linear mixed models were fitted with the fixed effect of K intake, DMI, dietary K content, urine volume, milk yield, and water intake, and the random effect of study weighted according to the number of observations. Leave-one-study out cross-validation was used to evaluate the performance of the proposed models and the best model was based on the lowest root mean square prediction error as a percentage of the observed mean values (RMSPE%) and highest concordance correlation coefficient (CCC). As expected, most daily K excretion was through urine (202.5 ± 92.1 g/d) than through feces (43.5 ± 21.0 g/d), and among the proposed models, the model including dietary K concentration showed poor predictive ability for both KUr and KFa with the lowest CCC values (−0.15 and −0.02, respectively) and systematic bias. The model developed using DMI to predict KFa excretion showed reasonable accuracy, as indicated by RMSPE, CCC, and R2marginal of 46.6%, 0.42, and 48%, respectively. Among the proposed models for KUr and KFa, the model with K intake demonstrated better predictive performance, showing minimal systematic bias and random errors due to data variability of >92%. While these proposed models suggested that reducing K intake can lead to a decrease in K excretion, it is important to ensure that dairy cows receive adequate amounts of this nutrient to maintain optimal health and productivity, especially during periods of heat stress.

Abstract Tuberculosis, caused by Mycobacterium tuberculosis, remains a major public health concern, demanding new antibiotics with innovative therapeutic principles due to the emergence of resistant strains. Benzothiazinones (BTZs) have been developed to address this problem. However, an unprecedented in vivo biotransformation of BTZs to hydride-Meisenheimer complexes has recently been discovered. Herein, we present a study of the influence of electron-withdrawing groups on the propensity of HMC formation in whole cells for a series of C-6-substituted BTZs obtained through reductive fluorocarbonylation as a late-stage functionalization key step. Gibbs free energy of reaction and Mulliken charges and Fukui indices on C-5 at quantum mechanics level were found as good indicators of in vitro HMC formation propensity. These results provide a first blueprint for the evaluation of HMC formation in drug development and set the stage for rational pharmacokinetic optimization of BTZs and similar drug candidates.

Introduction: Eye-tracking offers a distinctive opportunity to assess nurses’ clinical decision-making in simulation. Although its feasibility has been established in various scenarios, most studies have focused on a single participant, typically a physician in a leadership role. The application of eye-tracking in the challenging context of in-hospital cardiac arrest (IHCA) simulations, where nurses juggle diverse roles and undertake physical tasks such as chest compressions, has yet to be explored.Objectives: This study aimed to assess the feasibility and acceptability of eye-tracking with nurses’ during IHCA simulations. Additionally, the study aimed to describe eye-tracking metrics based on different resuscitation roles and to explore the relationship between eye-tracking metrics to pinpoint the most informative metrics for the design of future studies.Methods: In this single-group observational study, 56 newly hired nurses wore eye-tracking glasses during IHCA simulations. The primary feasibility criterion was the proportion of usable eye-tracking data. Secondary criteria included recruitment rate, calibration time, and glasses acceptability. The relationship among eye-tracking metrics was investigated through correlation analyses.Results: Calibration of the devices was rapid, and 85.7% of the data was usable. The glasses were comfortable, non-distracting, and did not impede nurses’ vision or performance. Data were mapped for five areas of interest: the patient’s head and chest, cardiac monitor, teammates, and resuscitation cart. Eye-tracking metrics exhibited variations based on resuscitation roles. Fixation count, fixation duration, and time to first fixation appeared to be the most informative metrics in IHCA simulation.Discussion and conclusion: These findings demonstrate the feasibility and acceptability of analyzing nurses’ eye-tracking data during IHCA simulations using a role-based approach. Future research should explore correlations with additional attention measures to enhance our understanding of nurse decision-making during cardiac arrest and improve educational strategies and outcomes.

The transcription factor receptor‐interacting protein 140 (RIP140) regulates intestinal homeostasis and tumorigenesis through Wnt signaling. In this study, we investigated its effect on the Notch/HES1 signaling pathway. In colorectal cancer (CRC) cell lines, RIP140 positively regulated HES1 gene expression at the transcriptional level via a recombining binding protein suppressor of hairless (RBPJ)/neurogenic locus notch homolog protein 1 (NICD)‐mediated mechanism. In support of these in vitro data, RIP140 and HES1 expression significantly correlated in mouse intestine and in a cohort of CRC samples, thus supporting the positive regulation of HES1 gene expression by RIP140. Interestingly, when the Notch pathway is fully activated, RIP140 exerted a strong inhibition of HES1 gene transcription controlled by the level of HES1 itself. Moreover, RIP140 directly interacts with HES1 and reversed its mitogenic activity in human CRC cells. In line with this observation, HES1 levels were associated with a better patient survival only when tumors expressed high levels of RIP140. Our data identify RIP140 as a key regulator of the Notch/HES1 signaling pathway, with a dual effect on HES1 gene expression at the transcriptional level and a strong impact on colon cancer cell proliferation.

To identify addiction genes, we evaluate intravenous self-administration of cocaine or saline in 84 inbred and recombinant inbred mouse strains over 10 days. We integrate the behavior data with brain RNA-seq data from 41 strains. The self-administration of cocaine and that of saline are genetically distinct. We maximize power to map loci for cocaine intake by using a linear mixed model to account for this longitudinal phenotype while correcting for population structure. A total of 15 unique significant loci are identified in the genome-wide association study. A transcriptome-wide association study highlights the Trpv2 ion channel as a key locus for cocaine self-administration as well as identifying 17 additional genes, including Arhgef26, Slc18b1, and Slco5a1. We find numerous instances where alternate splice site selection or RNA editing altered transcript abundance. Our work emphasizes the importance of Trpv2, an ionotropic cannabinoid receptor, for the response to cocaine.

Mendelian randomization (MR) has emerged as a powerful approach to leverage genetic instruments to infer causality between pairs of traits in observational studies. However, the results of such studies are susceptible to biases owing to weak instruments, as well as the confounding effects of population stratification and horizontal pleiotropy. Here, we show that family data can be leveraged to design MR tests that are provably robust to confounding from population stratification, assortative mating, and dynastic effects. We show in simulations that our approach, MR-Twin, is robust to confounding from population stratification and is not affected by weak instrument bias, whereas standard MR methods yield inflated false positive rates. We then conduct an exploratory analysis of MR-Twin and other MR methods applied to 121 trait pairs in the UK Biobank data set. Our results suggest that confounding from population stratification can lead to false positives for existing MR methods, whereas MR-Twin is immune to this type of confounding, and that MR-Twin can help assess whether traditional approaches may be inflated owing to confounding from population stratification.

Purpose: Fertility issues are of great concern for young women undergoing treatment for breast cancer (BC). Fertility preservation (FP) protocols using controlled ovarian stimulation (COS) with letrozole have been widely used with overall good results. However, letrozole cannot be used in every country in this context. This study aimed to assess the efficacy of tamoxifen for COS in women with early BC undergoing FP. Methods: This multicentric prospective study included patients aged 18–40, diagnosed with stage I, II and III invasive BC, undergoing tamoxifen-COS before adjuvant or neoadjuvant chemotherapy (NAC). The primary endpoint was the efficacy of tamoxifen-COS protocol evaluated by the number of oocytes collected and vitrified. Secondary endpoints included the time interval before chemotherapy, breast cancer (BC) recurrence rates, and reproductive outcomes. Results: Ninety-five patients were included between 2014 and 2017, aged 31.5 ± 4 years on average. 37.9 % received NAC and 62.1 % received adjuvant chemotherapy. FP procedure was successful in 89.5 % of the cycles. The mean number of collected and vitrified oocytes was 12.8 ± 7.9 and 9.8 ± 6.2, respectively. The mean duration of COS was 10.4 ± 1.9 days. Median time before chemotherapy initiation was 3.6 weeks (IQR 3.1; 4.1) for women receiving NAC. Five-year relapse-free and overall survival rates were in-line with those expected in this population. Twenty-one women had spontaneous full-term pregnancies, while 5 underwent IVF cycles with frozen-thawed oocytes, without pregnancy. Conclusion: Tamoxifen-COS protocols appear to be feasible before adjuvant or NAC treatment in young BC patients and efficient in terms of oocyte yield.

Background: The major drivers of carbon dioxide (CO2eq) emissions of external beam radiation therapy (EBRT) are not well known and limit our ability to initiate mitigation strategies. Material and methods: We describe the carbon footprint of four typical centers. We explore direct EBRT associated factors such as the impact of fractionation and use of MRI-LINAC, as well as indirect factors (e.g. patient rides). Treatment strategy related CO2eq emissions are included in a health technology assessment analysis that takes into account CO2eq emissions. Results: A typical EBRT treatment emits from 185 kgCO2eq to 2066 kgCO2eq. CO2eq emissions are mostly driven by (i) accelerator acquisition and maintenance (37.8 %), (ii) patients and workers rides (32.7 %), (iii) drugs and medical devices (7.3 %), (iv) direct energy consumption (6.1 %), and (v) building and bunker construction (5.6 %) with a substantial heterogeneity among centers. Hypofractionation has a strong impact to mitigate emissions. MRI-LINAC is associated with a substantial increase in CO2eq emissions per fraction and requires ultra hypofractionation in 5 fractions to achieve a similar carbon footprint compared to 20 fractions treatment schemes. The expected limited small increase in toxicities due to hypofractionation (when existing) are in the same range as avoided detrimental effects to future people’s health thanks to CO2eq mitigation. Conclusion: Carbon footprint of EBRT is not neglectable and could be mitigated. When safely feasible, hypofractionation is one of the main factors to decrease this impact. Taking into account CO2eq emissions has a substantial impact on the health technology assessment of EBRT, favoring hypofractionated regimens.

ABSTRACT: Net energy for lactation (NEL) and metabolizable protein (MP) are the 2 main nutritional forces that drive synthesis of milk components. This study investigated mammary-gland metabolism in dairy cows in response to variations in the supply of NEL and MP. Four Holstein dairy cows were randomly assigned to a 4 × 4 Latin square design, in which each experimental period consisted of 14 d of dietary treatment. The diets provided 2 levels of NEL (low energy, 25.0 Mcal/d vs. high energy, 32.5 Mcal/d) and 2 levels of MP (low protein, 1,266 g/d vs. high protein, 2,254 g/d of protein digestible in the intestine) in a 2 × 2 factorial arrangement. Performance and dry matter intake (DMI) were measured during the last 5 d of each period, and the mammary net balance was measured on d 13 by collecting 6 sets of blood samples from the left carotid artery and left mammary vein. Mammary plasma flow was measured according to the Fick principle for Phe and Tyr. The mammary net balance of carbon equaled the uptake of nutrients expressed as carbon minus the output of lactose, fatty acids (FA) synthesized in the mammary gland, AA of milk protein, and glycerol-3P from triglyceride on d 13. Milk, lactose, fat, and protein yields increased when NEL and MP supplies increased. However, increasing the NEL supply increased FA synthesis more than increasing the protein supply did. In addition, FA secretion increased more than lactose secretion when the NEL supply increased. Increasing the NEL supply increased the left half-udder uptake of all major energy-yielding nutrients by increasing mammary plasma flow. However, nutrient uptake increased more than milk output did, which in turn increased carbon dioxide output. This increase in nutrient oxidation by the mammary gland decreased the mammary efficiency of nutrients utilization when the NEL supply increased. Increasing MP supply tended to increase glucose uptake through mammary clearance and increased mammary AA uptake with no change in mammary plasma flow. In addition, the protein supply did not change the mammary uptake of acetate or β-hydroxybutyrate. The increase in milk-component secretions in response to either NEL or MP supplies occurred through different metabolic adaptations (increase in mammary plasma flow vs. clearances, respectively). These results suggest that the nutrient use by the mammary gland is highly flexible, which helps in maintaining milk and milk-component yields even with limiting nutrient supplies.

Abstract Cannabis sativa L., previously concealed by prohibition, is now a versatile and promising plant, thanks to recent legalization, opening doors for medical research and industry growth. However, years of prohibition have left the Cannabis research community lagging behind in understanding Cannabis genetics and trait inheritance compared to other major crops. To address this gap, we conducted a comprehensive genome-wide association study (GWAS) of nine key agronomic and morphological traits, using a panel of 176 drug-type Cannabis accessions from the Canadian legal market. Utilizing high-density genotyping-by-sequencing (HD-GBS), we successfully generated dense genotyping data in Cannabis, resulting in a catalog of 800 K genetic variants, of which 282 K common variants were retained for GWAS analysis. Through GWAS analysis, we identified 18 markers significantly associated with agronomic and morphological traits. Several identified markers exert a substantial phenotypic impact, guided us to putative candidate genes that reside in high linkage-disequilibrium (LD) with the markers. These findings lay a solid foundation for an innovative cannabis research, leveraging genetic markers to inform breeding programs aimed at meeting diverse needs in the industry.

Le partage de l’espace et la cohabitation sociale dans les grandes villes sont soumis à différents diktats. Entre la spéculation immobilière, la revitalisation, la densification et les mouvements de populations, ce partage est souvent bousculé. Ce que les études démontrent jusqu’à maintenant c’est un partage inégal de cet espace au détriment des populations marginalisées, surtout des populations en situation d’itinérance. Pour être attractives, les villes repoussent les populations perçues comme étant indésirables au regard des activités commerciales et touristiques. Les populations en situation d’itinérance voient donc leur accès à la ville compromis principalement en raison de leur occupation de l’espace public jugée comme étant fautive. Ces populations n’ont nulle part où aller, nulle part pour disparaître. En parallèle, en matière de prise en charge des populations en situation d’itinérance, le logement est souvent placé comme la pierre angulaire de toutes les démarches d’intervention et c’est à partir du logement qu’est donc pensée la réinsertion sociale (de manière micro-sociologique) ou encore la réduction des inégalités sociales (de manière macro-sociologique). Par ailleurs, de nombreuses villes occidentales, comme Montréal (Québec, Canada) connaissent d’importantes crises du logement, rendant l’accès à ceux-ci plus difficile que jamais. Est-il alors possible, d’exister, d’utiliser, de circuler, de se rencontrer dans l’espace, sans avoir d’ancrage à un logement? Cet article cherche à revoir, de manière inédite, les pratiques qui s’interrogent sur le vivre-ensemble, sur la cohabitation sociale, afin d’identifier celles qui contribuent davantage au bien-être des personnes en situation d’itinérance. C’est plus particulièrement en recourant aux pratiques d’aménagement (architecture, design, urbanisme) et aux pratiques d’intervention sociale (travail social, médiation, soin) que nous tenterons de déplacer notre regard pour favoriser un meilleur partage des espaces urbains.

ABSTRACT: Adequate prediction of postruminal outflow of protein fractions is the starting point for the determination of metabolizable protein supply in dairy cows. The objective of this meta-analysis was to compare the performance of 3 dairy feed evaluation systems (National Research Council [NRC], Cornell Net Protein and Carbohydrate System [CNCPS], and National Academies of Sciences, Engineering and Medicine [NASEM]) to predict outflows (g/d) of nonammonia nitrogren (NAN), microbial N (MiN), and nonammonia nonmicrobial N (NANMN). Predictions of rumen degradabilities (% of nutrient) of protein (RDP), NDF, and starch were also evaluated. The data set included 1,294 treatment means from 312 digesta flow studies. The 3 feed evaluation systems were compared using the concordance correlation coefficient (CCC), the ratio of root mean square prediction error (RMSPE) on standard deviation of observed values (RSR), and the slope between observed and predicted values. Mean and linear biases were deemed biologically relevant and are discussed if higher than a threshold of 5% of the mean of observed values. The comparisons were done on observed values adjusted or not for the study effect; the adjustment had a small effect on the mean bias but the linear bias reflected a response to a dietary change rather than absolute predictions. For the absolute predictions of NAN and MiN, CNCPS had the best-fit statistics (8% greater CCC; 6% lower RMSPE) without any bias; NRC and NASEM underpredicted NAN and MiN, and NASEM had an additional linear bias indicating that the underprediction of MiN increased at increased predictions. For NANMN, fit statistics were similar among the 3 feed evaluation systems with no mean bias; however, the linear bias with NRC and CNCPS indicated underprediction at low predictions and overprediction at elevated predictions. On average, the CCC were smaller and RSR ratios were greater for MiN versus NAN indicating increased prediction errors for MiN. For NAN responses to a dietary change, CNCPS also had the best predictions, although the mean bias with NASEM was not biologically relevant and the 3 feed evaluation systems did not present a linear bias. However, CNCPS, but not the 2 other feed evaluation systems, presented a linear bias for MiN, with responses being overpredicted at increased predictions. For NANMN, responses were overpredicted at increased predictions for the 3 feed evaluation systems, but to a lesser extent with NASEM. The site of sampling had an effect on the mean bias of MiN and NANMN in the 3 feed evaluation systems. The mean bias of MiN was higher in omasal than duodenal studies in the 3 feed evaluation systems (from 55 to 61 g/d) and this mean bias was twice as large when 15N labeling was used as a microbial marker compared with purines. Such a difference was not observed for duodenal studies. The reasons underlying these systematic differences are not clear as the type of measurements used in the current meta-analysis does not allow to delineate if one site or one microbial marker is yielding the “true” postruminal N outflows. Rumen degradabilities of protein was underpredicted with CNCPS, and RDP responses to a dietary change was underpredicted by the 3 feed evaluation systems with increased RDP predictions. Rumen degradability of NDF was underpredicted and had poor fit statistics for NASEM compared with CNCPS. Fit statistics were similar between CNCPS and NASEM for rumen degradability of starch, but with an underprediction of the response with NASEM and absolute values being overpredicted with CNCPS. Multivariate regression analyses showed that diet characteristics were correlated with prediction errors of N outflows in each feed evaluation system. Globally, compared with NAN and NANMN, residuals of MiN were correlated with several moderators in the 3 feed evaluation systems reflecting the complexity to measure and model this outflow. In addition, residuals of NANMN were correlated positively with RDP suggesting an overestimation of this parameter. In conclusion, although progress is still to be made to improve equations predicting postruminal N outflows, the current feed evaluation systems provide sufficient precision and accuracy to predict postruminal outflows of N fractions.

Abstract This study assesses the reliability and limitations of the Geostationary Lightning Mapper (GLM) in detecting continuing currents by comparing observations from ground‐based high‐speed cameras with GLM‐16 data. Our findings show that the GLM's one‐group detection efficiency (DE_1) is 53%, while the more stringent five‐consecutive‐group detection efficiency (DE_5) is 10%. Optical signals detected by the GLM predominantly occur during the early stages of continuing currents. Additionally, there is a notable disparity in detection efficiencies between positive and negative continuing currents, with positive continuing currents being detected more frequently. The application of the logistic regression model developed by Fairman and Bitzer (2022) further illustrates the limitations in continuing current identification. The study underscores the challenges of relying solely on satellite data to monitor and analyze continuing currents, emphasizing the need for advancements in detection technologies and methodologies to reliably detect continuing current at a large spatial scale.

La discapacidad en los pueblos indígenas es un tema que ha despertado un creciente interés en diversos estudios en Latinoamérica en los últimos años. Sin embargo, la forma de acercarse teóricamente a este campo no es unívoca. Este artículo pretende poner en discusión las distintas formas de aproximarse a la comprensión de la discapacidad en los pueblos indígenas, y así proponer que este vínculo puede darse de distintas maneras, de acuerdo con el posicionamiento epistemológico que sostenga la relación entre las culturas. Se reconoce, además, que estos enfoques tienen consecuencias tanto en la academia como en los territorios. Esta reflexión desarrollará siete formas de aproximación que sugieren un camino no necesariamente lineal, pero sí progresivo hacia la interculturalidad crítica como enfoque investigativo y activista en el campo de la discapacidad en los pueblos indígenas.

Increasing dietary Met, Lys, and His supply without increasing the dietary protein content was reported to partially alleviate the productive and physiological impact of heat stress. Nevertheless, the metabolic pathways involved are yet to be identified. Thus, we aimed to explore the metabolic pathways associated with these positive effects and develop new metabolomics-based hypotheses. Twelve lactating Holstein cows (primiparous, n = 6; multiparous, n = 6; 42.2 ± 10.6 kg/d milk yield; 83 ± 28 days in milk) were enrolled in two 3×3 replicated Latin squares consisting of 14-day treatment periods: heat stress [HS; max. Temperature Humidity Index (THI) 84, 16.8% crude protein (CP), 1,741 g/d metabolizable protein (MP), 108 Lys, 33 Met, and 37 His (g/d)], pair feeding in thermo-neutrality (TN; max. THI 64, same diet as HS), and HS with increased Lys, Met and His supply [HS+AA; max. THI 84; 17.0% CP, 1,730 g/d MP, 179 Lys, 58 Met, and 45 His (g/d)]. Blood plasma and milk were sampled on day 14 for metabolomics profiling. Several amino acids (AA) and derivatives differed between the treatments. Plasma and milk Met, Val, Trp and α-amino adipic acid concentrations were highest in HS+AA (false discovery rate-P (FDR) < 0.05). Moreover, only plasma Lys and milk His were highest in HS+AA (FDR < 0.05). Some phosphatidylcholines (PC) and diglycerides had lower concentrations in HS than TN (FDR < 0.05), while HS+AA had similar concentrations as TN. The pathway enrichment analysis revealed that the AA-related pathways were more significantly affected in multiparous than in primiparous cows. Our results suggest that increased supply of Met stimulated PC synthesis in HS+AA to similar concentrations as in TN. Increased Lys supply likely elevated the oxidation rate of Lys and downregulated the catabolism of other essential AA (EAA) such as Val and Trp, stimulating milk protein synthesis. No clear associations were found related to His availability. In conclusion, partial amelioration of productive and physiological effects of heat stress associated with increased dietary Met and Lys supply were likely explained by stimulated PC synthesis and increased plasma and milk concentrations of other EEA.

Objective: Poor distillation practices in the production of spirits have historically resulted in many instances of adverse health outcomes including death. Concern has focused on lead and copper contamination as well as unhealthy levels of methanol and glyphosate. This study assesses home-distilled and commercially distilled alcohols from Texas for these substances of concern, highlighting their potential risks to public health. Methods: Atomic absorption spectroscopy, gas chromatography, and enzyme-linked immunosorbent assay were employed to determine lead and copper, methanol, and glyphosate levels in 12 commercial and 36 home-distilled alcohol samples. Results: Our findings showed that 11 % of the home-distilled alcohols exceeded the U.S. Alcohol and Tobacco Tax and Trade Bureau's copper safety limits of 0.5 mg/L for wine. Additionally, 36 % of these samples surpassed the European Commission (EC)'s lead legal threshold of 0.15 mg/L set for wine products. Results from commercial alcohols indicated that no samples exceeded the same safety limits for copper, and 33 % exceeded the same legal threshold for lead. Both commercial and home-distilled alcohols exhibited methanol concentrations remarkably below the 0.35 % limit for brandy set by the U.S. Food and Drug Administration. Only two home-distilled samples contained detectable glyphosate concentrations well below 100 μg/L, the maximum residue level in beer and wine established by the EC. Conclusions: Our findings suggested that consumption of alcohol in Texas may pose potential health risks associated with the elevated content of lead and copper. There is a need for increased focus on alcohol as a potential source of exposure to heavy metals.

Dairy cattle excreta are a valuable source of orthophosphate (Ortho-P), an inorganic form of phosphorus (P) that is readily available for microorganisms, plant growth, and development. There is, however, a growing environmental concern about the potential negative environmental impact of excessive amounts of Ortho-P excretion, which can lead to the eutrophication of water bodies. As a result, the development of mathematical equations to quantify and manage Ortho-P excretion on dairy farms could prove valuable for environmental sustainability. This study aimed to use literature data to develop empirical predictions for Ortho-P (g/kg dry matter [DM]) excretion using total P (TP [g/kg DM]) content of dairy cattle feces (Ortho-Pf) and manure (Ortho-Pm). Data sets from studies that evaluated and characterized the different forms of P in feces and manure from dairy cattle were compiled. After outlier exclusion, the final retained database for feces included 37 treatment means from 4 published papers while the manure comprised 23 treatment means from 7 published papers. A linear-mixed model was used to develop the predictive equations, incorporating the random effect of the study. A leave-one-out cross-validation procedure was used to evaluate the predictive ability of the developed models, whereby studies were regarded as folds. The fecal equation was determined as Ortho-Pf (g/kg DM) = −2.447 (0.572) + 0.966 (0.083) × TP (g/kg DM) (R2 = 0.79) and resulted in a root mean square prediction error as a percentage of mean observed value (RMSPE, %) of 32.8% and error due to random sources of 97.6%. Additionally, the manure equation was determined as Ortho-Pm (g/kg) = −0.204 (0.446) + 0.590 (0.065) × TP (g/kg) (R2 = 0.77) and had an RMSPE of 43.3% with a random error of 93.9%. Both models revealed minimal mean and slope biases on feces and manure data. Findings suggest that these sets of equations can be used to estimate excreted Ortho-P from total excreted P, helping nutritionists and farmers to understand the impact of dietary P changes on the environment. Further, these equations can be incorporated into extant models such as the Cornell Net Carbohydrate and Protein System (CNCPS) to aid in understanding and mitigating P and Ortho-P excretion from dairy cattle and to clarify the portion of P that migrates more rapidly into watersheds.

Considering the harmful effects of cannabis on individuals with a severe mental disorder and the limited effectiveness of current interventions, this case report showcases the beneficial results of a 10-session Avatar intervention for cannabis use disorder (CUD) on a polysubstance user with a comorbid schizoaffective disorder. Virtual reality allowed the creation of an Avatar representing a person significantly related to the patient’s drug use. Avatar intervention for CUD aims to combine exposure, relational, and cognitive behavioral therapies while practicing real-life situations and learning how to manage negative emotions and cravings. Throughout therapy and later on, Mr. C managed to maintain abstinence from all substances. Also, an improvement in the severity of CUD, as well as a greater motivation to change consumption, was observed after therapy. As observed by his mother, his psychiatrist, and himself, the benefits of Avatar intervention for CUD extended to other spheres of his life. The drastic results observed in this patient could be promising as an alternative to the current treatment available for people with a dual diagnosis of cannabis use disorder and psychotic disorder, which generally lack effectiveness. A single-blind randomized control trial comparing the treatment with a classical intervention in a larger sample is currently underway to evaluate whether the results are reproducible on a larger sample.

Background/Objective: To address the opioid epidemic in Kansas City, Missouri, local health systems sought to implement a referral to peer recovery coaches (PRCs) for clients presenting with opioid use disorder. Client referrals were made primarily through health system emergency departments, where PRCs met clients to facilitate linkages to recovery support for up to twelve months. This study aimed to evaluate and improve program implementation with process mapping at three local health systems. Methods: Using a five-phase conceptual framework and three development and implementation domains, providers, administrators, and PRCs were interviewed to identify the process for recognizing clients with opioid use disorders and referring them to PRCs. Serial meetings were held to validate the process maps at three health systems and a distillation of key processes was created to guide future analyses and implementation efforts. Results: A detailed process map for each health system was developed, from which a high-level process map was created to support future implementation efforts. Health system-specific process maps varied, although conceptually coherent elements were identified across each system to diagram a recovery ecosystem to support client referrals to PRCs. Conclusions: By systematically assessing the implementation of the same program across different health systems, critical steps, along with their barriers and facilitators, were identified that can be used to understand the processes of care associated with outcomes and to guide future implementation efforts.

BackgroundHealth organizations face the critical task of executing and overseeing comprehensive health care. To address the challenges associated with this task, evidence-based dashboards have emerged as valuable tools. Since 2016, the regional health organizations of Quebec, Canada, have been responsible for ensuring implementation of the Quebec Alzheimer Plan (QAP), a provincial plan that aims to reinforce the capacity of primary care services to detect, diagnose, and treat persons with dementia. Despite the provincial scope of the QAP, the diverse material and human resources across regions introduce variability in the interest, utility, and specific needs associated with these dashboards. ObjectiveThe aim of this study was to assess the interest and utility of dashboards to support the QAP implementation, as well as to determine the needs for improving these aspects according to the perspectives of various types of professionals involved across regions. MethodsAn evaluative study using qualitative methods was conducted within a collaborative research approach involving different stakeholders, including the ministerial advisor and the four project managers responsible for supporting the implementation of the QAP, as well as researchers/scientific advisors. To support these organizations, we developed tailored, 2-page paper dashboards, detailing quantitative data on the prevalence of dementia, the use of health services by persons with dementia, and achievements and challenges of the QAP implementation in each organization’s jurisdiction. We then conducted 23 focus groups with the managers and leading clinicians involved in the implementation of the QAP of each regional health organization. Real-time notes were taken using a structured observation grid. Content analysis was conducted according to different regions (organizations with university mandates or nearby organizations, labeled “university/peripheral”; organizations for which only part of the territory is in rural areas, labeled “mixed”; and organizations in remote or isolated areas, labeled “remote/isolated”) and according to different types of participants (managers, leading clinicians, and other participants). ResultsParticipants from organizations in all regions expressed interest in these dashboards and found them useful in several ways. However, they highlighted the need for indicators on orphan patients and other health care providers. Differences between regions were observed, particularly in the interest in continuity of care in university/peripheral regions and the need for diagnostic tools adapted to the culture in remote/isolated regions. ConclusionsThese dashboards support the implementation of an Alzheimer Plan and contribute to the emergence of a learning health care system culture. This project allows each region to increase its monitoring capacity for the implementation of the QAP and facilitates reflection among individuals locally carrying out the implementation. The perspectives expressed will guide the preparation of the next iteration of the dashboards.