Observing IMBH-IMBH Binary Coalescences via Gravitational Radiation

Recent numerical simulations have suggested the possibility of forming double intermediate mass black holes (IMBHs) via the collisional runaway scenario in young dense star clusters. The two IMBHs formed would exchange into a common binary shortly after their birth, and quickly inspiral and merge. Since space-borne gravitational wave (GW) observatories such as LISA will be able to see the late phases of their inspiral out to several Gpc, and LIGO will be able to see the merger and ringdown out to similar distances, they represent potentially significant GW sources. In this Letter we estimate the rate at which LISA and LIGO will see their inspiral and merger in young star clusters, and discuss the information that can be extracted from the observations. We find that LISA will likely see tens of IMBH--IMBH inspirals per year, while advanced LIGO could see ~10 merger and ringdown events per year, with both rates strongly dependent on the distribution of cluster masses and densities.Comment: Accepted for publication in ApJL. Minor changes to reflect accepted version. 4 pages in emulateapj, 3 figure

Herd health status and management practices on 16 Irish suckler beef farms

peer-reviewedBackground: There have been few studies published internationally which document herd health management practices in suckler beef herds and no published Irish studies. The study objective was to document herd health status and management practices on sixteen Irish suckler beef herds over a two year period (2009–2010). The farms used in the study were part of the Teagasc BETTER farm beef programme. The mean (s.d.) herd size, stocking rate and farm size was 68 cows (27.6), 2.0 LU/ha (0.3) and 64.3 (21.6) adjusted hectares, respectively. Two questionnaires were designed; 1) a farmer questionnaire to collect information on farm background and current herd health control practices and 2) a veterinary questionnaire to collect information on the extent of animal health advice given by veterinarians to their clients and identification of any on-farm herd health issues. Results: Dystocia, calf pneumonia, and calf diarrhoea, in that order, were identified as the primary herd health issues in these Irish suckler beef herds. In addition, substantial deficiencies in biosecurity practices were also identified on these farms. Conclusions: The findings of this study may serve as the focus for future research in animal health management practices in Irish suckler beef herds

Nematode control in suckler beef cattle over their first two grazing seasons using a targeted selective treatment approach

peer-reviewedBackground With concerns over the development of anthelmintic resistance in cattle nematode populations, we must re-examine our approach to nematode control in cattle. Targeted selective treatments (TST), whereby individual animals are treated instead of entire groups, are being investigated as an alternative. The study objective was to determine if anthelmintic usage could be reduced using a TST-based approach to nematode control in spring-born suckler beef cattle over their first and second grazing seasons (SGS) without affecting performance. In the first grazing season (FGS), 99 calves with an initial mean (s.d.) calf age and live weight on day 0 (June 28th 2012) of 107 (23.1) days and 160 (32.5) kg, respectively, were used. The study commenced on day 0 when calves were randomised and allocated to one of two treatments; 1), standard treatment (control) and 2), TST. Control calves were treated subcutaneously with ivermectin on days 0, 41 and 82 in the FGS. All calves were treated with ivermectin on day 124 and housed on day 133. In the SGS, only heifer calves from the FGS were used and control heifers were treated with ivermectin on day 393. Animals were weighed, blood and faecal sampled every three weeks. The TST animals were treated with ivermectin if thresholds based on a combination of plasma pepsinogen concentrations, faecal egg count and/or the presence of Dictyocaulus viviparus larvae in faeces (FGS only) were reached. Results No TST calves reached the treatment threshold criteria in the FGS. The FGS average daily live weight gain (ADG ± s.e.m.) for control and TST group calves was 0.89 ± 0.02 kg and 0.94 ± 0.02 kg day−1, respectively (P = 0.17). In the SGS, all heifers were treated with ivermectin on day 431 due to clinical signs of respiratory disease. The ADG for control and TST heifers from turnout on day 321 to day 431 was 0.90 ± 0.04 and 0.80 ± 0.04 kg day−1, respectively (P = 0.03). Conclusions Spring-born FGS suckler beef calves require minimal anthelmintic treatment to maintain performance. In contrast, clinical parasitic disease may develop in the SGS unless appropriate anthelmintic treatment is provided

Identifying Ethical Hypernorms For Accounting Educators

Accounting educators have a unique role in academe because students learn about codes of ethics that will guide their actions as professionals. We identify hypernorms related to internal auditing educators that reflect unethical behaviors believed to be universally unacceptable by that community. We then compare the results to a prior survey of accounting educators and identify ethical principles for accounting academics in their roles as teachers and researchers. The results might help to develop a code of ethics for accounting educators to help them serve as role models for students as they prepare to enter the accounting profession

Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice.

In recent years oral mucosal injury has been increasingly recognized as an important toxicity associated with mammalian target of rapamycin (mTOR) inhibitors, including in patients with breast cancer who are receiving everolimus. This review addresses the state-of-the-science regarding mTOR inhibitor-associated stomatitis (mIAS), and delineates its clinical characteristics and management. Given the clinically impactful pain associated with mIAS, this review also specifically highlights new research focusing on the study of the molecular basis of pain. The incidence of mIAS varies widely (2-78%). As reported across multiple mTOR inhibitor clinical trials, grade 3/4 toxicity occurs in up to 9% of patients. Managing mTOR-associated oral lesions with topical oral, intralesional, and/or systemic steroids can be beneficial, in contrast to the lack of evidence supporting steroid treatment of oral mucositis caused by high-dose chemotherapy or radiation. However, steroid management is not uniformly efficacious in all patients receiving mTOR inhibitors. Furthermore, technology does not presently exist to permit clinicians to predict a priori which of their patients will develop these lesions. There thus remains a strategic need to define the pathobiology of mIAS, the molecular basis of pain, and risk prediction relative to development of the clinical lesion. This knowledge could lead to novel future interventions designed to more effectively prevent mIAS and improve pain management if clinically significant mIAS lesions develop

Chronic activation of Toll-like receptor 2 induces an ichthyotic skin phenotype

BACKGROUND: Ichthyosis defines a group of chronic conditions that manifest phenotypically as a thick layer of scales and often affects the entire skin. While the gene mutations that lead to ichthyosis are well documented, the actual signalling mechanisms that lead to scaling are poorly characterised, however recent publications suggest that there are common mechanisms active in ichthyotic tissue, and in analogous models of ichthyosis. OBJECTIVE: To determine common mechanisms of hyperkeratosis that may be easily targeted with small molecule inhibitors. METHODS: We combined gene expression analysis of gene-specific shRNA knockdowns in rat epidermal keratinocytes of two genes mutated in autosomal recessive congenital ichthyosis (ARCI), Transglutaminase 1 (TGM1) and arachidonate 12-lipoxygenase, 12R type (ALOX12B), and proteomic analysis of skin scale from ARCI patients.as well as RNAseq data from rat epidermal keratinocytes treated with the Toll-like receptor-2 agonist PAM3CSK. RESULTS: we identified a common activation of the Toll-like receptor (TLR) 2 pathway. Exogenous TLR2 activation led to increased expression of important cornified envelope genes and in organotypic culture caused hyperkeratosis. Conversely, blockade of TLR2 signalling in ichthyosis patient keratinocytes and our shRNA models reduced the expression of keratin 1, a structural protein over-expressed in ichthyosis scale. A time-course of Tlr2 activation in rat epidermal keratinocytes revealed that although there was rapid initial activation of innate immune pathways, this was rapidly superseded by widespread up-regulation of epidermal differentiation related proteins. Both NFκβ phosphorylation and Gata3 up-regulation was associated with this switch and Gata3 overexpression was sufficient to increase Keratin 1 expression. CONCLUSION: Taken together, these data define a dual role for Toll-like receptor 2 activation during epidermal barrier repair, that may be a useful therapeutic modality in treating diseases of epidermal barrier dysfunction

Combinations of Maternal KIR and Fetal HLA-C Genes Influence the Risk of Preeclampsia and Reproductive Success

Preeclampsia is a serious complication of pregnancy in which the fetus receives an inadequate supply of blood due to failure of trophoblast invasion. There is evidence that the condition has an immunological basis. The only known polymorphic histocompatibility antigens on the fetal trophoblast are HLA-C molecules. We tested the idea that recognition of these molecules by killer immunoglobulin receptors (KIRs) on maternal decidual NK cells is a key factor in the development of preeclampsia. Striking differences were observed when these polymorphic ligand: receptor pairs were considered in combination. Mothers lacking most or all activating KIR (AA genotype) when the fetus possessed HLA-C belonging to the HLA-C2 group were at a greatly increased risk of preeclampsia. This was true even if the mother herself also had HLA-C2, indicating that neither nonself nor missing-self discrimination was operative. Thus, this interaction between maternal KIR and trophoblast appears not to have an immune function, but instead plays a physiological role related to placental development. Different human populations have a reciprocal relationship between AA frequency and HLA-C2 frequency, suggesting selection against this combination. In light of our findings, reproductive success may have been a factor in the evolution and maintenance of human HLA-C and KIR polymorphisms

In utero exposures to perfluoroalkyl substances and the human fetal liver metabolome in Scotland : a cross-sectional study

The Fetal Human study was funded by the UK Medical Research Council (MR/L010011/1) to PAF, PJO’S, JPI, DCH, and AD, by the Seventh Framework Programme of the European Union under Grant Agreement 212885, and by NHS Grampian Endowments grants (08/02, 09/12, 13/56, and 15/1/010) to PAF. The metabolomics and exposomics study was supported by the Swedish Research Council (to TH and MO; grants 2016-05176 and 2020-03674), Formas (to TH and MO; grant 2019-00869), Novo Nordisk Foundation (to TH; grant NNF20OC0063971), Research Council of Finland (to MO; grant 333981), the Inflammation in human early life: targeting impacts on life-course health consortium funded by the Horizon Europe Program of the European Union (Grant Agreement 101094099 to MO, TH, and PAF), and the framework of the European Partnership for the Assessment of Risks from Chemicals, and has received funding from the European Union's Horizon Europe research and innovation programme (grant agreement 101057014). Views and opinions expressed are, however, those of the author(s) only and do not necessarily reflect those of the European Union or the Health and Digital Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. The authors would like to thank (1) the Fowler team members, NHS Grampian research nurses, and staff at the Pregnancy Counselling Service for their essential work in recruiting, collecting, and processing fetuses; and (2) the Centre for Genome Enabled Biology and Medicine, University of Aberdeen, for carrying out the RNA-Seq. The RNA-Seq data analysis was supported by use of the University of Aberdeen Maxwell High Performance Computer Cluster.Peer reviewedPublisher PD

Disordered alcohol and substance use in Irish farmers: A cross-sectional survey

Purpose Farming is a high-pressure occupation. Populations of farmers face significant health risks, including injury, mental illness, and in some cases, heavy alcohol use. However, there is little research on farmers’ use of substances beyond alcohol. This study examines factors relating to Irish farmers’ disordered alcohol and substance use. Methods In accordance with STROBE guidelines for cross-sectional research and reporting, we examined disordered alcohol and substance use in 351 Irish farmers using the Alcohol Use Disorders Identification Tool (AUDIT) and Drug Use Disorders Identification Tool (DUDIT). Findings While 28% of farmers did not drink, 40% of those who did drink exceeded the AUDIT threshold for disordered use. Similarly, while 95% of farmers did not use substances, 78% of farmers who did use substances exceeded the DUDIT threshold for disordered use. Age was the most important risk factor for disordered alcohol and substance use and correlated with other main risk factors: lower income, no children, part-time farmer, and full-time off-farm roles. Disordered drinking was highest in farmers engaged in full-time education. Conclusions This population of Irish farmers report broadly healthy alcohol and substance use behaviors. Irish farmers may serve as a model group whose strengths can be utilized in interventions within and beyond the Irish farming community. Our results confirm the importance of analyzing demographic factors in farmers’ drinking and identify younger farmers as especially at-risk for harmful alcohol and substance use