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While direct oral anticoagulants (DOACs) are frequently used to treat venous thromboembolism (VTE), the outcomes of patients with inherited thrombophilia (IT) receiving DOACs for VTE remain understudied. We used data from the international RIETE registry to compare the rates of VTE recurrences, major bleeding, and mortality during anticoagulant treatment in VTE patients with and without IT, grouped by the use of DOACs or standard anticoagulant therapy. Among 103,818 enrolled patients, 21,089 (20.3%) were tested for IT, of whom 8422 (39.9%) tested positive: Protein C deficiency 294, Protein S deficiency 726, Antithrombin deficiency 240, Factor V Leiden 2248, Prothrombin gene mutation 1434, combined IT 3480. Overall, 14,189 RIETE patients (6.2% with IT) received DOACs, and 89,629 standard anticoagulation (8.4% with IT), mostly with heparins followed by vitamin K antagonists. Proportions of patients receiving DOACs did not differ between IT-positive and IT-negative patients. Rates of VTE recurrence on anticoagulant treatment were highest in patients with AT deficiency (P < 0.01). Rates of on-treatment major bleeding and all-cause mortality were lowest among patients with Factor V Leiden (FVL) or PT G20210A mutations, compared with patients who tested negative. Patients with IT who received DOACs had lower rates of major bleeding than those receiving standard anticoagulation. Excluding FVL and Protein S deficiency, patients with IT had lower rates of VTE recurrence with DOACs than with standard anticoagulation. DOACs are equally safe and effective in VTE patients with IT, with lower bleeding rates than those on standard anticoagulation. [ABSTRACT FROM AUTHOR]

This study proposes a methodology for developing deterioration models and predicting the service lives of vertical assets of urban water systems (i.e., water storage tanks and pumping stations) using regression analysis. The main factors contributing to the deterioration of these assets are analyzed. Simple and multiple linear regression models of average and maximum deterioration are calculated for 22 water storage tanks and 17 wastewater pumping stations. Data on a set of four water storage tanks are used to validate the developed deterioration models. Service life prediction is carried out using the developed models and considering two maximum deterioration levels: the maximum recommended and admissible deterioration levels. Two water storage tanks are further studied to illustrate and discuss the effect of maintenance and rehabilitation interventions on asset service life by comparing the asset deterioration before and after the interventions. Results include simple linear regression models of average and maximum deterioration indices as a function of asset age and multiple linear regression models that incorporate other physical, operational and environmental factors. The results show that simple linear regression models of asset deterioration show a better predictive power than multiple regression models. Despite the higher data variability of multiple regression models, these models allow to include the random process of asset deterioration, through the calculation of the standard deviation. This study also shows that periodic interventions are a preferable maintenance and rehabilitation strategy over major sporadic rehabilitation interventions since it allows to maintain assets in good condition and to extend their service life almost indefinitely. Plain Language Summary: Urban water assets are continuously deteriorating and more investments are necessary to maintain adequate levels of service. However, investment budgets are often limited and appropriate deterioration models and reliably predicted service lives are essential for planning and scheduling maintenance actions. This paper develops deterioration models for water storage tanks and wastewater pumping stations based on the identification and classification of anomalies through visual inspection. Additionally, service lives (i.e., the period from the installation until the asset or its components fulfill the service requirements) were obtained and compared with reference values. Finally, the effect of maintenance actions and rehabilitation interventions on the service life of vertical assets was discussed. In order to maintain a good asset condition and extend its service life quasi‐indefinitely, periodic and well‐established interventions are a preferable maintenance and rehabilitation strategy over major sporadic rehabilitation interventions. Key Points: Physical, operational and environmental factors of asset deterioration are discussed and deterioration models are summarizedPredicted service lives are obtained and the effect of maintenance and rehabilitation interventions on asset service life are analyzedThe methodology for service life prediction can be applied to other water assets [ABSTRACT FROM AUTHOR]

Background: Age is a major risk factor for venous thromboembolism (VTE), yet patients aged ≥90 years are under‐represented in clinical trials of anticoagulant therapy. The objectives were to describe and compare patient clinical characteristics, treatments, and outcomes (VTE recurrence, bleeding, and mortality) during the first 3 months of anticoagulation between VTE patients aged ≥90 years and those aged <90 years. Methods: We analyzed data from the Registro Informatizado Enfermedad TromboEmbὀlica (RIETE), an ongoing global observational registry of patients with objectively confirmed acute VTE. Results: From January 2001 to October 2022, 96,701 patients were registered in RIETE, of whom 3262 (3.4%) were aged ≥90 years. Patients aged ≥90 years were less likely to be men, and to have experienced cancer or recent surgery, but more likely to manifest immobility, chronic heart failure, anemia, renal insufficiency, or dementia than those aged <90 years. Most (99.6%) patients aged ≥90 years were receiving anticoagulant therapy. During the first 3 months, 26 patients aged ≥90 years developed VTE recurrences, 116 experienced major bleeding, and 564 died. Among patients initially presenting with pulmonary embolism (PE), deaths due to PE exceeded those due to fatal bleeding (76 vs. 19). Among those initially presenting with isolated deep‐vein thrombosis (DVT), it was the reverse (2 vs. 11 deaths). Conclusions: In patients aged ≥90 years, the difference in the outcome of anticoagulant treatment depending on the initial presentation of VTE could suggest a need for different management approaches. Clinical trials evaluating the optimal duration of anticoagulation according to initial VTE presentation are warranted to limit excess deaths in this particular population. [ABSTRACT FROM AUTHOR]

Background: In COPD, the bronchial epithelium shows a pathologically activated Wnt pathway. Sclerostin (SOST) is a secreted glycoprotein that is associated with bone metabolism and blocks the Wnt pathway. We hypothesized that low sclerostin levels might be associated with lung function and COPD exacerbations in patients., Methods: We studied 139 outpatients with stable COPD and normal kidney function. We assessed the serum levels of SOST and bone metabolism parameters, body composition, clinical characteristics and lung function at baseline. We followed the patients prospectively for 12 months after enrolment. Moderate exacerbations and hospital admissions were recorded during follow-up., Results: The serum SOST levels were 23.98±7.6 pmol/l (men: 25.5±7.7 pmol/l, women: 20.3±5.9 pmol/l (p < 0.001)). SOST showed correlations with age (r = 0.36), FFMI (r = 0.38), FEV1 (r = 0.27), DLCO (r = 0.39), 6MWD (r = 0.19) and CAT (r = -0.24). In multivariate linear regression analysis, only age (beta=0.264) and FFMI (beta=1.241) remained significant. SOST showed a significant negative correlation with serum phosphorus (r = -0.29). Cox proportional risk analysis indicated that patients in the lower tertile of SOST levels were at higher risk of moderate COPD exacerbation (HR 2.015, CI95% 1.136-3.577, p = 0.017) and hospital admission due to COPD (HR 5.142, CI95% 1.380-19.158, p = 0.015) than the rest of the patients., Conclusions: SOST levels are associated with body composition and lung function in patients with COPD. Furthermore, lower SOST levels predict a higher risk of exacerbations and hospitalization., Competing Interests: Declaration of interests None., (Copyright © 2022 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

The use of plant genetic resources (PGR)-wild relatives, landraces, and isolated breeding gene pools-has had substantial impacts on wheat breeding for resistance to biotic and abiotic stresses, while increasing nutritional value, end-use quality, and grain yield. In the Global South, post-Green Revolution genetic yield gains are generally achieved with minimal additional inputs. As a result, production has increased, and millions of hectares of natural ecosystems have been spared. Without PGR-derived disease resistance, fungicide use would have easily doubled, massively increasing selection pressure for fungicide resistance. It is estimated that in wheat, a billion liters of fungicide application have been avoided just since 2000. This review presents examples of successful use of PGR including the relentless battle against wheat rust epidemics/pandemics, defending against diseases that jump species barriers like blast, biofortification giving nutrient-dense varieties and the use of novel genetic variation for improving polygenic traits like climate resilience. Crop breeding genepools urgently need to be diversified to increase yields across a range of environments (>200 Mha globally), under less predictable weather and biotic stress pressure, while increasing input use efficiency. Given that the ~0.8 m PGR in wheat collections worldwide are relatively untapped and massive impacts of the tiny fraction studied, larger scale screenings and introgression promise solutions to emerging challenges, facilitated by advanced phenomic and genomic tools. The first translocations in wheat to modify rhizosphere microbiome interaction (reducing biological nitrification, reducing greenhouse gases, and increasing nitrogen use efficiency) is a landmark proof of concept. Phenomics and next-generation sequencing have already elucidated exotic haplotypes associated with biotic and complex abiotic traits now mainstreamed in breeding. Big data from decades of global yield trials can elucidate the benefits of PGR across environments. This kind of impact cannot be achieved without widescale sharing of germplasm and other breeding technologies through networks and public-private partnerships in a pre-competitive space., (© 2024 The Author(s). Global Change Biology published by John Wiley & Sons Ltd.)

Background: The clinical relevance of recurrent venous thromboembolism (VTE) after discontinuing anticoagulation in patients with COVID-19-associated VTE remains uncertain. We estimated the incidence rates and mortality of VTE recurrences developing after discontinuing anticoagulation in patients with COVID-19-associated VTE., Methods: A prospective, multicenter, non-interventional study was conducted between March 25, 2020, and July 26, 2023, including patients who had discontinued anticoagulation after at least 3 months of therapy. All patients from the registry were analyzed during the study period to verify inclusion criteria. Patients with superficial vein thrombosis, those who did not receive at least 3 months of anticoagulant therapy, and those who were followed for less than 15 days after discontinuing anticoagulation were excluded. Outcomes were: 1) Incidence rates of symptomatic VTE recurrences, and 2) fatal PE. The rate of VTE recurrences was defined as the number of patients with recurrent VTE divided by the patient-years at risk of recurrent VTE during the period when anticoagulation was discontinued., Findings: Among 1106 patients with COVID-19-associated VTE (age 62.3 ± 14.4 years; 62.9% male) followed-up for 12.5 months (p25-75, 6.3-20.1) after discontinuing anticoagulation, there were 38 VTE recurrences (3.5%, 95% confidence interval [CI]: 2.5-4.7%), with a rate of 3.1 per 100 patient-years (95% CI: 2.2-4.2). No patient died of recurrent PE (0%, 95% CI: 0-7.6%). Subgroup analyses showed that patients with diagnosis in 2021-2022 (vs. 2020) (Hazard ratio [HR] 2.86; 95% CI 1.45-5.68) or those with isolated deep vein thrombosis (vs. pulmonary embolism) (HR 2.31; 95% CI 1.19-4.49) had significantly higher rates of VTE recurrences., Interpretation: In patients with COVID-19-associated VTE who discontinued anticoagulation after at least 3 months of treatment, the incidence rate of recurrent VTE and the case-fatality rate was low. Therefore, it conceivable that long-term anticoagulation may not be required for many patients with COVID-19-associated VTE, although further research is needed to confirm these findings., Funding: Sanofi and Rovi, Sanofi Spain., Competing Interests: BB is supported by a Career Development Award from the American Heart Association and VIVA Physicians (#938814). BB was supported by the Scott Schoen and Nancy Adams IGNITE Award and is supported by the Mary Ann Tynan Research Scientist award from the Mary Horrigan Connors Center for Women's Health and Gender Biology at Brigham and Women's Hospital, and the Heart and Vascular Center Junior Faculty Award from Brigham and Women's Hospital. BB reports that he is a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of IVC filters. BB has not been involved in the litigation in 2022 or 2023 nor has he received any compensation in 2022 or 2023. BB reports that he is a member of the Medical Advisory Board for the North American Thrombosis Forum and serves in the Data Safety and Monitory Board of the NAIL-IT trial funded by the National Heart, Lung, and Blood Institute, and Translational Sciences. MM received fees from Sanofi, Leo Pharma, Rovi and the Catholic University of Murcia (Spain) sponsored the RIETE registry with unrestricted educational grants. Payments were made to the FUENTE foundation. DJ received honoraria for lectures from BMS and Sanofi. LJP received grants from Leo Pharma and MSD and personal fees from Daichii, Rovi, GlaxoSmithKline, BMS and Johnson and Johnson outside the submitted work. No other conflict of interest declared., (© 2024 The Authors.)

Common wheat (Triticum aestivum L.) is a major staple food crop, providing a fifth of food calories and proteins to the world's human population. Despite the impressive growth in global wheat production in recent decades, further increases in grain yield are required to meet future demands. Here we estimated genetic gain and genotype stability for grain yield (GY) and determined the trait associations that contributed uniquely or in combination to increased GY, through a retrospective analysis of top-performing genotypes selected from the elite spring wheat yield trial (ESWYT) evaluated internationally during a 14-year period (2003 to 2016). Fifty-six ESWYT genotypes and four checks were sown under optimally irrigated conditions in three phenotyping trials during three consecutive growing seasons (2018-2019 to 2020-2021) at Norman E. Borlaug Research Station, Ciudad Obregon, Mexico. The mean GY rose from 6.75 (24th ESWYT) to 7.87 t ha -1 (37th ESWYT), representing a cumulative increase of 1.12 t ha -1 . The annual genetic gain for GY was estimated at 0.96% (65 kg ha -1  year -1 ) accompanied by a positive trend in genotype stability over time. The GY progress was mainly associated with increases in biomass (BM), grain filling rate (GFR), total radiation use efficiency (RUE&#95;total), grain weight per spike (GWS), and reduction in days to heading (DTH), which together explained 95.5% of the GY variation. Regression lines over the years showed significant increases of 0.015 kg m -2  year -1 (p < 0.01), 0.074 g m -2  year -1 (p < 0.05), and 0.017 g MJ -1  year -1 (p < 0.001) for BM, GFR, and RUE&#95;total, respectively. Grain weight per spike exhibited a positive but no significant trend (0.014 g year -1 , p = 0.07), whereas a negative tendency for DTH was observed (- 0.43 days year -1 , p < 0.001). Analysis of the top ten highest-yielding genotypes revealed differential GY-associated trait contributions, demonstrating that improved GY can be attained through different mechanisms and indicating that no single trait criterion is adopted by CIMMYT breeders for developing new superior lines. We conclude that CIMMYT's Bread Wheat Breeding Program has continued to deliver adapted and more productive wheat genotypes to National partners worldwide, mainly driven by enhancing RUE&#95;total and GFR and that future yield increases could be achieved by intercrossing genetically diverse top performer genotypes., (© 2024. The Author(s).)

Wheat (Triticum aestivum L.) as a staple crop is closely interwoven into the development of modern society. Its influence on culture and economic development is global. Recent instability in wheat markets has demonstrated its importance in guaranteeing food security across national borders. Climate change threatens food security as it interacts with a multitude of factors impacting wheat production. The challenge needs to be addressed with a multidisciplinary perspective delivered across research, private, and government sectors. Many experimental studies have identified the major biotic and abiotic stresses impacting wheat production, but fewer have addressed the combinations of stresses that occur simultaneously or sequentially during the wheat growth cycle. Here, we argue that biotic and abiotic stress interactions, and the genetics and genomics underlying them, have been insufficiently addressed by the crop science community. We propose this as a reason for the limited transfer of practical and feasible climate adaptation knowledge from research projects into routine farming practice. To address this gap, we propose that novel methodology integration can align large volumes of data available from crop breeding programs with increasingly cheaper omics tools to predict wheat performance under different climate change scenarios. Underlying this is our proposal that breeders design and deliver future wheat ideotypes based on new or enhanced understanding of the genetic and physiological processes that are triggered when wheat is subjected to combinations of stresses. By defining this to a trait and/or genetic level, new insights can be made for yield improvement under future climate conditions., (© 2023 The Authors. The Plant Genome published by Wiley Periodicals LLC on behalf of Crop Science Society of America.)

Introduction: The burden related to smoking exposure is growing in many low-income settings. We aimed to quantify the use of smoked and smokeless tobacco in Mozambique in 2014/2015, and to compare the estimates with those obtained in 2005., Methods: A cross sectional study was conducted in 2014/2015 on a representative sample of the Mozambican population aged 15 to 64 years, following the World Health Organization Stepwise Approach to Chronic Disease Risk Factor Surveillance (STEPS). Prevalence estimates with 95% confidence intervals were computed for different categories of tobacco consumption. The age-standardised prevalence in the age-group 25-64 years was compared with results from a STEPS survey conducted in 2005., Results: Between 2005 and 2014/2015, the prevalence of daily smoking decreased from 9.1% to 3.4% (p < 0.05) in women and from 33.6% to 27.3% (p < 0.05) in men. There was a significant decrease in the daily consumption of hand-rolled cigarettes among women (from 3.1% to 1.4%, p < 0.05). Among men, there was a decrease in the prevalence of daily consumption of smokeless tobacco (from 3.5% to 1.0%, p < 0.05). In 2014/2015, both manufactured and hand-rolled cigarette consumption were more prevalent among men, while the use of smokeless tobacco was more common among women; the consumption of both hand-rolled cigarettes and smokeless tobacco were more prevalent in rural settings., Discussion and Conclusions: In Mozambique, there was a decrease in the prevalence of daily smokers in both genders and of daily consumption of smokeless tobacco among men between 2005 and 2014/2015. Efforts are needed to maintain the positive trends., (© 2023 Australasian Professional Society on Alcohol and other Drugs.)