Influence of the intestinal microbiota on disease susceptibility in kittens with experimentally-induced carriage of atypical enteropathogenic Escherichia coli

Typical enteropathogenic E. coli (tEPEC) carries the highest hazard of death in children with diarrhea and atypical EPEC (aEPEC) was recently identified as significantly associated with diarrheal mortality in kittens. In both children and kittens there is a significant association between aEPEC burden and diarrheal disease, however the infection can be found in individuals with and without diarrhea. It remains unclear to what extent, under what conditions, or by what mechanisms aEPEC serves as a primary pathogen in individuals with diarrhea. It seems likely that a combination of host and bacterial factors enable aEPEC to cause disease in some individuals and not in others. The purpose of this study was to determine the impact of aEPEC on intestinal function and diarrhea in kittens following experimentally-induced carriage and the influence of a disrupted intestinal microbiota on disease susceptibility. Results of this study identify aEPEC as a potential pathogen in kittens. In the absence of disruption to the intestinal microbiota, kittens are resistant to clinical signs of aEPEC carriage but demonstrate significant occult changes in intestinal absorption and permeability. Antibiotic-induced disruption of the intestinal microbiota prior to infection increases subsequent intestinal water loss as determined by % fecal wet weight. Enrichment of the intestinal microbiota with a commensal member of the feline mucosa-associated microbiota, Enterococcus hirae, ameliorated the effects of aEPEC experimental infection on intestinal function and water loss. These observations begin to unravel the mechanisms by which aEPEC infection may be able to exploit susceptible hosts.Peer reviewe

Reply to Fischer et al

We welcome the correspondence from Fischer and colleagues regarding our recent paper on vocal learning in chimpanzee food grunts [1]. Fischer et al. make two challenges to our paper's conclusions, which we address here

The archival discovery of a strong Lyman-α\alpha and [CII] emitter at z = 7.677

We report the archival discovery of Lyman-$\alpha$ emission from the bright ultraviolet galaxy Y002 at $z=7.677$, spectroscopically confirmed by its ionized carbon [CII] 158$\mu$m emission line. The Ly$\alpha$ line is spatially associated with the rest-frame UV stellar emission ($M_{\rm UV}$~-22, 2x brighter than $M^\star_{\rm UV}$) and it appears offset from the peak of the extended [CII] emission at the current ~1" spatial resolution. We derive an estimate of the unobscured SFR(UV)=$(22\pm1)\,M_\odot$ yr$^{-1}$ and set an upper limit of SFR(IR)$<15\,M_\odot$ yr$^{-1}$ from the far-infrared wavelength range, which globally place Y002 on the SFR(UV+IR)-L([CII]) correlation observed at lower redshifts. In terms of velocity, the peak of the Ly$\alpha$ emission is redshifted by $\Delta v$(Ly$\alpha$)~500 km s$^{-1}$ from the systemic redshift set by [CII] and a high-velocity tail extends to up to ~1000 km s$^{-1}$. The velocity offset is up to ~3.5x higher than the average estimate for similarly UV-bright emitters at z~6-7, which might suggest that we are witnessing the merging of two clumps. A combination of strong outflows and the possible presence of an extended ionized bubble surrounding Y002 would likely facilitate the escape of copious Ly$\alpha$ light, as indicated by the large equivalent width EW(Ly$\alpha$)=$24^{+5}_{-6}$ \r{A}. Assuming that [CII] traces the neutral hydrogen, we estimate a HI gas fraction of $M({\rm HI})/M_\star\gtrsim8$ for Y002 as a system and speculate that patches of high HI column densities could contribute to explain the observed spatial offsets between Ly$\alpha$ and [CII] emitting regions. The low dust content, implied by the non-detection of the far-infrared continuum emission at rest-frame ~160 $\mu$m, would be sufficient to absorb any potential Ly$\alpha$ photons produced within the [CII] clump as a result of large HI column densities.Comment: 10 pages, 4 figures. Accepted for publication in The Astrophysical Journal Letter

Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel

Group recommended a panel of mutations and variants that should be tested to determine carrier status within the CFTR gene as a part of population screening programs.1,2 This was initially done in response to the recommendations of an NIH CF Consensus Conference that CF carrier screening be consid-ered by all couples for use before conception or prenatally.3 At that time, the Working Group recognized limitations in our understanding of the population frequencies of several CF al-leles and proposed to review mutation distribution data after the first two years of the program. In 2002, as part of an ongo-ing effort to ensure that the cystic fibrosis carrier screening programs are current with respect to the scientific literature and other available data and practices, we initiated a second review of data on the distribution of mutations in different ethnic groups and we began to assess whether providers wer

Global no net loss of natural ecosystems

A global goal of no net loss of natural ecosystems or better has recently been proposed, but such a goal would require equitable translation to country-level contributions. Given the wide variation in ecosystem depletion, these could vary from net gain (for countries where restoration is needed), to managed net loss (in rare circumstances where natural ecosystems remain extensive and human development imperative is greatest). National contributions and international support for implementation also must consider non-area targets factors such as the capacity to conserve and the imperative for human development

Establishing a distributed national research infrastructure providing bioinformatics support to life science researchers in Australia

EMBL Australia Bioinformatics Resource (EMBL-ABR) is a developing national research infrastructure, providing bioinformatics resources and support to life science and biomedical researchers in Australia. EMBL-ABR comprises 10 geographically distrib- uted national nodes with one coordinating hub, with current funding provided through Bioplatforms Australia and the University of Melbourne for its initial 2-year development phase. The EMBL-ABR mission is to: (1) increase Australia’s capacity in bioinformatics and data sciences; (2) contribute to the development of training in bioinformatics skills; (3) showcase Australian data sets at an international level and (4) enable engagement in international programs. The activities of EMBL-ABR are focussed in six key areas, aligning with comparable international initiatives such as ELIXIR, CyVerse and NIH Commons. These key areas—Tools, Data, Standards, Platforms, Compute and Training—are described in this article

Non-randomised feasibility study testing a primary care intervention to promote engagement in an online health community for adults with troublesome asthma: protocol

Introduction: In the UK, approximately 4.3 million adults have asthma, with one-third experiencing poor asthma control, affecting their quality of life, and increasing their healthcare use. Interventions promoting emotional/behavioural self-management can improve asthma control and reduce comorbidities and mortality. Integration of online peer support into primary care services to foster self-management is a novel strategy. We aim to co-design and evaluate an intervention for primary care clinicians to promote engagement with an asthma online health community (OHC). Our protocol describes a ‘survey leading to a trial’ design as part of a mixed-methods, non-randomised feasibility study to test the feasibility and acceptability of the intervention. Methods and analysis: Adults on the asthma registers of six London general practices (~3000 patients) will be invited to an online survey, via text messages. The survey will collect data on attitudes towards seeking online peer support, asthma control, anxiety, depression, quality of life, information on the network of people providing support with asthma and demographics. Regression analyses of the survey data will identify correlates/predictors of attitudes/receptiveness towards online peer support. Patients with troublesome asthma, who (in the survey) expressed interest in online peer support, will be invited to receive the intervention, aiming to reach a recruitment target of 50 patients. Intervention will involve a one-off, face-to-face consultation with a practice clinician to introduce online peer support, sign patients up to an established asthma OHC, and encourage OHC engagement. Outcome measures will be collected at baseline and 3 months post intervention and analysed with primary care and OHC engagement data. Recruitment, intervention uptake, retention, collection of outcomes, and OHC engagement will be assessed. Interviews with clinicians and patients will explore experiences of the intervention. Ethics and dissemination: Ethical approval was obtained from a National Health Service Research Ethics Committee (reference: 22/NE/0182). Written consent will be obtained before intervention receipt and interview participation. Findings will be shared via dissemination to general practices, conference presentations and peer-reviewed publications. Trial registration number: NCT05829265

HIDDen: Hospice Inpatient Deep vein thrombosis Detection prospective longitudinal observational study to explore the prevalence, symptom burden and natural history of venous thromboembolism in people with advanced cancer

BACKGROUND: The prevalence of deep venous thrombosis in patients with advanced cancer is unconfirmed and it is unknown whether current international thromboprophylaxis guidance is applicable to this population. We aimed to determine prevalence and predictors of femoral deep vein thrombosis in patients admitted to specialist palliative care units (SPCUs). METHODS: We did this prospective longitudinal observational study in five SPCUs in England, Wales, and Northern Ireland (four hospices and one palliative care unit). Consecutive adults with cancer underwent bilateral femoral vein ultrasonography on admission and weekly until death or discharge for a maximum of 3 weeks. Data were collected on performance status, attributable symptoms, and variables known to be associated with venous thromboembolism. Patients with a short estimated prognosis (<5 days) were ineligible. The primary endpoint of the study was the prevalence of femoral deep vein thrombosis within 48 h of SPCU admission, analysed by intention to treat. This study is registered with the ISRCTN registry, number ISRCTN97567719. FINDINGS: Between June 20, 2016, and Oct 16, 2017, 343 participants were enrolled (mean age 68·2 years [SD 12·8; range 25-102]; 179 [52%] male; mean Australian-modified Karnofsky performance status 49 [SD 16·6; range 20-90]). Of 273 patients with evaluable scans, 92 (34%, 95% CI 28-40) had femoral deep vein thrombosis. Four participants with a scan showing no deep vein thrombosis on admission developed a deep vein thrombosis on repeat scanning over 21 days. Previous venous thromboembolism (p=0·014), being bedbound in the past 12 weeks for any reason (p=0·003), and lower limb oedema (p=0·009) independently predicted deep vein thrombosis. Serum albumin concentration (p=0·43), thromboprophylaxis (p=0·17), and survival (p=0·45) were unrelated to deep vein thrombosis. INTERPRETATION: About a third of patients with advanced cancer admitted to SPCUs had a femoral deep vein thrombosis. Deep vein thrombosis was not associated with thromboprophylaxis, survival, or symptoms other than leg oedema. These findings are consistent with venous thromboembolism being a manifestation of advanced disease rather than a cause of premature death. Thromboprophylaxis for SPCU inpatients with poor performance status seems to be of little benefit. FUNDING: National Institute for Health Research (Research for Patient Benefit programme)

Extreme damped Lyman-α\alpha absorption in young star-forming galaxies at z=9−11z=9-11

The onset of galaxy formation is thought to be initiated by the infall of neutral, pristine gas onto the first protogalactic halos. However, direct constraints on the abundance of neutral atomic hydrogen (HI) in galaxies have been difficult to obtain at early cosmic times. Here we present spectroscopic observations with JWST of three galaxies at redshifts $z=8.8 - 11.4$, about $400-600$ Myr after the Big Bang, that show strong damped Lyman-$\alpha$ absorption ($N_{\rm HI} > 10^{22}$ cm$^{-2}$) from HI in their local surroundings, an order of magnitude in excess of the Lyman-$\alpha$ absorption caused by the neutral intergalactic medium at these redshifts. Consequently, these early galaxies cannot be contributing significantly to reionization, at least at their current evolutionary stages. Simulations of galaxy formation show that such massive gas reservoirs surrounding young galaxies so early in the history of the universe is a signature of galaxy formation in progress.Comment: Submitte