The experiences of those who support researchers struggling with their mental health

This international survey examines the nature of the relationships between researchers who struggle with their mental health, and those in the community who try to support them. This work examines who these 'supporters' are, who they help, what they do, and it paints a complex picture of how they feel about this supporting role, and what they need to do it

Kaon mixing beyond the standard model with physical masses

We present non-perturbative results for beyond the standard model kaon mixing matrix elements in the isospin symmetric limit ($m_u=m_d$) of QCD, including a complete estimate of all dominant sources of systematic error. Our results are obtained from numerical simulations of lattice QCD with $N_f = 2+1$ flavours of dynamical domain wall fermions. For the first time, these quantities are simulated directly at the physical pion mass $m_\pi$~$\sim$~$139\,\mathrm{MeV}$ for two different lattice spacings. We include data at three lattice spacings in the range $a = 0.11$ - $0.07\,\mathrm{fm}$ and with pion masses ranging from the physical value up to 450$\,\mathrm{MeV}$. Compared to our earlier work, we have added both direct calculations at physical quark masses and a third lattice spacing making the removal of discretisation effects significantly more precise and eliminating the need for any significant mass extrapolation beyond the range of simulated data. We renormalise the lattice operators non-perturbatively using RI-SMOM off-shell schemes. These schemes eliminate the need to model and subtract non-perturbative pion poles that arises in the RI-MOM scheme and, since the calculations are performed with domain wall fermions, the unphysical mixing between chirality sectors is suppressed. Our results for the bag parameters in the $\overline{\mathrm{MS}}$ scheme at $3\,\mathrm{GeV}$ are $B_K~\equiv~\mathcal{B}_1 = 0.5240(17)(54)$, $\mathcal{B}_2 = 0.4794(25)(35)$, $\mathcal{B}_3 = 0.746(13)(17)$, $\mathcal{B}_4 = 0.897(02)(10)$ and $\mathcal{B}_5 = 0.6882(78)(94)$, where the first error is from lattice uncertainties and the second is the uncertainty due to the perturbative matching to $\overline{\mathrm{MS}}$.Comment: 31 pages, 18 figures, 21 tables, 2 ancillary file

The specification, acceptability and effectiveness of respite care and short breaks for young adults with complex healthcare needs: protocol for a mixed-methods systematic review

IntroductionThe number of young adults with complex healthcare needs due to life-limiting conditions/complex physical disability has risen significantly as children with complex conditions survive into adulthood. Respite care and short breaks are an essential service, however, needs often go unmet after the transition to adult services, leading to a significant impact on the life expectancy and quality of life for this population. We aim to identify, appraise and synthesise relevant evidence to explore respite care and short breaks provision for this population, and to develop a conceptual framework for understanding service models.Methods and analysisA mixed-methods systematic review conducted in two stages: (1) knowledge map and (2) evidence review. We will comprehensively search multiple electronic databases; use the Citations, Lead authors, Unpublished materials, Google Scholar, Theories, Early examples, and Related projects (CLUSTER) approach, search relevant websites and circulate a ‘call for evidence’. Using the setting, perspective, intervention/phenomenon of interest, comparison and evaluation framework, two reviewers will independently select evidence for inclusion into a knowledge map and subsequent evidence review, extract data relating to study and population characteristics, methods and outcomes; and assess the quality of evidence. A third reviewer will arbitrate where necessary.Evidence will be synthesised using the following approaches: quantitative (narratively/conducting meta-analyses where appropriate); qualitative (framework approach); policy and guidelines (documentary analysis informed approach). An overall, integrated synthesis will be created using a modified framework approach. We will use Grading of Recommendations Assessment, Development and Evaluation (GRADE)/GRADE-Confidence in the Evidence from Reviews of Qualitative Research to assess the strength and confidence of the synthesised evidence. Throughout, we will develop a conceptual framework to articulate how service models work in relation to context and setting.Ethics and disseminationEthical approval is not required as this is a systematic review. We will present our work in academic journals, at appropriate conferences; we will disseminate findings across networks using a range of media. Steering and advisory groups were established to ensure findings are shared widely and in accessible formats.PROSPERO registration numberCRD42018088780

Gut microbiota induce IGF-1 and promote bone formation and growth

New interventions are needed to improve bone health and reduce the risk for osteoporosis and fracture. Dysbiosis is increasingly linked to metabolic abnormalities, although the effect of the microbiota on skeletal health is poorly understood. Previous studies suggest microbiota are detrimental to bone by increasing resorption. In this report, we show that the gut resident microbiota promote bone formation, as well as resorption, with long-term exposure to microbiota resulting in net skeletal growth. Microbiota induce the hormone insulin-like growth factor 1 (IGF-1), which promotes bone growth and remodeling. Short-chain fatty acids (SCFAs), produced when microbiota ferment fiber, also induce IGF-1, suggesting a mechanism by which microbiota affect bone health. Manipulating the microbiome or its metabolites may afford opportunities to optimize bone health and growth

Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria

BACKGROUND & AIMS: To explore the hypothesis that selective immune responses to distinct components of the intestinal microflora induce intestinal inflammation, we characterized disease kinetics and bacterial antigen-specific T-cell responses in ex germ-free interleukin 10 -/- and wild-type control mice monoassociated with Enterococcus faecalis , Escherichia coli , or Pseudomonas fluorescens . METHODS: Colitis was measured by using blinded histological scores and spontaneous interleukin 12 secretion from colonic strip culture supernatants. Interferon gamma secretion was measured from mesenteric or caudal lymph node CD4 + T cells stimulated with bacterial lysate-pulsed antigen-presenting cells. Luminal bacterial concentrations were measured by culture and quantitative polymerase chain reaction. RESULTS: Escherichia coli induced mild cecal inflammation after 3 weeks of monoassociation in interleukin 10 -/- mice. In contrast, Enterococcus faecalis-monoassociated interleukin 10 -/- mice developed distal colitis at 10-12 weeks that was progressively more severe and associated with duodenal inflammation and obstruction by 30 weeks. Neither bacterial strain induced inflammation in wild-type mice, and germ-free and Pseudomonas fluorescens-monoassociated interleukin 10 -/- mice remained disease free. CD4 + T cells from Enterococcus faecalis- or Escherichia coli-monoassociated interleukin 10 -/- mice selectively produced higher levels of interferon gamma and interleukin 4 when stimulated with antigen-presenting cells pulsed with the bacterial species that induced disease; these immune responses preceded the onset of histological inflammation in Enterococcus faecalis -monoassociated mice. Luminal bacterial concentrations did not explain regional differences in inflammation. CONCLUSIONS: Different commensal bacterial species selectively initiate immune-mediated intestinal inflammation with distinctly different kinetics and anatomic distribution in the same host

The epigenetic effects of a high prenatal folate intake in male mouse fetuses exposed in utero to arsenic

Inorganic arsenic (iAs) is a complete transplacental carcinogen in mice. Previous studies have demonstrated that in utero exposure to iAs promotes cancer in adult mouse offspring, possibly acting through epigenetic mechanisms. Humans and rodents enzymatically convert iAs to its methylated metabolites. This reaction requires S-adenosylmethionine (SAM) as methyl group donor. SAM is also required for DNA methylation. Supplementation with folate, a major dietary source of methyl groups for SAM synthesis, has been shown to modify iAs metabolism and the adverse effects of iAs exposure. However, effects of gestational folate supplementation on iAs metabolism and fetal DNA methylation have never been thoroughly examined. In the present study, pregnant CD1 mice were fed control (i.e. normal folate, or 2.2 mg/kg) or high folate diet (11 mg/kg) from gestational day (GD) 5 to 18 and drank water with 0 or 85 ppm of As (as arsenite) from GD8 to 18. The exposure to iAs significantly decreased body weight of GD18 fetuses and increased both SAM and S-adenosylhomocysteine (SAH) concentrations in fetal livers. High folate intake lowered the burden of total arsenic in maternal livers but did not prevent the effects of iAs exposure on fetal weight or hepatic SAM and SAH concentrations. In fact, combined folate-iAs exposure caused further significant body weight reduction. Notably, iAs exposure alone had little effect on DNA methylation in fetal livers. In contrast, the combined folate-iAs exposure changed the CpG island methylation in 2,931 genes, including genes known to be imprinted. Most of these genes were associated with neurodevelopment, cancer, cell cycle, and signaling networks. The canonical Wnt-signaling pathway, which regulates fetal development, was among the most affected biological pathways. Taken together, our results suggest that a combined in utero exposure to iAs and a high folate intake may adversely influence DNA methylation profiles and weight of fetuses, compromising fetal development and possibly increasing the risk for early-onset of disease in offspring

Navigating to new frontiers in behavioral neuroscience: traditional neuropsychological tests predict human performance on a rodent-inspired radial-arm maze

We constructed an 11-arm, walk-through, human radial-arm maze (HRAM) as a translational instrument to compare existing methodology in the areas of rodent and human learning and memory research. The HRAM, utilized here, serves as an intermediary test between the classic rat radial-arm maze (RAM) and standard human neuropsychological and cognitive tests. We show that the HRAM is a useful instrument to examine working memory ability, explore the relationships between rodent and human memory and cognition models, and evaluate factors that contribute to human navigational ability. One-hundred-and-fifty-seven participants were tested on the HRAM, and scores were compared to performance on a standard cognitive battery focused on episodic memory, working memory capacity, and visuospatial ability. We found that errors on the HRAM increased as working memory demand became elevated, similar to the pattern typically seen in rodents, and that for this task, performance appears similar to Miller's classic description of a processing-inclusive human working memory capacity of 7 ± 2 items. Regression analysis revealed that measures of working memory capacity and visuospatial ability accounted for a large proportion of variance in HRAM scores, while measures of episodic memory and general intelligence did not serve as significant predictors of HRAM performance. We present the HRAM as a novel instrument for measuring navigational behavior in humans, as is traditionally done in basic science studies evaluating rodent learning and memory, thus providing a useful tool to help connect and translate between human and rodent models of cognitive functioning

Recommendations for Epstein-Barr virus–based screening for nasopharyngeal cancer in high- and intermediate-risk regions

A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)–based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program