Pathogenesis of feline enteric coronavirus infection.

Fifty-one specific pathogen-free (SPF) cats 10 weeks to 13 years of age were infected with a cat-to-cat fecal-oral passed strain of feline enteric coronavirus (FECV). Clinical signs ranged from unapparent to a mild and self-limiting diarrhea. Twenty-nine of these cats were FECV naïve before infection and followed sequentially for fecal virus shedding and antibody responses over a period of 8-48 months. Fecal shedding, as determined by real-time polymerase chain reaction (RT-PCR) from rectal swabs, appeared within a week and was significantly higher in kittens than older cats. FECV shedding remained at high levels for 2-10 months before eventually evolving into one of three excretion patterns. Eleven cats shed the virus persistently at varying levels over an observation period of 9-24 months. Eleven cats appeared to have periods of virus shedding interlaced with periods of non-shedding (intermittent or recurrent shedders), and seven cats ceased shedding after 5-19 months (average 12 months). There was no change in the patterns of virus shedding among cats that were excreting FECV at the time of a secondary challenge exposure. Four cats, which had ceased shedding, re-manifested a primary type infection when secondarily infected. Cats with higher feline coronavirus (FCoV) antibody titers were significantly more likely to shed virus, while cats with lower titers were significantly less likely to be shedding. Twenty-two kittens born to experimentally infected project queens began shedding virus spontaneously, but never before 9-10 weeks of age. Natural kittenhood infections appeared to be low grade and abortive. However, a characteristic primary type infection occurred following experimental infection with FECV at 12-15 weeks of age. Pregnancy, parturition and lactation had no influence on fecal shedding by queens. Methylprednisolone acetate treatment did not induce non-shedders to shed and shedders to increase shedding

The 21-SPONGE HI Absorption Survey I: Techniques and Initial Results

We present methods and results from "21-cm Spectral Line Observations of Neutral Gas with the EVLA" (21-SPONGE), a large survey for Galactic neutral hydrogen (HI) absorption with the Karl G. Jansky Very Large Array (VLA). With the upgraded capabilities of the VLA, we reach median root-mean-square (RMS) noise in optical depth of $\sigma_{\tau}=9\times 10^{-4}$ per $0.42\rm\,km\,s^{-1}$ channel for the 31 sources presented here. Upon completion, 21-SPONGE will be the largest HI absorption survey with this high sensitivity. We discuss the observations and data reduction strategies, as well as line fitting techniques. We prove that the VLA bandpass is stable enough to detect broad, shallow lines associated with warm HI, and show that bandpass observations can be combined in time to reduce spectral noise. In combination with matching HI emission profiles from the Arecibo Observatory ($\sim3.5'$ angular resolution), we estimate excitation (or spin) temperatures ($\rm T_s$) and column densities for Gaussian components fitted to sightlines along which we detect HI absorption (30/31). We measure temperatures up to $\rm T_s\sim1500\rm\,K$ for individual lines, showing that we can probe the thermally unstable interstellar medium (ISM) directly. However, we detect fewer of these thermally unstable components than expected from previous observational studies. We probe a wide range in column density between $\sim10^{16}$ and $>10^{21}\rm\,cm^{-2}$ for individual HI clouds. In addition, we reproduce the trend between cold gas fraction and average $\rm T_s$ found by synthetic observations of a hydrodynamic ISM simulation by Kim et al. (2014). Finally, we investigate methods for estimating HI $\rm T_s$ and discuss their biases.Comment: Accepted for publication in ApJ; 24 pages, 14 figure

The BRACELET Study: surveys of mortality in UK neonatal and paediatric intensive care trials.

BACKGROUND: The subject of death and bereavement in the context of randomised controlled trials in neonatal or paediatric intensive care is under-researched. The objectives of this phase of the Bereavement and RAndomised ControlLEd Trials (BRACELET) Study were to determine trial activity in UK neonatal and paediatric intensive care (2002-06); numbers of deaths before hospital discharge; and variation in mortality across intensive care units and trials and to determine whether bereavement support policies were available within trials. These are essential prerequisites to considering the implications of future policies and practice subsequent to bereavement following a child's enrollment in a trial. METHODS: The units survey involved neonatal units providing level 2 or 3 care, and paediatric units providing level II care or above; the trials survey involved trials where allocation was randomized and interventions were delivered to intensive care patients, or to parents but designed to affect patient outcomes. RESULTS: Information was available from 191/220 (87%) neonatal units (149 level 2 or 3 care); and 28/32 (88%) paediatric units. 90/177 (51%) eligible responding units participated in one or more trial (76 neonatal, 14 paediatric) and 54 neonatal units and 6 paediatric units witnessed at least one death. 50 trials were identified (36 neonatal, 14 paediatric). 3,137 babies were enrolled in neonatal trials, 210 children in paediatric trials. Deaths ranged 0-278 (median [IQR interquartile range] 2 [1, 14.5]) per neonatal trial, 0-4 (median [IQR] 1 [0, 2.5]) per paediatric trial. 534 (16%) participants died post-enrollment: 522 (17%) in neonatal trials, 12 (6%) in paediatric trials. Trial participants ranged 1-236 (median [IQR] 21.5 [8, 39.8]) per neonatal unit, 1-53 (median [IQR] 11.5 [2.3, 33.8]) per paediatric unit. Deaths ranged 0-37 (median [IQR] 3.5 [0.3, 8.8]) per neonatal unit, 0-7 (median [IQR] 0.5 [0, 1.8]) per paediatric unit. Three trials had a formal policy for responding to bereavement. CONCLUSIONS: A substantial number of deaths after trial enrollment were identified, distributed over many trials and units. Few trial teams had responses to bereavement in place. Those with the largest numbers of deaths might be best placed to collaborate in developing and assessing responses to bereavement.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Dogs are more permissive than cats or guinea pigs to experimental infection with a human isolate of Bartonella rochalimae

Bartonella rochalimae was first isolated from the blood of a human who traveled to Peru and was exposed to multiple insect bites. Foxes and dogs are likely natural reservoirs for this bacterium. We report the results of experimental inoculation of two dogs, five cats and six guinea pigs with the only human isolate of this new Bartonella species. Both dogs became bacteremic for 5–7 weeks, with a peak of 103–104 colony forming units (CFU)/mL blood. Three cats had low bacteremia levels (< 200 CFU/mL) of 6–8 weeks’ duration. One cat that remained seronegative had two bacterial colonies isolated at a single culture time point. A fifth cat never became bacteremic, but seroconverted. None of the guinea pigs became bacteremic, but five seroconverted. These results suggest that dogs could be a reservoir of this strain of B. rochalimae, in contrast to cats and guinea pigs

Utility of ultrasound in the assessment of swallowing and laryngeal function: A rapid review and critical appraisal of the literature

BACKGROUND: Ultrasound (US) is not widely used as part of the speech and language therapy (SLT) clinical toolkit. The COVID-19 pandemic has intensified interest in US as an alternative to SLT instrumental tools such as the videofluoroscopic swallowing study (VFSS), fibreoptic endoscopic evaluation of swallowing (FEES) and endoscopic evaluation of the larynx (EEL) as a non-invasive, non-aerosol-generating procedure that can be delivered at the bedside to assess swallowing and/or laryngeal function. To establish the appropriacy of routine US use, and in response to a national professional body request for a position statement, a group of expert SLTs conducted a rapid review of the literature. AIM: To explore critically the clinical utility of US as an assessment tool for swallowing and laryngeal function in adults. METHODS & PROCEDURES: A rapid review of four databases was completed to identify articles using US to assess swallowing and/or laryngeal function in adults compared with reference tests (VFSS/FEES/EEL/validated outcome measure). Screening was completed according to predefined inclusion/exclusion criteria and 10% of abstracts were rescreened to assess reliability. Data were extracted from full texts using a predeveloped form. The QUADAS-2 tool was used for quality ratings. Information from included studies was summarized using narrative synthesis and visual illustration. OUTCOMES & RESULTS: Ten papers used US to assess swallowing, and 13 to assess laryngeal function. All were peer-reviewed primary studies across a range of clinical populations and with a wide geographical spread. Four papers had an overall low risk of bias, but the remaining 19 had at least one domain where risk of bias was judged as high or unclear. Applicability concerns were identified in all papers. The papers that used US to assess swallowing varied widely in terms of the anatomical structures assessed and methodology employed. The papers assessing laryngeal function were more homogenous in their methodology. Sensitivity and specificity data were provided for 12 of the laryngeal function papers with ranges of 64.3–100% and 48.5–100%, respectively. CONCLUSIONS & IMPLICATIONS: There is burgeoning evidence to support the use of US as an adjunct to SLT clinical assessment of swallowing and laryngeal function. However, the current literature does not support its use as a tool in isolation. Further research is required to establish reliability in US assessment as well as clear SLT-driven protocols and training

Considerations for defining+80 Da mass shifts in mass spectrometry-based proteomics: phosphorylation and beyond

Post-translational modifications (PTMs) are ubiquitous and key to regulating protein function. Understanding the dynamics of individual PTMs and their biological roles requires robust characterisation. Mass spectrometry (MS) is the method of choice for the identification and quantification of protein modifications. This article focusses on the MS-based analysis of those covalent modifications that induce a mass shift of +80 Da, notably phosphorylation and sulfation, given the challenges associated with their discrimination and pinpointing the sites of modification on a polypeptide chain. Phosphorylation in particular is highly abundant, dynamic and can occur on numerous residues to invoke specific functions, hence robust characterisation is crucial to understanding biological relevance. Showcasing our work in the context of other developments in the field, we highlight approaches for enrichment and site localisation of phosphorylated (canonical and non-canonical) and sulfated peptides, as well as modification analysis in the context of intact proteins (top down proteomics) to explore combinatorial roles. Finally, we discuss the application of native ion-mobility MS to explore the effect of these PTMs on protein structure and ligand binding

Servants and masters: an activity theory investigation of human-AI roles in the performance of work

Organizations considering AI adoption must be mindful of media that portrays dystopian future scenarios. While machine sentience remains philosophically and ethically moot, the future implications of AI adoption are unclear. The issues that surround AI adoption need to be examined but there are a lack of implementations cases around which empirical research can be undertaken and practical experience can be gained. AI adoption needs to be considered from multiple viewpoints including, but not necessarily limited to the social, ethical and legal issues, and not merely be reduced to questions of financial return or organizational efficiency