Factor analysis of the Chinese version of the Autism Spectrum Quotient 10 and its association with schizotypal traits in adolescents and young adults in Hong Kong.

BACKGROUND: There is evidence suggesting that autistic traits are associated with schizotypal traits. This study examined the factor structure of the Autism Spectrum Quotient 10 (AQ-10) and its associations with schizotypal traits (measured by the Schizotypal Personality Questionnaire-Brief [SPQ-B]) in a cohort of Chinese adolescents and young adults. METHODS: Invitation letters, stratified by locations and housing types, were randomly sent to individuals aged 15 to 24 years for participation. Assessments were made using face-to-face or online interviews. Autistic traits were assessed using the Chinese version of the AQ-10. Schizotypal personality traits were assessed using the Chinese version of the 22-item SPQ-B. RESULTS: In total, 395 male and 536 female participants (mean age, 19.93 years) were recruited between July 2020 and May 2021. Exploratory factor analysis of the AQ-10 yielded three factors (theory of mind, task switching, and attention deficits) explaining 55.11% of the total variance. Autistic traits were positively correlated with schizotypal traits of disorganised features (r = 0.21, p < 0.001), interpersonal relationship deficits (r = 0.19, p < 0.001), and cognitive-perceptual deficits (r = 0.11, p = 0.001). CONCLUSION: In Chinese adolescents and young adults, autistic traits, especially task switching and attention deficits (compared with theory of mind) are more closely correlated with schizotypal personality traits. Disentangling the overlapping and diametrical structure of autistic traits and schizotypal traits may help understand their aetiologies, assessment, and interventions.

Temporal changes in the morphological and microbial diversity of biofilms on the surface of a submerged stone in the Danube River.

Epilithic biofilms are ubiquitous in large river environments and are crucial for biogeochemical processes, but their community structures and functions remain poorly understood. In this paper, the seasonal succession in the morphological structure and the taxonomic composition of an epilithic bacterial biofilm community at a polluted site of the Danube River were followed using electron microscopy, high-throughput 16S rRNA gene amplicon sequencing and multiplex/taxon-specific PCRs. The biofilm samples were collected from the same submerged stone and carried out bimonthly in the littoral zone of the Danube River, downstream of a large urban area. Scanning electron microscopy showed that the biofilm was composed of diatoms and a variety of bacteria with different morphologies. Based on amplicon sequencing, the bacterial communities were dominated by the phyla Pseudomonadota and Bacteroidota, while the most abundant archaea belonged to the phyla Nitrososphaerota and Nanoarchaeota. The changing environmental factors had an effect on the composition of the epilithic microbial community. Critical levels of faecal pollution in the water were associated with increased relative abundance of Sphaerotilus, a typical indicator of "sewage fungus", but the composition and diversity of the epilithic biofilms were also influenced by several other environmental factors such as temperature, water discharge and total suspended solids (TSS). The specific PCRs showed opportunistic pathogenic bacteria (e.g. Pseudomonas spp., Legionella spp., P. aeruginosa, L. pneumophila, Stenotrophomonas maltophilia) in some biofilm samples, but extended spectrum ß-lactamase (ESBL) genes and macrolide resistance genes could not be detected.

Effectiveness of immune checkpoint inhibitor therapy on bone metastases in non-small-cell lung cancer.

Background: Bone metastases (BoMs) are prevalent in patients with metastatic non-small-cell lung cancer (NSCLC) however, there are limited data detailing how BoMs respond to immune checkpoint inhibitors (ICIs). The purpose of this study was to compare the imaging response to ICIs of BoMs against visceral metastases and to evaluate the effect of BoMs on survival. Materials and methods: A retrospective, multicentre cohort study was conducted in patients with NSCLC treated with nivolumab or pembrolizumab in Alberta, Canada from 2015 to 2020. The primary endpoint was the real-world organ specific progression free survival (osPFS) of bone versus visceral metastases. Visceral metastases were categorized as adrenal, brain, liver, lung, lymph node, or other intra-abdominal lesions. The secondary outcome was overall survival (OS) amongst patients with and without BoMs. Results: A total of 573 patients were included of which all patients had visceral metastases and 243 patients (42.4%) had BoMs. High PD-L1 expression was identified in 268 patients (46.8%). No significant difference in osPFS was observed between bone, liver, and intra-abdominal metastases (p=0.20 and p=0.76, respectively), with all showing shorter osPFS than other disease sites. There was no difference in the osPFS of extra-thoracic sites of disease in patients with high PD-L1 expression. There was significant discordance between visceral disease response and bone disease response to ICI (p=0.047). The presence of BoMs was an independent poor prognostic factor for OS (HR 1.26, 95%CI: 1.05-1.53, p=0.01). Conclusion: Metastatic bone, liver, and intra-abdominal lesions demonstrated inferior clinical responses to ICI relative to other sites of disease. Additionally, the presence of bone and liver metastases were independent poor prognostic factors for overall survival. This real-world data suggests that BoMs respond poorly to ICI and may require treatment adjuncts for disease control.

Assessing the impact of inland navigation on the faecal pollution status of large rivers: A novel integrated field approach.

The contribution of ships to the microbial faecal pollution status of water bodies is largely unknown but frequently of human health concern. No methodology for a comprehensive and target-orientated system analysis was available so far. We developed a novel approach for integrated and multistage impact evaluation. The approach includes, i) theoretical faecal pollution source profiling (PSP, i.e., size and pollution capacity estimation from municipal vs. ship sewage disposal) for impact scenario estimation and hypothesis generation, ii) high-resolution field assessment of faecal pollution levels and chemo-physical water quality at the selected river reaches, using standardized faecal indicators (cultivation-based) and genetic microbial source tracking markers (qPCR-based), and iii) integrated statistical analyses of the observed faecal pollution and the number of ships assessed by satellite-based automated ship tracking (i.e., automated identification system, AIS) at local and regional scales. The new approach was realised at a 230 km long Danube River reach in Austria, enabling detailed understanding of the complex pollution characteristics (i.e., longitudinal/cross-sectional river and upstream/downstream docking area analysis). Faecal impact of navigation was demonstrated to be remarkably low at regional and local scale (despite a high local contamination capacity), indicating predominantly correct disposal practices during the investigated period. Nonetheless, faecal emissions were sensitively traceable, attributable to the ship category (discriminated types: cruise, passenger and freight ships) and individual vessels (docking time analysis) at one docking area by the link with AIS data. The new innovative and sensitive approach is transferrable to any water body worldwide with available ship-tracking data, supporting target-orientated monitoring and evidence-based management practices.

High-throughput quantification of quasistatic, dynamic and spall strength of materials across 10 orders of strain rates.

The response of metals and their microstructures under extreme dynamic conditions can be markedly different from that under quasistatic conditions. Traditionally, high strain rates and shock stresses are achieved using cumbersome and expensive methods such as the Kolsky bar or large spall experiments. These methods are low throughput and do not facilitate high-fidelity microstructure-property linkages. In this work, we combine two powerful small-scale testing methods, custom nanoindentation, and laser-driven microflyer (LDMF) shock, to measure the dynamic and spall strength of metals. The nanoindentation system is configured to test samples from quasistatic to dynamic strain-rate regimes. The LDMF shock system can test samples through impact loading, triggering spall failure. The model material used for testing is magnesium alloys, which are lightweight, possess high-specific strengths, and have historically been challenging to design and strengthen due to their mechanical anisotropy. We adopt two distinct microstructures, solutionized (no precipitates) and peak-aged (with precipitates) to demonstrate interesting upticks in strain-rate sensitivity and evolution of dynamic strength. At high shock-loading rates, we unravel an interesting paradigm where the spall strength vs. strain rate of these materials converges, but the failure mechanisms are markedly different. Peak aging, considered to be a standard method to strengthen metallic alloys, causes catastrophic failure, faring much worse than solutionized alloys. Our high-throughput testing framework not only quantifies strength but also teases out unexplored failure mechanisms at extreme strain rates, providing valuable insights for the rapid design and improvement of materials for extreme environments.

Long-term mortality after isolated coronary artery bypass grafting and risk factors for mortality.

BACKGROUND: Patients requiring coronary artery bypass grafting (CABG) have multiple co-morbidities which need to be considered in totality when determining surgical risks. The objective of this study is to evaluate short-term and long-term mortality rates of CABG surgery, as well as to identify the most significant risk factors for mortality after isolated CABG. METHODS: All patients with complete dataset who underwent isolated CABG between January 2008 and December 2017 were included. Univariate and multivariate Cox regression was performed to determine the risk factors for all-cause mortality. Classification and regression tree analysis was performed to identify the relative importance of these risk factors. RESULTS: 3,573 patients were included in the study. Overall mortality rate was 25.7%. In-hospital mortality rate was 1.62% overall. 30-day, 1-year, 5-year, 10-year and 14.5-year mortality rates were 1.46%, 2.94%, 9.89%, 22.79% and 36.30% respectively. Factors associated with death after adjustment for other risk factors were older age, lower body mass index (BMI), hypertension, diabetes mellitus, chronic obstructive pulmonary disease, pre-operative renal failure on dialysis, higher last pre-operative creatinine level, lower estimated glomerular filtration rate (eGFR), heart failure, lower left ventricular ejection fraction and New York Heart Association class II, III and IV. Additionally, female gender and logistic EuroSCORE were associated with death on univariate Cox analysis, but not associated with death after adjustment with multivariate Cox analysis. Using CART analysis, the strongest predictor of mortality was pre-operative eGFR < 46.9, followed by logistic EuroSCORE ≥ 2.4. CONCLUSION: Poorer renal function, quantified by a lower eGFR, is the best predictor of post-CABG mortality. Amongst other risk factors, logistic EuroSCORE, age, diabetes and BMI had a relatively greater impact on mortality. Patients with chronic kidney disease stage 3B and above are at highest risk for mortality. We hope these findings heighten awareness to optimise current medical therapy in preserving renal function upon diagnosis of any atherosclerotic disease and risk factors contributing to coronary artery disease.

Cardiovascular events after invasive pneumococcal disease: a retrospective cohort study.

OBJECTIVES: This study aims to understand the magnitude of and mechanisms underlying the development of cardiovascular events (CVEs) in patients with invasive pneumococcal disease (IPD). We aimed to identify factors that contribute to the occurrence of CVEs within one year after admission and discuss implications for patient care. METHODS: A multicentered cohort study, including adult patients from four Dutch hospitals who had a positive blood culture for S. pneumoniae and any type of clinical manifestation between 2012-2020. Disease characteristics and microbiological data were systematically collected from electronic patient files. Main outcome measures were the occurrence of stroke and acute coronary syndromes (ACS). RESULTS: Of 914 eligible patients, 4.2% experienced a CVE within one year after admission for IPD. ACS mainly occurred in the first two weeks, whereas stroke developed throughout follow-up. While ACS were positively associated with disease severity, the sole independent predictor was alcohol abuse (OR 3.840, 95% CI 1.108-13.303). Although stroke occurred in 6.3% of meningitis cases, the best clinical predictor of stroke was a body temperature >39.5°C at admission (OR 3.117 (1.154-8.423). In the adult IPD population <70 years old, pneumococcal serotypes were the primary predictors of ACS (7F; OR 15.733 (1.812-136.632)) and stroke (22F; OR 7.320 (1.193-44.903)). CONCLUSION: Adverse cardiovascular events were not uncommon after IPD diagnosis and deserve attention, especially in the high risk groups we identified in our study population. Whether specific serotypes play a role in the development towards CVE requires substantiation in further research.

The Asian Fabry Cardiomyopathy High-Risk Screening Study 2 (ASIAN-FAME-2): Prevalence of Fabry Disease in Patients with Left Ventricular Hypertrophy.

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder that commonly manifests cardiovascular complications. We aimed to assess the prevalence of FD in a Chinese population with left ventricular hypertrophy (LVH) whilst implementing a gender-specific screening approach. Methods: Patients with LVH, defined as a maximum thickness of the left ventricular septal/posterior wall ≥ 13 mm, were considered eligible. All patients with hypertrophic cardiomyopathy (HCM) were excluded. Plasma α-galactosidase (α-GLA) enzyme activity was assessed using a dried blood spot test. Males with low enzyme activity underwent genetic testing to confirm a diagnosis of FD whereas females were screened for both α-GLA and globotriaosylsphingosine concentration and underwent genetic analysis of the GLA gene only if testing positive for ≥1 parameter. Results: 426 unrelated patients (age = 64.6 ± 13.0 years; female: male = 113:313) were evaluated. FD was diagnosed in 3 unrelated patients (age = 69.0 ± 3.5 years, female: male = 1:2) and 1 related female subject (age = 43 years). Genetic analyses confirmed the late-onset cardiac variant GLA c.640-801G>A (n = 3) and the missense variant c.869T>C associated with classic FD (n = 1). Cardiac complications were the only significant findings associated with the late-onset c.640-801G>A mutation, manifesting as mild or severe concentric LVH. In contrast, the classic c.869T>C mutation FD exhibited multisystemic manifestations in addition to severe concentric LVH. Conclusions: The prevalence of FD is lower in Chinese patients with LVH when HCM is excluded. The pathological variant c.640-801G>A remains the most common cause of late-onset FD, while the detection of FD in females can be improved by utilizing a gender-specific screening method.

Long-term impact of basin-wide wastewater management on faecal pollution levels along the entire Danube River.

The Danube River is, at 2857 km, the second longest river in Europe and the most international river in the world with 19 countries in its catchment. Along the entire river, faecal pollution levels are mainly influenced by point-source emissions from treated and untreated sewage of municipal origin under base-flow conditions. In the past 2 decades, large investments in wastewater collection and treatment infrastructure were made in the European Union (EU) Member States located in the Danube River Basin (DRB). Overall, the share of population equivalents with appropriately biologically treated wastewater (without disinfection) has increased from 69% to more than 85%. The proportion of tertiary treatment has risen from 46 to 73%. In contrast, no comparable improvements of wastewater infrastructure took place in non-EU Member States in the middle and lower DRB, where a substantial amount of untreated wastewater is still directly discharged into the Danube River. Faecal pollution levels along the whole Danube River and the confluence sites of the most important tributaries were monitored during four Danube River expeditions, the Joint Danube Surveys (JDS). During all four surveys, the longitudinal patterns of faecal pollution were highly consistent, with generally lower levels in the upper section and elevated levels and major hotspots in the middle and lower sections of the Danube River. From 2001 to 2019, a significant decrease in faecal pollution levels could be observed in all three sections with average reduction rates between 72 and 86%. Despite this general improvement in microbiological water quality, no such decreases were observed for the highly polluted stretch in Central Serbia. Further improvements in microbiological water quality can be expected for the next decades on the basis of further investments in wastewater infrastructure in the EU Member States, in the middle and lower DRB. In the upper DRB, and due to the high compliance level as regards collection and treatment, improvements can further be achieved by upgrading sewage treatment plants with quaternary treatment steps as well as by preventing combined sewer overflows. The accession of the Western Balkan countries to the EU would also significantly boost investments in wastewater infrastructure and water quality improvements in the middle section of the Danube. Continuing whole-river expeditions such as the Joint Danube Surveys is highly recommended to monitor the developments in water quality in the future.

Multikingdom and functional gut microbiota markers for autism spectrum disorder.

Associations between the gut microbiome and autism spectrum disorder (ASD) have been investigated although most studies have focused on the bacterial component of the microbiome. Whether gut archaea, fungi and viruses, or function of the gut microbiome, is altered in ASD is unclear. Here we performed metagenomic sequencing on faecal samples from 1,627 children (aged 1-13 years, 24.4% female) with or without ASD, with extensive phenotype data. Integrated analyses revealed that 14 archaea, 51 bacteria, 7 fungi, 18 viruses, 27 microbial genes and 12 metabolic pathways were altered in children with ASD. Machine learning using single-kingdom panels showed area under the curve (AUC) of 0.68 to 0.87 in differentiating children with ASD from those that are neurotypical. A panel of 31 multikingdom and functional markers showed a superior diagnostic accuracy with an AUC of 0.91, with comparable performance for males and females. Accuracy of the model was predominantly driven by the biosynthesis pathways of ubiquinol-7 or thiamine diphosphate, which were less abundant in children with ASD. Collectively, our findings highlight the potential application of multikingdom and functional gut microbiota markers as non-invasive diagnostic tools in ASD.

Variants in Vitamin D-related Genes and Prostate Cancer Risk in Black Men.

BACKGROUND: The relationship between vitamin D and prostate cancer has primarily been characterized among White men. However, Black men have higher prostate cancer incidence and mortality rates, chronically low circulating vitamin D levels, and ancestry-specific genetic variants in vitamin D-related genes. Here, we examine six critical genes in the vitamin D pathway and prostate cancer risk in Black men. METHODS: We assessed a total of 69 candidate variants in six genes ( GC, CYP27A1, CYP27B1, CYP24A1, VDR , and RXRA ) including functional variants previously associated with prostate cancer and circulating 25(OHD) in White men. Associations with prostate cancer risk were examined using genome-wide association study data for approximately 10,000 prostate cancer cases and 10,000 controls among Black men and over 85,000 cases and 91,000 controls among White men. A statistical significance threshold of 0.000724 was used to account for the 69 variants tested. RESULTS: None of the variants examined were significantly associated with prostate cancer risk among Black men after multiple comparison adjustment. Four variants tested P<0.05 in Black men, including two in RXRA (rs41400444 OR=1.09, 95% CI: 1.01-1.17, P = 0.024 and rs10881574 OR = 0.93, 0.87-1.00, P = 0.046) and two in VDR (rs2853563 OR = 1.07, 1.01-1.13, P = 0.017 and rs1156882 OR = 1.06, 1.00-1.12, P = 0.045). Two variants in VDR were also positively associated with risk in White men (rs11568820 OR = 1.04, 1.02-1.06, P = 0.00024 and rs4516035 OR = 1.03, 1.01-1.04, P = 0.00055). CONCLUSION: We observed suggestive non-significant associations between genetic variants in RXRA and VDR and prostate cancer risk in Black men. Future research exploring the relationship of vitamin D with cancer risk in Black men will need larger sample sizes to identify ancestry-specific variants relevant to risk in this population.

Suicidal ideation among non-physician hospital system staff: Prevalence and workplace correlates.

BACKGROUND: Research suggests that healthcare workers are at greater risk for suicide than other occupations, but most published studies focus on physicians. This study examines the prevalence of suicidal ideation (SI) and associated occupational factors among a broad group of non-physician healthcare staff. METHODS: An anonymous online survey was sent to a random sample of 30 % of non-physician healthcare staff at a large urban healthcare system between September and November 2022. Weighted multivariable binary logistic regressions were conducted to determine the workplace and mental health factors associated with SI. RESULTS: The 1084 respondents included nurses, administrative staff, research staff, medical assistants, nurse practitioners, physician assistants, and other roles. Of the sample, 8.8 % endorsed having SI over the prior two weeks. Results of the regression indicated that, after adjusting for demographic factors, greater odds of SI were associated with physical violence experienced from a patient or visitor (odds ratio [OR] = 2.15, 95 % confidence interval [CI] = 1.06-4.37), lower perceived leadership support (OR = 0.95, 95 % CI = 0.92-0.98), and positive screening for depression (OR = 4.66, 95 % CI = 2.45-8.86). Exploratory analysis suggests that depression may be a mediating factor between workplace stressors and SI. LIMITATIONS: Limitations include the response rate, the use of a single item to assess SI, and the cross-sectional design. CONCLUSION: Findings suggest that workplace violence and leadership support are important occupational factors associated with SI among healthcare workers. Reducing and mitigating workplace violence, enhancing leadership support, and improving access to mental health care should be considered targets for interventions to decrease suicide risk in this population.

Mucosal Melanoma of Palate: A Case Report with Review of Literature.

The World Health Organisation defines mucosal malignant melanoma as a malignant tumour of melanocytes or of melanocyte progenitors. Due to the lack of symptoms and unknown etiology, mucosal malignant melanoma may go undiagnosed. The surgeon can find it challenging to come up with a definitive treatment strategy because of its rarity and rapid spread. In this case study, a 57-year-old female patient with hyperpigmented gingiva and palate diagnosed pathologically and immunohistochemically as malignant melanoma underwent surgical excision and a modified radical neck dissection.

Substance use and mental health factors associated with self-reported higher risk cannabis use among people with HIV screened in primary care.

Background: While cannabis use is prevalent among people with HIV (PWH), factors associated with higher-risk use require further study. We examined factors associated with indicators risk for cannabis use disorder (CUD) among PWH who used cannabis. Methods: Participants included adult (≥18 years old) PWH from 3 HIV primary care clinics in Kaiser Permanente Northern California who reported past three-month cannabis use through the computerized Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) screening. Primary outcome was TAPS cannabis score (range 1-3), categorized as any use (1) and higher risk for CUD (≥2). Measures included sociodemographics (age, sex, race, neighborhood deprivation index [NDI]), Charlson Comorbidity Index (CCI), HIV RNA, CD4 cell counts, higher risk tobacco use (TAPS tobacco score≥2), depression, and anxiety symptoms. Unadjusted and multivariable logistic regression examined factors associated with higher risk for CUD. Results: Of the complete sample (N=978; 94.1% Male; 58.3% White; Age Mode=51-60), 35.8% reported higher risk for CUD. Unadjusted models indicated younger age, Black race, higher CCI, depression, anxiety, and higher risk tobacco use were associated with higher risk, while only Black race (OR=1.84, 95% CI[1.29, 2.63]), anxiety (OR=1.91, 95% CI[1.22, 2.98]), and higher risk tobacco use (OR=2.27, 95% CI[1.47, 3.51]) remained significant in the multivariable model. Conclusions: Black race, anxiety and tobacco use, but not HIV clinical markers, were associated with higher risk for CUD among PWH. Clinical efforts to screen and provide interventions for preventing CUD alongside anxiety and tobacco use among PWH should be evaluated.

AMPK-mediated regulation of endogenous cholesterol synthesis does not affect atherosclerosis in a murine Pcsk9-AAV model.

BACKGROUND AND AIMS: Dysregulated cholesterol metabolism is a hallmark of atherosclerotic cardiovascular diseases, yet our understanding of how endogenous cholesterol synthesis affects atherosclerosis is not clear. The energy sensor AMP-activated protein kinase (AMPK) phosphorylates and inhibits the rate-limiting enzyme in the mevalonate pathway HMG-CoA reductase (HMGCR). Recent work demonstrated that when AMPK-HMGCR signaling was compromised in an Apoe-/- model of hypercholesterolemia, atherosclerosis was exacerbated due to elevated hematopoietic stem and progenitor cell mobilization and myelopoiesis. We sought to validate the significance of the AMPK-HMGCR signaling axis in atherosclerosis using a non-germline hypercholesterolemia model with functional ApoE. METHODS: Male and female HMGCR S871A knock-in (KI) mice and wild-type (WT) littermate controls were made atherosclerotic by intravenous injection of a gain-of-function Pcsk9D374Y-adeno-associated virus followed by high-fat and high-cholesterol atherogenic western diet feeding for 16 weeks. RESULTS: AMPK activation suppressed endogenous cholesterol synthesis in primary bone marrow-derived macrophages from WT but not HMGCR KI mice, without changing other parameters of cholesterol regulation. Atherosclerotic plaque area was unchanged between WT and HMGCR KI mice, independent of sex. Correspondingly, there were no phenotypic differences observed in hematopoietic progenitors or differentiated immune cells in the bone marrow, blood, or spleen, and no significant changes in systemic markers of inflammation. When lethally irradiated female mice were transplanted with KI bone marrow, there was similar plaque content relative to WT. CONCLUSIONS: Given previous work, our study demonstrates the importance of preclinical atherosclerosis model comparison and brings into question the importance of AMPK-mediated control of cholesterol synthesis in atherosclerosis.

Genome-wide association study for milking speed in Fleckvieh cattle.

Milking speed is an important trait influencing udder health of dairy cows as well as labor efficiency. Yet, it has received little attention in genomic association studies. The main objective of this study was to determine regions and genes on the genome with a potential effect on milking speed in Fleckvieh (dual purpose Simmental) cattle. Genome-wide association studies were conducted using de-regressed breeding values of bulls as phenotypes. Six SNP on 4 autosomes were significantly associated with milking speed for additive effects. Significant regions on BTA4 and BTA19 correspond with findings for other dairy cattle breeds. Based on the observation of Fleckvieh breed managers, variation of milking speed in batches of daughters of some bulls is much higher than in daughter groups of other bulls. This difference in within family variation may be caused by transmission of alternative alleles of bulls being heterozygous for a gene affecting milking speed. To check on this, we considered standard deviation of yield deviations in milking speed of half-sib daughters as a new trait and performed GWAS for dominance effects. One signal on BTA5 passed the genome wide Bonferroni threshold that corresponded to the significant signal from standard GWAS on de-regressed breeding values. The key conclusion of this study is that several strong genomic signals were found for milking speed in Fleckvieh cattle and that the strongest of them are supported by similar findings in Brown Swiss and Holstein Friesian cattle. Milking speed is a complex trait whose sub-processes have not yet been elucidated in detail. Hence, it remains a challenge to link the associated regions on the genome with causal genes and their functions.

A meta-analysis of randomized controlled clinical trials for implications of acute treatment effects on glomerular filtration rate for long-term kidney protection.

Pharmacologic interventions to slow chronic kidney disease progression, such as ACE-inhibitors, angiotensin receptor blockers, or sodium glucose co-transporter 2 inhibitors, often produce acute treatment effects on glomerular filtration rate (GFR) that differ from their long-term chronic treatment effects. Observational studies assessing the implications of acute effects cannot distinguish acute effects from GFR changes unrelated to the treatment. Here, we performed meta-regression analysis of multiple trials to isolate acute effects to determine their long-term implications. In 64 randomized controlled trials (RCTs), enrolling 154,045 participants, we estimated acute effects as the mean between-group difference in GFR slope from baseline to three months, effects on chronic GFR slope (starting at three months after randomization), and effects on three composite kidney endpoints defined by kidney failure (GFR 15 ml/min/1.73m2 or less, chronic dialysis, or kidney transplantation) or sustained GFR declines of 30%, 40% or 57% decline, respectively. We used Bayesian meta-regression to relate acute effects with treatment effects on chronic slope and the composite kidney endpoints. Overall, acute effects were not associated with treatment effects on chronic slope. Acute effects were associated with the treatment effects on composite kidney outcomes such that larger negative acute effects were associated with lesser beneficial effects on the composite kidney endpoints. Associations were stronger when the kidney composite endpoints were defined by smaller thresholds of GFR decline (30% or 40%). Results were similar in a subgroup of interventions with supposedly hemodynamic effects that acutely reduce GFR. For studies with GFR 60 mL/min/1.73m2 or under, negative acute effects were associated with larger beneficial effects on chronic GFR slope. Thus, our data from a large and diverse set of RCTs suggests that acute effects of interventions may influence the treatment effect on clinical kidney outcomes.

Beyond overlap: Considering habitat preference and fitness outcomes in the umbrella species concept.

Umbrella species and other surrogate-species approaches to conservation provide an appealing framework to extend the reach of conservation efforts beyond single species. For the umbrella species concept to be effective, populations of multiple species of concern must persist in areas protected on behalf of the umbrella species. Most assessments of the concept, however, focus exclusively on geographic overlap among umbrella and background species, and not measures that affect population persistence (e.g., habitat quality or fitness). We quantified the congruence between the habitat preferences and nesting success of a high-profile umbrella species (greater sage-grouse, Centrocercus urophasianus, hereafter "sage-grouse"), and three sympatric species of declining songbirds (Brewer's sparrow Spizella breweri, sage thasher Oreoscoptes montanus, and vesper sparrow Pooecetes gramineus) in central Wyoming, USA during 2012 - 2013. We used machine-learning methods to create data-driven predictions of sage-grouse nest-site selection and nest survival probabilities by modeling field-collected sage-grouse data relative to habitat attributes. We then used field-collected songbird data to assess whether high-quality sites for songbirds aligned with those of sage-grouse. Nest sites selected by songbirds did not coincide with sage-grouse nesting preferences, with the exception that Brewer's sparrows preferred similar nest sites to sage-grouse in 2012. Moreover, the areas that produced higher rates of songbird nest survival were unrelated to those for sage-grouse. Our findings suggest that management actions at local scales that prioritize sage-grouse nesting habitat will not necessarily enhance the reproductive success of sagebrush-associated songbirds. Measures implemented to conserve sage-grouse and other purported umbrella species at broad spatial scales likely overlap the distribution of many species, however, broad-scale overlap may not translate to fine-scale conservation benefit beyond the umbrella species itself. The maintenance of microhabitat heterogeneity important for a diversity of species of concern will be critical for a more-holistic application of the umbrella species concept.