Identification of single-site gold catalysis in acetylene hydrochlorination

There remains considerable debate over the active form of gold under operating conditions of a recently validated gold catalyst for acetylene hydrochlorination. We have performed an in situ x-ray absorption fine structure study of gold/carbon (Au/C) catalysts under acetylene hydrochlorination reaction conditions and show that highly active catalysts comprise single-site cationic Au entities whose activity correlates with the ratio of Au(I):Au(III) present. We demonstrate that these Au/C catalysts are supported analogs of single-site homogeneous Au catalysts and propose a mechanism, supported by computational modeling, based on a redox couple of Au(I)-Au(III) species. View Full Tex

Tissue-specific patterns of allelically-skewed DNA methylation

While DNA methylation is usually thought to be symmetrical across both alleles, there are some notable exceptions. Genomic imprinting and X chromosome inactivation are two well-studied sources of allele-specific methylation (ASM), but recent research has indicated a more complex pattern in which genotypic variation can be associated with allelically-skewed DNA methylation in cis. Given the known heterogeneity of DNA methylation across tissues and cell types we explored inter- and intra-individual variation in ASM across several regions of the human brain and whole blood from multiple individuals. Consistent with previous studies, we find widespread ASM with >4% of the ~220,000 loci interrogated showing evidence of allelically-skewed DNA methylation. We identify ASM flanking known imprinted regions, and show that ASM sites are enriched in DNase I hypersensitivity sites and often located in an extended genomic context of intermediate DNA methylation. We also detect examples of genotype-driven ASM, some of which are also tissue-specific. These findings contribute to our understanding about the nature of differential DNA methylation across tissues and have important implications for genetic studies of complex disease. As a resource to the community, ASM patterns across each of the tissues studied are available in a searchable online database: http://epigenetics.essex.ac.uk/ASMBrainBlood

Changes in physical activity during hospital admission for chronic respiratory disease: Inpatient step count does not recover

Background and objectiveEstablishing the amount of inpatient physical activity (PA) undertaken by individuals hospitalized for chronic respiratory disease is needed to inform interventions. This observational study investigated whether PA changes when a person is an inpatient, how long is required to obtain representative PA measures and whether PA varies within a day and between patients of differing lengths of stay.MethodsA total of 389 participants were recruited as early as possible into their hospitalization. Patients wore a PA monitor from recruitment until discharge. Step count was extracted for a range of wear time criteria. Single‐day intraclass correlation coefficients (ICC) were calculated, with an ICC ≥ 0.80 deemed acceptable.ResultsPA data were available for 259 participants. No changes in daily step count were observed during the inpatient stay (586 (95% CI: 427–744) vs 652 (95% CI: 493–812) steps/day for day 2 and 7, respectively). ICC across all wear time criteria were > 0.80. The most stringent wear time criterion, retaining 80% of the sample, was ≥11 h on ≥1 day. More steps were taken during the morning and afternoon than overnight and evening. After controlling for the Medical Research Council (MRC) grade or oxygen use, there was no difference in step count between patients admitted for 2–3 days (short stay) and those admitted for 7–14 days (long stay).ConclusionPatients move little during their hospitalization, and inpatient PA did not increase during their stay. A wear time criterion of 11 waking hours on any single day was representative of the entire admission whilst retaining an acceptable proportion of the initial sample size. Patients may need encouragement to move more during their hospital stay

Baseline Chromatin Modification Levels May Predict Interindividual Variability in Ozone-Induced Gene Expression

Traditional toxicological paradigms have relied on factors such as age, genotype, and disease status to explain variability in responsiveness to toxicant exposure; however, these are neither sufficient to faithfully identify differentially responsive individuals nor are they modifiable factors that can be leveraged to mitigate the exposure effects. Unlike these factors, the epigenome is dynamic and shaped by an individual’s environment. We sought to determine whether baseline levels of specific chromatin modifications correlated with the interindividual variability in their ozone (O3)-mediated induction in an air–liquid interface model using primary human bronchial epithelial cells from a panel of 11 donors. We characterized the relationship between the baseline abundance of 6 epigenetic markers with established roles as key regulators of gene expression—histone H3 lysine 4 trimethylation (H3K4me3), H3K27 acetylation (H3K27ac), pan-acetyl H4 (H4ac), histone H3K27 di/trimethylation (H3K27me2/3), unmodified H3, and 5-hydroxymethylcytosine (5-hmC)—and the variability in the O3-induced expression of IL-8, IL-6, COX2, and HMOX1. Baseline levels of H3K4me3, H3K27me2/3, and 5-hmC, but not H3K27ac, H4ac, and total H3, correlated with the interindividual variability in O3-mediated induction of HMOX1 and COX2. In contrast, none of the chromatin modifications that we examined correlated with the induction of IL-8 and IL-6. From these findings, we propose an “epigenetic seed and soil” model in which chromatin modification states between individuals differ in the relative abundance of specific modifications (the “soil”) that govern how receptive the gene is to toxicant-mediated cellular signals (the “seed”) and thus regulate the magnitude of exposure-related gene induction

Phylogeny of the Australian Solanum dioicum group using seven nuclear genes: Testing Symon’s fruit and seed dispersal hypotheses.

The dioecious and andromonoecious Solanum taxa (the “S. dioicum group”) of the Australian Monsoon Tropics have been the subject of phylogenetic and taxonomic study for decades, yet much of their basic biology is still unknown. This is especially true for plant-animal interactions, including the influence of fruit form and calyx morphology on seed dispersal. We combine field/greenhouse observations and specimen-based study with phylogenetic analysis of seven nuclear regions obtained via a microfluidic PCR-based enrichment strategy and high-throughput sequencing, and present the first species-tree hypothesis for the S. dioicum group. Our results suggest that epizoochorous trample burr seed dispersal (strongly linked to calyx accrescence) is far more common among Australian Solanum than previously thought and support the hypothesis that the combination of large fleshy fruits and endozoochorous dispersal represents a reversal in this study group. The general lack of direct evidence related to biotic dispersal (epizoochorous or endozoochorous) may be a function of declines and/or extinctions of vertebrate dispersers. Because of this, some taxa might now rely on secondary dispersal mechanisms (e.g. shakers, tumbleweeds, rafting) as a means to maintain current populations and establish new ones

Real-World Concordance between Germline and Tumour <i>BRCA1/2</i> Status in Epithelial Ovarian Cancer

Patients diagnosed with epithelial ovarian cancer may undergo reflex tumour BRCA1/ 2 testing followed by germline BRCA1/2 testing in patients with a positive tumour test result. This testing model relies on tumour BRCA1/ 2 tests being able to detect all types of pathogenic variant. We analysed germline and tumour BRCA1/2 test results from patients treated for epithelial ovarian cancer at our specialist oncological referral centre. Tumour BRCA1/2 testing was performed using the next-generation sequencing (NGS)-based myChoice ® companion diagnostic (CDx; Myriad Genetics, Inc.). Germline BRCA1/2 testing was performed in the North West Genomic Laboratory Hub using NGS and multiplex ligation-dependent probe amplification. Between 11 April 2021 and 11 October 2023, 382 patients were successfully tested for tumour BRCA1 and BRCA2 variants. Of these, 367 (96.1%) patients were tested for germline BRCA1/ 2 variants. In those patients who underwent tumour and germline testing, 15.3% (56/367) had a BRCA1/ 2 pathogenic variant (36 germline and 20 somatic). All germline BRCA1/2 pathogenic small sequencing variants were detected in tumour DNA. By contrast, 3 out of 8 germline BRCA1/2 pathogenic large rearrangements were not reported in tumour DNA. The overall concordance of germline BRCA1/2 pathogenic variants detected in germline and tumour DNA was clinically acceptable at 91.7% (33/36). The myChoice ® CDx was able to detect most germline BRCA1/2 pathogenic variants in tumour DNA, although a proportion of pathogenic large rearrangements were not reported. If Myriad's myChoice ® CDx is used for tumour BRCA1/2 testing, our data supports a testing strategy of germline and tumour BRCA1/2 testing in all patients diagnosed with epithelial ovarian cancer aged &lt; 79 years old, with germline BRCA1/2 testing only necessary for patients aged ≥ 80 years old with a tumour BRCA1/2 pathogenic variant. </p

Effective Leadership of Surgical Teams: A Mixed Methods Study of Surgeon Behaviors and Functions.

BACKGROUND: The importance of effective team leadership for achieving surgical excellence is widely accepted, but we understand less about the behaviors that achieve this goal. We studied cardiac surgical teams to identify leadership behaviors that best support surgical teamwork. METHODS: We observed, surveyed, and interviewed cardiac surgical teams, including 7 surgeons and 116 team members, from September 2013 to April 2015. We documented 1,926 surgeon/team member interactions during 22 cases, coded them by behavior type and valence (ie, positive/negative/neutral), and characterized them by leadership function (conductor, elucidator, delegator, engagement facilitator, tone setter, being human, and safe space maker) to create a novel framework of surgical leadership derived from direct observation. We surveyed nonsurgeon team members about their perceptions of individual surgeon's leadership effectiveness on a 7-point Likert scale and correlated survey measures with individual surgeon profiles created by calculating percentage of behavior types, leader functions, and valence. RESULTS: Surgeon leadership was rated by nonsurgeons from 4.2 to 6.2 (mean, 5.4). Among the 33 types of behaviors observed, most interactions constituted elucidating (24%) and tone setting (20%). Overall, 66% of interactions (range, 43%-84%) were positive and 11% (range, 1%-45%) were negative. The percentage of positive and negative behaviors correlated strongly (r = 0.85 for positive and r = 0.75 for negative, p < 0.05) with nonsurgeon evaluations of leadership. Facilitating engagement related most positively (r = 0.80; p = 0.03), and negative forms of elucidating, ie, criticism, related most negatively (r = -0.81; p = 0.03). CONCLUSIONS: We identified 7 surgeon leadership functions and related behaviors that impact perceptions of leadership. These observations suggest actionable opportunities to improve team leadership behavior.Authors acknowledge funding from CRICO/Risk Management Foundation (#225243), MGH’s Division of Cardiac Surgery, and Wellcome Trust (WT097899M)

Identification of a Ruminant Origin Group B Rotavirus Associated with Diarrhea Outbreaks in Foals

Equine rotavirus group A (ERVA) is one of the most common causes of foal diarrhea. Starting in February 2021, there was an increase in the frequency of severe watery to hemorrhagic diarrhea cases in neonatal foals in Central Kentucky. Diagnostic investigation of fecal samples failed to detect evidence of diarrhea-causing pathogens including ERVA. Based on Illumina-based metagenomic sequencing, we identified a novel equine rotavirus group B (ERVB) in fecal specimens from the affected foals in the absence of any other known enteric pathogens. Interestingly, the protein sequence of all 11 segments had greater than 96% identity with group B rotaviruses previously found in ruminants. Furthermore, phylogenetic analysis demonstrated clustering of the ERVB with group B rotaviruses of caprine and bovine strains from the USA. Subsequent analysis of 33 foal diarrheic samples by RT-qPCR identified 23 rotavirus B-positive cases (69.69%). These observations suggest that the ERVB originated from ruminants and was associated with outbreaks of neonatal foal diarrhea in the 2021 foaling season in Kentucky. Emergence of the ruminant-like group B rotavirus in foals clearly warrants further investigation due to the significant impact of the disease in neonatal foals and its economic impact on the equine industry

Oestrogen receptor negative early operable primary breast cancer in older women—biological characteristics and long-term clinical outcome

BackgroundOlder women are at the greatest risk of breast cancer development and a considerable number present with comorbidities. Although the majority of breast cancers in this age group express oestrogen receptor (ER), which makes endocrine therapy (primary or adjuvant) feasible, given the huge size of the elderly population, there remains a significant number of patients, in absolute term, whose tumours do not express ER and their management is challenging.MethodsOf a consecutive series of 1,758 older (≥70 years) women with early operable primary breast cancer managed in a dedicated service from 1973–2010, 252(14.3%) had ER-negative (histochemical (H) score ≤50) tumours. Their clinical outcome was retrospectively reviewed and tumour samples collected from diagnostic core biopsies were analysed for progesterone receptor (PgR), HER2 and Ki67 using immunohistochemistry.ResultsThe commonest primary treatment was surgery (N = 194, 77%) followed by primary endocrine therapy (14.3%), primary radiotherapy (5.6%) and supportive treatment only (3.1%). Among the patients undergoing surgery, most of them had grade 3 (78.1%) and node-negative disease (62.2%). Some of them (21.1%) received postoperative radiotherapy. At a median follow-up of 37.5 months, 117 patients had died, out of which 48.6% were due to breast cancer. For those who underwent surgery, the regional and local recurrence rates were 2% and 1.1% per annum respectively. For those who received primary endocrine therapy, 38% progressed at 6 months, however all patients who had primary radiotherapy achieved clinical benefit at 6 months. Regardless of treatment given, the 5-year breast cancer specific and overall survival rates were 70% and 50% respectively. Biological analysis based on good quality needle core biopsy specimensfrom181 patients showed that 26.8% (N = 49), 16.9% (N = 31) and 70.7% (N = 70)expressed positivity for PgR, HER2 and Ki67 respectively. No correlation between these biomarkers and breast cancer specific survival was demonstrated.ConclusionOestrogen receptor negative early operable primary breast cancer in older women is associated with poor prognostic features in terms of biology and clinical outcome. Surgery appears to produce the best outcome as a primary treatment, however for those where neither surgery nor chemotherapy is appropriate, primary radiotherapy can be beneficial