Absorbent products for urinary/faecal incontinence: a comparative evaluation of key product designs

Background: The UK health service, nursing homes and public spend around £94 million per year on incontinence pads (absorbent products) to contain urine and/or faeces, but the research base for making informed choices between different product designs is very weak.Objectives: The aim of this trial was to compare the performance and cost-effectiveness of the key absorbent product designs to provide a more solid basis for guiding selection and purchase.A further aim was to carry out the first stage in the development of a quality of life instrument for measuring the impact of absorbent product use on users' lives.Design: The work involved three clinical trials focusing on the three biggest market sectors. Each trial had a similar crossover design in which each participant tested all products within their group in random order.Settings, participants and methods: In Trial 1, 85 women with light urinary incontinence living in the community tested three products from each of the four design categories available (total of 12 test products): disposable inserts (pads); menstrual pads; washable pants with integral pad; and washable inserts. In Trial 2a, 85 moderate/heavily incontinent adults (urinary or urinary/faecal) living in the community (49 men and 36 women) tested three (or two) products from each of the five design categories available (total of 14 test products): disposable inserts (with mesh pants); disposable diapers (nappies); disposable pull-ups (similar to toddlers' trainer pants); disposable T-shaped diapers (nappies with waist-band); and washable diapers. All products were provided in a daytime and a (mostly more absorbent) night-time variant. In these first two trials, the test products were selected on the basis of data from pilot studies. In Trial 2b, 100 moderate/heavily incontinent adults (urinary or urinary/faecal) living in 10 nursing homes (27 men and 73 women) evaluated one product from each of the four disposable design categories from Trial 2a. Products were selected on the basis of product performance in Trial 2a and, again, daytime and night-time variants were provided. The first phase of work to develop a quality of life tool for measuring the impact of using different pad designs was carried out by interviewing participants from Trials 1 and 2a.Outcome measures: Product performance was characterised using validated questionnaires, which asked the participants (in Trials 1 and 2a) or carers (all participants in Trial 2b, except for the few who could report for themselves) to evaluate various aspects of pad performance (leakage, ease of putting on, discreetness, etc.) using a five-point scale (very good–very poor) at the end of the week (or 2 weeks for Trial 2b) of product testing. In addition, participants/carers were asked to save individual used pads in bags for weighing and to indicate the severity of any leakage from them on a three-point scale (none, a little, a lot). These data were used to determine differences in leakage performance. Numbers of laundry items and pads used were recorded to estimate costs, and skin health changes were recorded by the participant or by the researchers (Trial 2b). At the end of testing, participants were interviewed and ranked their preferences (with and without costs), stated the acceptability of each design (highly acceptable–totally unacceptable) and recorded their overall opinion on a visual analogue scale (VAS) of 0–100 points (worst design–best design). This VAS score was used with product costs to estimate cost-effectiveness. In addition, a timed pad changing exercise was conducted with 10 women from Trial 2b to determine any differences between product designs.Results: Results presented are for statistically and clinically significant findings.<br/

Preterm infants harbour diverse Klebsiella populations, including atypical species that encode and produce an array of antimicrobial resistance- and virulence-associated factors

Klebsiella spp. are frequently enriched in the gut microbiota of preterm neonates, and overgrowth is associated with necrotizing enterocolitis (NEC), nosocomial infections and late-onset sepsis. Little is known about the genomic and phenotypic characteristics of preterm-associated Klebsiella as previous studies have focussed on recovery of antimicrobial-resistant isolates or culture independent molecular analyses. The aim of this study was to better characterize preterm-associated Klebsiella populations using phenotypic and genotypic approaches. Faecal samples from a UK cohort of healthy and sick preterm neonates (n=109) were screened on MacConkey agar to isolate lactose positive Enterobacteriaceae. Whole-genome sequences were generated for Klebsiella spp., and virulence and antimicrobial resistance genes identified. Antibiotic susceptibility profiling, and in vitro macrophage and iron assays were undertaken for the Klebsiella strains. Metapangenome analyses with a manually curated genome dataset were undertaken to examine diversity of Klebsiella oxytoca and related bacteria in a publicly available shotgun metagenome dataset. Approximately one-tenth of faecal samples harboured Klebsiella spp. (Klebsiella pneumoniae, 7.3 %; Klebsiella quasipneumoniae, 0.9 %; Klebsiella grimontii, 2.8 %; Klebsiella michiganensis, 1.8 %). Isolates recovered from NEC- and sepsis-affected infants and those showing no signs of clinical infection (i.e. 'healthy') encoded multiple -lactamases. No difference was observed between isolates recovered from ‘healthy’ and sick infants with respect to in vitro siderophore production (all encoded enterobactin in their genomes). All K. pneumoniae, K. quasipneumoniae, K. grimontii and K. michiganensis faecal isolates tested were able to reside and persist in macrophages, indicating their immune evasion abilities. Metapangenome analyses of published metagenomic data confirmed our findings regarding the presence of K. michiganensis in the preterm gut. There is little difference in the phenotypic and genomic characteristics of Klebsiella isolates recovered from 'healthy' and sick infants. Identification of -lactamases in all isolates may prove problematic when defining treatment regimens for NEC or sepsis, and suggests ‘healthy’ preterm infants contribute to the resistome. Refined analyses with curated sequence databases are required when studying closely related species present in metagenomic data

Synthetic Observations of Simulated AGN Jets: X-ray Cavities

Observations of X-ray cavities formed by powerful jets from AGN in galaxy cluster cores are widely used to estimate the energy output of the AGN. Using methods commonly applied to observations of clusters, we conduct synthetic X-ray observations of 3D MHD simulated jet-ICM interactions to test the reliability of measuring X-ray cavity power. These measurements are derived from empirical estimates of the enthalpy content of the cavities and their implicit ages. We explore how such physical factors as jet intermittency and observational conditions such as orientation of the jets with respect to the line of sight impact the reliability of observational measurements of cavity enthalpy and age. An estimate of the errors in these quantities can be made by directly comparing "observationally" derived values with "actual" values from the simulations. In our tests, cavity enthalpy derived from observations was typically within a factor of two of the simulation values. Cavity age and, therefore, cavity power are sensitive to the accuracy of the estimated inclination angle of the jets. Cavity age and power estimates within a factor of two of the actual values are possible given an accurate inclination angle.Comment: 34 pages, 14 figures, accepted for publication in Ap

Moving from information and collaboration to action: report from the 3rd International Dog Health Workshop, Paris in April 2017

Abstract Background Breed-related health problems in dogs have received increased focus over the last decade. Responsibility for causing and/or solving these problems has been variously directed towards dog breeders and kennel clubs, the veterinary profession, welfare scientists, owners, regulators, insurance companies and the media. In reality, all these stakeholders are likely to share some responsibility and optimal progress on resolving these challenges requires all key stakeholders to work together. The International Partnership for Dogs (IPFD), together with an alternating host organization, holds biennial meetings called the International Dog Health Workshops (IDHW). The Société Centrale Canine (French Kennel Club) hosted the 3rd IDHW, in Paris, in April, 2017. These meetings bring together a wide range of stakeholders in dog health, science and welfare to improve international sharing of information and resources, to provide a forum for ongoing collaboration, and to identify specific needs and actions to improve health, well-being and welfare in dogs. Results The workshop included 140 participants from 23 countries and was structured around six important issues facing those who work to improve dog health. These included individualized breed-specific strategies for health and breeding, extreme conformations, education and communication in relation to antimicrobial resistance, behavior and welfare, genetic testing and population-based evidence. A number of exciting actions were agreed during the meeting. These included setting up working groups to create tools to help breed clubs accelerate the implementation of breed-health strategies, review aspects of extreme conformation and share useful information on behavior. The meeting also heralded the development of an online resource of relevant information describing quality measures for DNA testing. A demand for more and better data and evidence was a recurring message stressed across all themes. Conclusions The meeting confirmed the benefits from inclusion of a diverse range of stakeholders who all play relevant and collaborative parts to improve future canine health. Firm actions were set for progress towards improving breed-related welfare. The next international workshop will be in the UK in 2019 and will be organized by the UK Kennel Club

Space-time extensions II

The global extendibility of smooth causal geodesically incomplete spacetimes is investigated. Denote by $\gamma$ one of the incomplete non-extendible causal geodesics of a causal geodesically incomplete spacetime $(M,g_{ab})$. First, it is shown that it is always possible to select a synchronised family of causal geodesics $\Gamma$ and an open neighbourhood $\mathcal{U}$ of a final segment of $\gamma$ in $M$ such that $\mathcal{U}$ is comprised by members of $\Gamma$, and suitable local coordinates can be defined everywhere on $\mathcal{U}$ provided that $\gamma$ does not terminate either on a tidal force tensor singularity or on a topological singularity. It is also shown that if, in addition, the spacetime, $(M,g_{ab})$, is globally hyperbolic, and the components of the curvature tensor, and its covariant derivatives up to order $k-1$ are bounded on $\mathcal{U}$, and also the line integrals of the components of the $k^{th}$-order covariant derivatives are finite along the members of $\Gamma$---where all the components are meant to be registered with respect to a synchronised frame field on $\mathcal{U}$---then there exists a $C^{k-}$ extension $\Phi: (M,g_{ab}) \rightarrow (\widehat{M},\widehat{g}_{ab})$ so that for each $\bar\gamma\in\Gamma$, which is inextendible in $(M,g_{ab})$, the image, $\Phi\circ\bar\gamma$, is extendible in $(\widehat{M},\widehat{g}_{ab})$. Finally, it is also proved that whenever $\gamma$ does terminate on a topological singularity $(M,g_{ab})$ cannot be generic.Comment: 42 pages, no figures, small changes to match the published versio

Control and regulation of S‐Adenosylmethionine biosynthesis by the regulatory β subunit and quinolone‐based compounds

Methylation is an underpinning process of life and provides control for biological processes such as DNA synthesis, cell growth, and apoptosis. Methionine adenosyltransferases (MAT) produce the cellular methyl donor, S‐Adenosylmethionine (SAMe). Dysregulation of SAMe level is a relevant event in many diseases, including cancers such as hepatocellular carcinoma and colon cancer. In addition, mutation of Arg264 in MATα1 causes isolated persistent hypermethioninemia, which is characterized by low activity of the enzyme in liver and high level of plasma methionine. In mammals, MATα1/α2 and MATβV1/V2 are the catalytic and the major form of regulatory subunits, respectively. A gating loop comprising residues 113–131 is located beside the active site of catalytic subunits (MATα1/α2) and provides controlled access to the active site. Here, we provide evidence of how the gating loop facilitates the catalysis and define some of the key elements that control the catalytic efficiency. Mutation of several residues of MATα2 including Gln113, Ser114, and Arg264 lead to partial or total loss of enzymatic activity, demonstrating their critical role in catalysis. The enzymatic activity of the mutated enzymes is restored to varying degrees upon complex formation with MATβV1 or MATβV2, endorsing its role as an allosteric regulator of MATα2 in response to the levels of methionine or SAMe. Finally, the protein–protein interacting surface formed in MATα2:MATβ complexes is explored to demonstrate that several quinolone‐based compounds modulate the activity of MATα2 and its mutants, providing a rational for chemical design/intervention responsive to the level of SAMe in the cellular environment