5α-reductase inhibitors with or without alpha-blockers and risk of incident upper tract urothelial carcinoma in men with benign prostatic hyperplasia: Analysis of US insurance claims data.

BACKGROUND: Increasing data suggests that androgen receptor signaling may play an important role in the carcinogenesis of urothelial cancers. While the chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results, the evidence regarding 5-ARi treatment, and the risk of incident Upper Tract Urothelial Carcinoma (UTUC) development is lacking. Therefore, our objective was to investigate the impact of the 5-ARi administration on the incidence of new UTUC cases using a large US database. METHODS: The MerativeTM Marketscan® database was used to identify men ≥ 50 years old with a diagnosis of BPH and an active 5-ARi prescription between 2007 and 2021 and were subsequently matched with paired controls. A multivariable Cox regression model was implemented to ascertain the association of 5-ARi and/or alpha-blocker (α-B) medications on the incidence of UTUC. Additional subgroup analyses were conducted based on exposure risk (with a 2-year threshold) to investigate the relationship between 5-ARi and UTUC over time. RESULTS: Overall, n=1,103,743 men BPH without prescriptions for BPH, n=31,142 men on 5-ARi, and n=160,049 using 5-ARi + α-B were identified. Over the follow-up period, a total of n=4,761 patients were diagnosed with UTUC. After matching, UTUC incidence ranged from 0.36% to 0.41% in men without active BPH therapy vs. 0.30% and 0.52% for the 5-ARi and 5-ARi + α-B groups, respectively. In multivariable analysis, the chemoprotective effect on UTUC risk was not observed for either 5-ARi monotherapy (adjusted hazard ratio [aHR]: 0.91, 95% CI: 0.58-1.44) or 5-ARi + α-B combination (aHR: 1.02, 95% CI: 0.87-1.19). This remained true for both short-term (≤ 2 years) and long-term (> 2 years) follow-up periods. CONCLUSIONS: The use of 5-ARi for BPH, whether used alone or in combination with α-B, is not associated with incident UTUC.

Elucidating the sustainability of 700 y of Inuvialuit beluga whale hunting in the Mackenzie River Delta, Northwest Territories, Canada.

Beluga whales play a critical role in the subsistence economies and cultural heritage of Indigenous communities across the Arctic, yet the effects of Indigenous hunting on beluga whales remain unknown. Here, we integrate paleogenomics, genetic simulations, and stable δ13C and δ15N isotope analysis to investigate 700 y of beluga subsistence hunting in the Mackenzie Delta area of northwestern Canada. Genetic identification of the zooarchaeological remains, which is based on radiocarbon dating, span three time periods (1290 to 1440 CE; 1450 to 1650 CE; 1800 to 1870 CE), indicates shifts across time in the sex ratio of the harvested belugas. The equal number of females and males harvested in 1450 to 1650 CE versus more males harvested in the two other time periods may reflect changes in hunting practices or temporal shifts in beluga availability. We find temporal shifts and sex-based differences in δ13C of the harvested belugas across time, suggesting historical adaptability in the foraging ecology of the whales. We uncovered distinct mitochondrial diversity unique to the Mackenzie Delta belugas, but found no changes in nuclear genomic diversity nor any substructuring across time. Our findings indicate the genomic stability and continuity of the Mackenzie Delta beluga population across the 700 y surveyed, indicating the impact of Inuvialuit subsistence harvests on the genetic diversity of contemporary beluga individuals has been negligible.

How do microtine rodent abundance, snow and landscape parameters influence pine marten Martes martes population dynamics?

The pine marten (Martes martes) occupies the northernmost extent of its distribution in Norway, where microtine rodents are an important food item. The relationship between microtine rodent abundance and pine marten population dynamics is not well understood. In this paper, we examined this relationship and tested if environmental factors (e.g. snow depth, elevation, mature spruce forest density and agricultural land density) modulate pine marten population dynamics. We calculated pine marten abundance indices using data collected from 593 unique snow transects surveyed between 2003 and 2014 in Hedmark, Norway. We employed a Partial Rate Correlation Function to identify potential cyclicity in pine marten populations. We did not observe any cyclical patterns in pine marten populations within our short time series. Instead, their population appeared to be directly density-dependent. Although the population growth rate of pine marten tended to increase with increasing elevation, it was not affected by individual variables including a microtine rodent abundance index and snow depth. However, the annual growth rate of pine marten populations was positively affected by the interaction between the microtine rodent abundance index and increasing elevation. Pine marten abundance increased with microtine rodent abundance, elevation, snow depth and density of mature spruce forest, but decreased with increasing agricultural land density. Pine martens are opportunistic diet generalists that can switch between prey and cache food for later consumption. They are also strongly territorial with delayed implantation and are slow to respond to environmental changes due to their relatively low reproductive potential. These life-history traits may mitigate the effects of fluctuating microtine rodent abundance on pine marten reproduction and survival. Nevertheless, our findings suggest that microtine rodents still serve as important prey which can influence the population dynamics of pine martens in higher elevation habitats where alternative prey may be less available.

Assessing Artificial Intelligence-Generated Responses to Urology Patient In-Basket Messages.

INTRODUCTION: Electronic patient messaging utilization has increased in recent years and has been associated with physician burnout. ChatGPT is a language model that has shown the ability to generate near-human level text responses. This study evaluated the quality of ChatGPT responses to real-world urology patient messages. METHODS: One hundred electronic patient messages were collected from a practicing urologist's inbox and categorized based on the question content. Individual responses were generated by entering each message into ChatGPT. The questions and responses were independently evaluated by 5 urologists and graded on a 5-point Likert scale. Questions were graded based on difficulty, and responses were graded based on accuracy, completeness, harmfulness, helpfulness, and intelligibleness. Whether or not the response could be sent to a patient was also assessed. RESULTS: Overall, 47% of responses were deemed acceptable to send to patients. ChatGPT performed better on easy questions with 56% of responses to easy questions being acceptable to send as compared to 34% of difficult questions (P = .03). Responses to easy questions were more accurate, complete, helpful, and intelligible than responses to difficult questions. There was no difference in response quality based on question content. CONCLUSIONS: ChatGPT generated acceptable responses to nearly 50% of patient messages with better performance for easy questions compared to difficult questions. Use of ChatGPT to help respond to patient messages can help to decrease the time burden for the care team and improve wellness. Artificial intelligence performance will likely continue to improve with advances in generative artificial intelligence technology.

Sociodemographic Trends and Perinatal Outcomes in Fathers 50 Years and Older.

Importance: The age of fathers at childbirth is rising, with an increasing number of births attributed to older fathers. While the impact of advanced paternal age has been documented, sociodemographic data about fathers aged 50 years and older remain scarce. Objectives: To explore sociodemographic and temporal trends among the oldest US fathers (age ≥50 years) and their associations with perinatal outcomes. Design, Setting, and Participants: This retrospective cross-sectional study included data from all US births from 2011 to 2022 using the National Vital Statistics System. Data were analyzed from August 2023 and May 2024. Exposures: Reported paternal age at childbirth. Main Outcomes and Measures: Outcomes of interest were sociodemographic factors, temporal trends in older fatherhood, and perinatal outcomes, including preterm birth, low birth weight, gestational diabetes, gestational hypertension, assisted reproductive technology (ART), rates of maternal primiparity, and the infant sex ratio. Results: From 2011 to 2022, the US recorded 46 195 453 births, with an overall mean (SD) paternal age of 31.5 (6.8) years and 484 507 (1.1%) involving fathers aged 50 years or older, 47 785 (0.1%) aged 60 years or older, and 3777 (0.008%) aged 70 years or older. Births to fathers aged 50 years or older increased from 1.1% in 2011 to 1.3% in 2022 (P for trend < .001). Fathers aged 50 years or older were more diverse, with variations in educational achievement and race and ethnicity. Marital status and maternal racial and ethnic and educational backgrounds also varied by paternal age and race. Despite controlling for maternal age and other sociodemographic and perinatal factors, every 10-year increase in paternal age was consistently associated with greater use of ART (eg, age 50-59 years: adjusted odds ratio [aOR], 2.23; 95% CI, 2.19-2.27), higher likelihood of first maternal birth (eg, age 50-59 years: aOR, 1.16; 95% CI, 1.15-1.17), and increased risks of preterm birth (eg, age 50-59 years: aOR, 1.16; 95% CI, 1.15-1.18) and low birth weight (eg, age 50-59 years: aOR, 1.14; 95% CI, 1.13-1.15) compared with fathers aged 30 to 39 years. No significant changes in the infant sex ratio were observed, except among fathers aged 70 years or older (aOR, 0.92; 95% CI, 0.86-0.99) and 75 years or older (aOR, 0.84; 95% CI, 0.73-0.97), who showed a decreased likelihood of having male offspring. Conclusions and Relevance: In this cross-sectional study of all US births from 2011 to 2022, the percentage attributed to older fathers, while small, increased. Notable variations in paternal and maternal race and education were identified. Older fatherhood was associated with increased ART use, first-time maternal births, adverse perinatal outcomes, and altered sex ratio. Further research of this population is crucial for improving patient counseling and family planning.

One-factor sex determination evolves without linkage between feminizing and masculinizing mutations.

The evolution of separate sexes from cosexuality requires at least two mutations: a feminizing allele to cause female development and a masculinizing allele to cause male development. Classically, the double mutant is assumed to be sterile, which leads to two-factor sex determination where male and female sex chromosomes differ at two loci. However, several species appear to have one-factor sex determination where sexual development depends on variation at a single locus. We show that one-factor sex determination evolves when the double mutant develops as a male or a female. The feminizing allele fixes when the double mutant is male, and the masculinizing allele fixes when the double mutant is female. The other locus then gives XY or ZW sex determination based on dominance: for example, a dominant masculinizer becomes a Y chromosome. Although the resulting sex determination system differs, the conditions required for feminizers and masculinizers to spread are the same as in classical models, with the important difference that the two alleles do not need to be linked. Thus, we reveal alternative pathways for the evolution of sex determination and discuss how they can be distinguished using new data on the genetics of sex determination.

Service development project to pilot a digital technology innovation for video direct observation of therapy in adult patients with asthma.

BACKGROUND: Adherence to pharmacotherapy and use of the correct inhaler technique are important basic principles of asthma management. Video- or remote-direct observation of therapy (v-DOT) could be a feasible approach to facilitate monitoring and supervising therapy, supporting the delivery of standard care. OBJECTIVE: To explore the utility and the feasibility of v-DOT to monitor inhaler technique and adherence to treatment in adults attending the asthma outpatient service in a tertiary hospital in Northern Ireland. METHOD: The project evaluated use of the technology with 10 asthma patients. Patient and clinician feedback was obtained, in addition to measures of patient engagement and disease-specific clinical markers to assess the feasibility and utility of v-DOT technology in this group of patients. RESULTS: The engagement rate with v-DOT for participating patients averaged 78% (actual video uploads vs expected video uploads) over a median 7 week usage period. Although 50% of patients reported a technical issue at some stage during the usage period, all patients and clinicians reported that the technology was easy to use and that they were satisfied with the outcomes. A range of positive impacts were observed, including optimised inhaler technique and an observed improvement in lung function. An increase in asthma control test scores aligned with clinical aims to promote adherence and alleviate symptoms. CONCLUSION: The v-DOT technology was shown to be a feasible method of assessing inhaler technique and monitoring adherence in this small group of adult asthma patients. A range of positive impacts for participating patients and clinicians were observed. Not all patients invited to join the project agreed to participate or engage with using the technology, highlighting that in this setting, digital modes of delivering care provide only one of the approaches in the necessary "tool kit" for clinicians and patients.

Factors associated with dating app use for sexual "hookups" in the United States: insights from the National Survey of Family Growth.

BACKGROUND: The use of dating applications for matchmaking and sexual exploits ("hookups") has increased, and this modern phenomenon has supplanted traditional socialization and relationship formation. To date, sociodemographic data on the use of dating apps has been limited. AIM: In this study, we sought to identify predictors associated with the use of dating apps in the United States. METHODS: Using cross-sectional data from the 2017-2019 National Survey of Family Growth, we examined sociodemographic determinants influencing the use of dating apps to find partners for sexual intercourse. We constructed survey-weighted regression models to study these associations, with additional sensitivity analyses performed within specific subgroups. Furthermore, this study investigated the correlation of app use with sexual frequency. OUTCOME: Study outcomes were participant data regarding reported use of dating apps for sexual intercourse in the 2017-2019 National Survey of Family Growth. RESULTS: A total of 11,225 respondents were examined, representing a survey-weighted total of approximately 143,201, 286 Americans. Among them, 757 respondents (6.7%), equating to approximately 8, 818, 743 individuals, reported dating app use for sexual hookups. Regression analysis revealed that factors such as male sex, White race, previous sexual experience, substance/alcohol use, history of sexually transmitted infections, same-sex attraction, and bisexuality increased the likelihood of dating app usage. Conversely, reduced odds of dating app use were observed among Catholics, Protestants, married/widowed individuals, and older respondents. Stratified analyses across various demographics, including male and female individuals aged 20 to 40 years, heterosexual, and lesbian, gay, and bisexual respondents, generally supported these trends. Notably, dating app use did not correlate with increased sexual frequency (adjusted incidence rate ratio: 1.10; 95% CI: 0.96-1.26; P = .16). CLINICAL IMPLICATIONS: Dating app use is prevalent among male patients and White individuals and correlates with increased sexually transmitted infection risk, alcohol/illicit substance use, past sexual experience, and popularity within the lesbian, gay, and bisexual community, all important considerations for public health interventions. Dating app use, however, was not associated with increased sexual encounters. STRENGTHS AND LIMITATIONS: Strengths of our study were the utilization of a national survey of individuals of reproductive age in the United States and focus on a clearly defined outcome of dating app utilization for the purposes of sexual intercourse. Limitations include self-reported survey responses and insufficient detail on the types and duration of dating app platforms and their use. CONCLUSIONS: Many sociodemographic factors, including male sex, White race, history of STIs, substance and alcohol use, and same-sex and bisexual attraction, were linked with dating app use. However, there was no increase in sexual frequency associated with dating app utilization. Further research is essential for integrating these technologies into the relational and sexual dynamics of individuals.

Patients' UX Impact on Medication Adherence in Czech Pilot Study for Chronically Ill.

This article presents a comprehensive and multistage approach to the development of the user experience (UX) for an mHealth application targeting older adult patients with chronic diseases, specifically chronic heart failure and chronic obstructive pulmonary disease. The study adopts a mixed methods approach, incorporating both quantitative and qualitative components. The underlying hypothesis posits that baseline medicine adherence knowledge (measured by the MARS questionnaire), beliefs about medicines (measured by the BMQ questionnaire), and level of user experience (measured by the SUS and UEQ questionnaires) act as predictors of adherence change after a period of usage of the mHealth application. However, contrary to our expectations, the results did not demonstrate the anticipated relationship between the variables examined. Nevertheless, the qualitative component of the research revealed that patients, in general, expressed satisfaction with the application. It is important to note that the pilot testing phase revealed a notable prevalence of technical issues, which may have influenced participants' perception of the overall UX. These findings contribute to the understanding of UX development in the context of mHealth applications for older adults with chronic diseases and emphasise the importance of addressing technical challenges to enhance user satisfaction and engagement.

Cardiac Arrest During a Ferric Derisomaltose Infusion Followed by Complete Heart Block: A Case Report.

Introduction: Ferric derisomaltose is the newest available parenteral iron formulation. Studies have demonstrated a good safety profile with improved tolerability compared to alternative parenteral iron formulations. To date there have been no reported acute, life-threatening cardiac events associated with ferric derisomaltose. Case Report: An 86-year-old male who had previously tolerated routine iron infusions received a first dose of ferric derisomaltose at an outpatient infusion clinic. Six minutes into the infusion the patient became unresponsive with no palpable pulse. Return of spontaneous circulation was achieved after two minutes of chest compressions. Electrocardiogram showed complete heart block requiring transcutaneous pacing and vasopressor administration. The patient was transferred to the emergency department for stabilization and then admitted to the cardiac intensive care unit. During admission, the patient received a dual-chamber, permanent pacemaker without complication and was ultimately discharged. Conclusion: It may be reasonable to consider parenteral iron as a toxicological etiology for patients presenting with complete heart block temporally associated with parenteral iron administration, particularly in patients with underlying conduction abnormalities.

Locally adaptive inversions in structured populations.

Inversions have been proposed to facilitate local adaptation, by linking together locally coadapted alleles at different loci. Prior work addressing this question theoretically has considered the spread of inversions in "continent-island" scenarios in which there is a unidirectional flow of maladapted migrants into the island population. In this setting, inversions capturing locally adaptive haplotypes are most likely to invade when selection is weak, because stronger local selection (i) more effectively purges maladaptive alleles and (ii) generates linkage disequilibrium between adaptive alleles, thus lessening the advantage of inversions. We show this finding only holds under limited conditions by studying the establishment of inversions in a more general two-deme model, which explicitly considers the dynamics of allele frequencies in both populations linked by bidirectional migration. In this model, the level of symmetry between demes can be varied from complete asymmetry (continent-island) to complete symmetry. For symmetric selection and migration, strong selection increases the allele frequency divergence between demes thereby increasing the frequency of maladaptive alleles in migrants, favoring inversions-the opposite of the pattern seen in the asymmetric continent-island scenario. We also account for the likelihood that a new inversion captures an adaptive haplotype in the first instance. When considering the combined process of capture and invasion in "continent island" and symmetric scenarios, relatively strong selection increases inversion establishment probability. Migration must also be low enough that the inversion is likely to capture an adaptive allele combination, but not so low as to eliminate the inversion's advantage. Overall, our analysis suggests that inversions are likely to harbor larger effect alleles that experience relatively strong selection.

Dynamic measurement of airway surface liquid volume with an ex vivo trachea-chip.

The volume and composition of airway surface liquid (ASL) is regulated by liquid secretion and absorption across airway epithelia, controlling the pH, solute concentration, and biophysical properties of ASL in health and disease. Here, we developed a method integrating explanted tracheal tissue with a micro-machined device (referred to as "ex vivo trachea-chip") to study the dynamic properties of ASL volume regulation. The ex vivo trachea-chip allows real-time measurement of ASL transport (Jv) with intact airway anatomic structures, environmental control, high-resolution, and enhanced experimental throughput. Applying this technology to freshly excised tissue we observed ASL absorption under basal conditions. The apical application of amiloride, an inhibitor of airway epithelial sodium channels (ENaC), reduced airway liquid absorption. Furthermore, the basolateral addition of NPPB, a Cl- channel inhibitor, reduced the basal rate of ASL absorption, implicating a role for basolateral Cl- channels in ASL volume regulation. When tissues were treated with apical amiloride and basolateral methacholine, a cholinergic agonist that stimulates secretion from airway submucosal glands, the net airway surface liquid production shifted from absorption to secretion. This ex vivo trachea-chip provides a new tool to investigate ASL transport dynamics in pulmonary disease states and may aid the development of new therapies targeting ASL regulation.

Characterization of blue-green blood leukocyte inclusions and accompanying clinical, hematologic, and serum biochemical changes in dogs.

BACKGROUND: Lipofuscin-like cytoplasmic inclusions have been reported in human blood neutrophils and monocytes but have not been described in dogs. In people, these "green granules of death" have been associated with moderate to severe hepatocellular injury and high mortality. OBJECTIVES: To describe clinicopathologic abnormalities, diagnoses, and outcomes of dogs with greenish inclusions in blood neutrophils or monocytes, and to determine if the inclusions have features of lipofuscin. METHODS: Clinical cases were identified prospectively through routine evaluation of CBC samples. Leukocyte inclusions were characterized with routine staining and assessed for iron and autofluorescence. Additional cases were identified by examination of archived blood smears from dogs meeting search criteria for hepatocellular injury, and clinicopathologic findings were recorded. RESULTS: All 7 prospectively identified dogs with inclusions had inflammation and moderate to marked increases in serum alanine aminotransferase (ALT) activity, as did the 4 dogs identified from the 97 meeting retrospective search criteria. The inclusions were Prussian blue-negative (5/5) with broad-spectrum autofluorescence (5/5) and the appearance of lipofuscin with and without Wright staining. Most clinical diagnoses involved hepatic disorders (5/7 prospective and 3/4 retrospective cases) or pancreatitis (3/7 prospective and 2/4 retrospective cases), and some involved both; 8 of 11 dogs died within 7 days of admission. CONCLUSIONS: Blue-green cytoplasmic inclusions uncommonly found in blood neutrophils ± monocytes of routine canine blood smears have stained and unstained properties of lipofuscin and suggest the presence of hepatocellular injury, often severe. Reporting these inclusions is recommended to guide clinical management.

Evaluation of medication safety assessment tools for pharmacist-led medication reviews: the Eastern European pilot project.

Background: Pharmacist-led medication reviews (MR) are one of the key methods to support medication safety in polypharmacy patients. The aims of this study were to pilot MRs in Eastern European community pharmacies, describe medication use in polypharmacy patients, and evaluate the usability of medication safety assessment tools. Methods: The MR pilot was undertaken in Estonia, Latvia, Poland, Hungary, Romania, and Bulgaria. Patients who used at least five medicines were directed to the service by their GPs. Data on drug-related problems (DRPs) and adherence were collected by pharmacists through structured patient interviews. Databases for identification of potential drug-drug interactions (pDDIs) and adverse drug reactions (ADRs) named Inxbase/Riskbase, as well as an integrated tool comprising potentially inappropriate medicines (PIMs) lists EU(7)-PIM and EURO-FORTA, were applied retroactively to the MR pilot data to investigate possibilities for their use and to describe medication use and potential risks in the study population. Results: A total of 318 patients were included in the study, 250 of them elderly (≥65 years). One hundred and eighty (56.6%) participants had a total of 504 pDDIs based on Inxbase analysis. On average, there were 1.6 pDDIs per participant. Twenty-five (5.0%) of the 504 pDDIs were in a high-risk category. A total of 279 (87.7%) participants had a potential ADR in at least one of 10 Riskbase categories. One hundred and fifty-four (20.8%) of the potential ADRs were in a high-risk category. Twenty-seven pDDIs and 68 ADRs documented as DRPs during the service were not included in the databases. Using the integrated EU(7)-PIM/EURO-FORTA PIM list, a total of 816 PIMs were found in 240 (96%) of the 250 elderly participants (on average 3.4 PIMs per elderly participant). Seventy-one (29.6%) of the participants were using high-risk PIMs. Twenty-one percent of high-risk PIMs and 13.8% of medium-risk PIMs were documented as DRPs by the pharmacists during the pilot. Conclusion: Medication safety assessment tools can be useful in guiding decision-making during MRs; however, these tools cannot replace patient interviews and monitoring. Tools that include a thorough explanation of the potential risks and are easy to use are more beneficial for MRs.

Conduction System Pacing in Pediatrics and Congenital Heart Disease: A Case Report and Literature Review.

Conduction system pacing involving either His bundle pacing (HBP) or left bundle branch pacing (LBBP) is a modality that has been introduced as a safe and effective alternative to right ventricular (RV) pacing to help prevent pacemaker-associated cardiomyopathy. While HBP has been employed in the pediatric and congenital populations, several small studies have shown LBBP to be safe and effective in the pediatric population. We present a patient with congenital atrioventricular block and postoperative ventricular septal defect repair cardiomyopathy with subsequent left ventricular function improvement following a transition from an RV epicardial pacemaker system to an LBBP system. This case report serves as a foundation for a review of the current state of LBBP in pediatrics and congenital heart disease.

Multiyear Interval Changes in Aortic Wall Shear Stress in Patients with Bicuspid Aortic Valve Assessed by 4D Flow MRI.

BACKGROUND: In patients with bicuspid aortic valve (BAV), 4D flow MRI can quantify regions exposed to abnormal aortic hemodynamics, including high wall shear stress (WSS), a known stimulus for arterial wall dysfunction. However, the long-term multiscan reproducibility of 4D flow MRI-derived hemodynamic parameters is unknown. PURPOSE: To investigate the long-term stability of 4D flow MRI-derived peak velocity, WSS, and WSS-derived heatmaps in patients with BAV undergoing multiyear surveillance imaging. STUDY TYPE: Retrospective. POPULATION: 20 BAV patients (mean age 48.4 ± 13.9 years; 14 males) with five 4D flow MRI scans, with intervals of at least 6 months between scans, and 125 controls (mean age: 50.7 ± 15.8 years; 67 males). FIELD STRENGTH/SEQUENCE: 1.5 and 3.0T, prospectively ECG and respiratory navigator-gated aortic 4D flow MRI. ASSESSMENT: Automated AI-based 4D flow analysis pipelines were used for data preprocessing, aorta 3D segmentation, and quantification of ascending aorta (AAo) peak velocity, peak systolic WSS, and heatmap-derived relative area of elevated WSS compared to WSS ranges in age and sex-matched normative control populations. Growth rate was derived from the maximum AAo diameters measured on the first and fifth MRI scans. STATISTICAL TESTS: One-way repeated measures analysis of variance. P < 0.05 indicated significance. RESULTS: One hundred 4D flow MRI exams (five per patient) were analyzed. The mean total follow-up duration was 5.5 ± 1.1 years, and the average growth rate was 0.3 ± 0.2 mm/year. Peak velocity, peak systolic WSS, and relative area of elevated WSS did not change significantly over the follow-up period (P = 0.64, P = 0.69, and P = 0.35, respectively). The patterns and areas of elevated WSS demonstrated good reproducibility on semiquantitative assessment. CONCLUSION: 4D flow MRI-derived peak velocity, WSS, and WSS-derived heatmaps showed good multiyear and multiscan stability in BAV patients with low aortic growth rates. These findings underscore the reliability of these metrics in monitoring BAV patients for potential risk of dilation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Gametic selection favours polyandry and selfing.

Competition among pollen or sperm (gametic selection) can cause evolution. Mating systems shape the intensity of gametic selection by determining the competitors involved, which can in turn cause the mating system itself to evolve. We model the bidirectional relationship between gametic selection and mating systems, focusing on variation in female mating frequency (monandry-polyandry) and self-fertilisation (selfing-outcrossing). First, we find that monandry and selfing both reduce the efficiency of gametic selection in removing deleterious alleles. This means that selfing can increase mutation load, in contrast to cases without gametic selection where selfing purges deleterious mutations and decreases mutation load. Second, we explore how mating systems evolve via their effect on gametic selection. By manipulating gametic selection, polyandry can evolve to increase the fitness of the offspring produced. However, this indirect advantage of post-copulatory sexual selection is weak and is likely to be overwhelmed by any direct fitness effects of mating systems. Nevertheless, gametic selection can be potentially decisive for selfing evolution because it significantly reduces inbreeding depression, which favours selfing. Thus, the presence of gametic selection could be a key factor driving selfing evolution.

The paternal role in pregnancy loss.

In this comprehensive review, the intricate relationship between paternal factors and pregnancy loss is examined. While pregnancy loss has historically been predominantly attributed to maternal factors, recent research underscores the significant contribution of the male partner. The review delves into various aspects of paternal influence, including paternal age, health, chromosome abnormalities, Y chromosome deletions, and sperm DNA fragmentation. Notably, advanced paternal age is found to be associated with an increased risk of recurrent pregnancy loss, shedding light on the importance of understanding the impact of aging on male fertility. Additionally, paternal health, particularly metabolic syndrome, emerges as a noteworthy factor contributing to pregnancy loss. Chromosome abnormalities in male partners, such as balanced translocations, and Y chromosome microdeletions are explored in the context of pregnancy loss risk. Moreover, the review highlights the growing body of evidence linking sperm DNA fragmentation and sperm protein abnormalities to spontaneous pregnancy loss, emphasizing the significance of sperm health in reproductive outcomes. Overall, this review provides a comprehensive overview of the multifaceted role of the male partner in pregnancy loss, calling for a more inclusive approach to pregnancy loss investigations that encompasses both maternal and paternal factors.

Autologous bone marrow mononuclear cells to treat severe traumatic brain injury in children.

Autologous bone marrow mononuclear cells (BMMNCs) infused after severe traumatic brain injury have shown promise for treating the injury. We evaluated their impact in children, particularly their hypothesized ability to preserve the blood-brain barrier and diminish neuroinflammation, leading to structural CNS preservation with improved outcomes. We performed a randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial at two children's hospitals in Houston, TX and Phoenix, AZ, USA (NCT01851083). Patients 5-17 years of age with severe traumatic brain injury (Glasgow Coma Scale score ≤ 8) were randomized to BMMNC or placebo (3:2). Bone marrow harvest, cell isolation and infusion were completed by 48 h post-injury. A Bayesian continuous reassessment method was used with cohorts of size 3 in the BMMNC group to choose the safest between two doses. Primary end points were quantitative brain volumes using MRI and microstructural integrity of the corpus callosum (diffusivity and oedema measurements) at 6 months and 12 months. Long-term functional outcomes and ventilator days, intracranial pressure monitoring days, intensive care unit days and therapeutic intensity measures were compared between groups. Forty-seven patients were randomized, with 37 completing 1-year follow-up (23 BMMNC, 14 placebo). BMMNC treatment was associated with an almost 3-day (23%) reduction in ventilator days, 1-day (16%) reduction in intracranial pressure monitoring days and 3-day (14%) reduction in intensive care unit (ICU) days. White matter volume at 1 year in the BMMNC group was significantly preserved compared to placebo [decrease of 19 891 versus 40 491, respectively; mean difference of -20 600, 95% confidence interval (CI): -35 868 to -5332; P = 0.01], and the number of corpus callosum streamlines was reduced more in placebo than BMMNC, supporting evidence of preserved corpus callosum connectivity in the treated groups (-431 streamlines placebo versus -37 streamlines BMMNC; mean difference of -394, 95% CI: -803 to 15; P = 0.055), but this did not reach statistical significance due to high variability. We conclude that autologous BMMNC infusion in children within 48 h after severe traumatic brain injury is safe and feasible. Our data show that BMMNC infusion led to: (i) shorter intensive care duration and decreased ICU intensity; (ii) white matter structural preservation; and (iii) enhanced corpus callosum connectivity and improved microstructural metrics.