2,509 research outputs found
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Performing or not performing: what’s in a target?
This paper analyses how providers have coped with the 4-hour target over the past 7 years. To do this, we use publically available data from NHS digital to track how long patients remain in A&E departments and their “attendance disposal method.” Using this tool, we compared two A&E departments with similar arrival patterns and age profiles and that perform equally well against the target in a specific year. However, these hospitals exhibit very different underlying behaviour. Over 7 years, both exhibit a general increase in length of stay, increasing number of patients being admitted in the 20 minutes preceding the 4-hour target, and rising numbers of patients that breach the target. Despite the two hospitals having similar input profiles there is a 12 percentage point difference in the number of patients who leave the A&E department in the last 20 minutes. This operational information is not visible simply by monitoring the single existing metric. We conclude that the 4-hour target in isolation is an inadequate measure and we reflect on the difference between selecting measures for policy-level review, and for operational management. A link to download the graphs for each A&E in England is available
The lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes
Bergantin LB, Figueiredo LB, Godinho RO. the lumbrical muscle: a novel in situ system to evaluate adult skeletal muscle proteolysis and anticatabolic drugs for therapeutic purposes. J Appl Physiol 111: 1710-1718, 2011. First published September 15, 2011; doi:10.1152/japplphysiol.00586.2011.-The molecular regulation of skeletal muscle proteolysis and the pharmacological screening of anticatabolic drugs have been addressed by measuring tyrosine release from prepubertal rat skeletal muscles, which are thin enough to allow adequate in vitro diffusion of oxygen and substrates. However, the use of muscle at accelerated prepubertal growth has limited the analysis of adult muscle proteolysis or that associated with aging and neurodegenerative diseases. Here we established the adult rat lumbrical muscle (4/hindpaw; 8/rat) as a new in situ experimental model for dynamic measurement of skeletal muscle proteolysis. By incubating lumbrical muscles attached to their individual metatarsal bones in Tyrode solution, we showed that the muscle proteolysis rate of adult and aged rats (3-4 to 24 mo old) is 45-25% of that in prepubertal animals (1 mo old), which makes questionable the usual extrapolation of proteolysis from prepubertal to adult/senile muscles. While acute mechanical injury or 1- to 7-day denervation increased tyrosine release from adult lumbrical muscle by up to 60%, it was reduced by 20-28% after 2-h incubation with beta-adrenoceptor agonists, forskolin or phosphodiesterase inhibitor IBMX. Using inhibitors of 26S-proteasome (MG132), lysosome (methylamine), or calpain (E64/leupeptin) systems, we showed that ubiquitin-proteasome is accountable for 40-50% of total lumbrical proteolysis of adult, middle-aged, and aged rats. in conclusion, the lumbrical model allows the analysis of muscle proteolysis rate from prepubertal to senile rats. By permitting eight simultaneous matched measurements per rat, the new model improves similar protocols performed in paired extensor digitorum longus (EDL) muscles from prepubertal rats, optimizing the pharmacological screening of drugs for anticatabolic purposes.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Div Cellular Pharmacol, Dept Pharmacol, Escola Paulista Med, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Div Cellular Pharmacol, Dept Pharmacol, Escola Paulista Med, BR-04044020 São Paulo, BrazilFAPESP: 05/59006-1FAPESP: 08/55988-2CNPq: 304602/2008-6Web of Scienc
Investigation of the impact of the NICE guidelines regarding antibiotic prophylaxis during invasive dental procedures on the incidence of infective endocarditis in England: an electronic health records study
Background
Infective endocarditis is an uncommon but serious infection, where evidence for giving antibiotic prophylaxis before invasive dental procedures is inconclusive. In England, antibiotic prophylaxis was offered routinely to patients at risk of infective endocarditis until March 2008, when new guidelines aimed at reducing unnecessary antibiotic use were issued. We investigated whether changes in infective endocarditis incidence could be detected using electronic health records, assessing the impact of inclusion criteria/statistical model choice on inferences about the timing/type of any change.
Methods
Using national data from Hospital Episode Statistics covering 1998–2017, we modelled trends in infective endocarditis incidence using three different sets of inclusion criteria plus a range of regression models, identifying the most likely date for a change in trends if evidence for one existed. We also modelled trends in the proportions of different organism groups identified during infection episodes, using secondary diagnosis codes and data from national laboratory records. Lastly, we applied non-parametric local smoothing to visually inspect any changes in trend around the guideline change date.
Results
Infective endocarditis incidence increased markedly over the study (22.2–41.3 per million population in 1998 to 42.0–67.7 in 2017 depending on inclusion criteria). The most likely dates for a change in incidence trends ranged from September 2001 (uncertainty interval August 2000–May 2003) to May 2015 (March 1999–January 2016), depending on inclusion criteria and statistical model used. For the proportion of infective endocarditis cases associated with streptococci, the most likely change points ranged from October 2008 (March 2006–April 2010) to August 2015 (September 2013–November 2015), with those associated with oral streptococci decreasing in proportion after the change point. Smoothed trends showed no notable changes in trend around the guideline date.
Conclusions
Infective endocarditis incidence has increased rapidly in England, though we did not detect any change in trends directly following the updated guidelines for antibiotic prophylaxis, either overall or in cases associated with oral streptococci. Estimates of when changes occurred were sensitive to inclusion criteria and statistical model choice, demonstrating the need for caution in interpreting single models when using large datasets. More research is needed to explore the factors behind this increase
A shadowing problem in the detection of overlapping communities: lifting the resolution limit through a cascading procedure
Community detection is the process of assigning nodes and links in
significant communities (e.g. clusters, function modules) and its development
has led to a better understanding of complex networks. When applied to sizable
networks, we argue that most detection algorithms correctly identify prominent
communities, but fail to do so across multiple scales. As a result, a
significant fraction of the network is left uncharted. We show that this
problem stems from larger or denser communities overshadowing smaller or
sparser ones, and that this effect accounts for most of the undetected
communities and unassigned links. We propose a generic cascading approach to
community detection that circumvents the problem. Using real and artificial
network datasets with three widely used community detection algorithms, we show
how a simple cascading procedure allows for the detection of the missing
communities. This work highlights a new detection limit of community structure,
and we hope that our approach can inspire better community detection
algorithms.Comment: 14 pages, 12 figures + supporting information (5 pages, 6 tables, 3
figures
Prioritization of fish communities with a view to conservation and restoration on a large scale European basin, the Loire (France)
The hierarchical organization of important sites for the conservation or the
restoration of fish communities is a great challenge for managers, especially because of
financial or time constraints. In this perspective, we developed a methodology, which is
easy to implement in different locations. Based on the fish assemblage characteristics of
the Loire basin (France), we created a synthetic conservation value index including the
rarity, the conservation status and the species origin. The relationship between this new
synthetic index and the Fish-Based Index allowed us to establish a classification protocol
of the sites along the Loire including fish assemblages to be restored or conserved. Sites
presenting disturbed fish assemblages, a low rarity index, few threatened species, and a
high proportion of non-native species were considered as important for the restoration of
fish biodiversity. These sites were found mainly in areas where the assemblages are
typical of the bream zone, e.g. with a higher number of eurytopic and limnophilic
species. On the contrary, important sites for conservation were defined as having an
important conservation potential (high RI, a lot of threatened species, and few nonnatives
fish species) and an undisturbed fish assemblage similar to the expected community
if habitats are undisturbed. Important sites for conservation were found in the
Loire basin’s medium reaches which host assemblages typical for the grayling and the
barbell zones, e.g. with a higher number of rheophilic species. The synthetic conservation value index could be adapted and completed with other criteria according to
management priorities and capacities
Examining a staging model for anorexia nervosa: empirical exploration of a four stage model of severity.
Background: An illness staging model for anorexia nervosa (AN) has received increasing attention, but assessing the merits of this concept is dependent on empirically examining a model in clinical samples. Building on preliminary findings regarding the reliability and validity of the Clinician Administered Staging Instrument for Anorexia Nervosa (CASIAN), the current study explores operationalising CASIAN severity scores into stages and assesses their relationship with other clinical features. Method: In women with DSM-IV-R AN and sub-threshold AN (all met AN criteria using DSM 5), receiver operating curve (ROC) analysis (n = 67) assessed the relationship between the sensitivity and specificity of each stage of the CASIAN. Thereafter chi-square and post-hoc adjusted residual analysis provided a preliminary assessment of the validity of the stages comparing the relationship between stage and treatment intensity and AN sub-types, and explored movement between stages after six months (Time 3) in a larger cohort (n = 171). Results: The CASIAN significantly distinguished between milder stages of illness (Stage 1 and 2) versus more severe stages of illness (Stages 3 and 4), and approached statistical significance in distinguishing each of the four stages from one other. CASIAN Stages were significantly associated with treatment modality and primary diagnosis, and CASIAN Stage at Time 1 was significantly associated with Stage at 6 month follow-up. Conclusions: Provisional support is provided for a staging model in AN. Larger studies with longer follow-up of cases are now needed to replicate and extend these findings and evaluate the overall utility of staging as well as optimal staging models
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Investigating the impact of poverty on colonization and infection with drug-resistant organisms in humans: a systematic review
Background
Poverty increases the risk of contracting infectious diseases and therefore exposure to antibiotics. Yet there is lacking evidence on the relationship between income and non-income dimensions of poverty and antimicrobial resistance. Investigating such relationship would strengthen antimicrobial stewardship interventions.
Methods
A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Ovid, MEDLINE, EMBASE, Scopus, CINAHL, PsychINFO, EBSCO, HMIC, and Web of Science databases were searched in October 2016. Prospective and retrospective studies reporting on income or non-income dimensions of poverty and their influence on colonisation or infection with antimicrobial-resistant organisms were retrieved. Study quality was assessed with the Integrated quality criteria for review of multiple study designs (ICROMS) tool.
Results
Nineteen articles were reviewed. Crowding and homelessness were associated with antimicrobial resistance in community and hospital patients. In high-income countries, low income was associated with Streptococcus pneumoniae and Acinetobacter baumannii resistance and a seven-fold higher infection rate. In low-income countries the findings on this relation were contradictory. Lack of education was linked to resistant S. pneumoniae and Escherichia coli. Two papers explored the relation between water and sanitation and antimicrobial resistance in low-income settings.
Conclusions
Despite methodological limitations, the results suggest that addressing social determinants of poverty worldwide remains a crucial yet neglected step towards preventing antimicrobial resistance
Synchronous and Non-Synchronous Semelparity in Sibling Species of Pulmonates
Diverse life histories have been documented in terrestrial pulmonates, which inhabit different regions in climate. Life history traits are often phenotypically plastic and vary depending on the environment. Thus, surveys using designs that control for the confounding effects of environment are needed to evaluate the evolutionary differences between populations of closely related species in the wild. We examined the life histories of sibling species of terrestrial pulmonate within two regions of similar climates. Bradybaena pellucida (BP) is endemic to Japanese islands, and has recently been expanding its distribution northeastward, whereas B. similaris (BS) has been introduced by humans into temperate and tropical regions worldwide. We found that these species exhibit discrete differences in population dynamics and life cycle, despite their close relatedness. The annual life cycle of BP is synchronized among individuals in a population. Thus, BP is univoltine with discontinuous generation. In contrast, BS individuals do not synchronize their growth or reproduction, and thus exhibit overlapping generations. Our results indicate that synchronized and non-synchronized population dynamics diverge relatively rapidly in semelparous pulmonates. This type of difference has not been documented in pulmonate life history, and may have been overlooked because only a few studies have explicitly compared life cycles of closely related species within the same climate. Our results provide a basis for further studies of life history evolution in pulmonates.ArticleZOOLOGICAL SCIENCE. 32(4):372-377 (2015)journal articl
Creatine-induced activation of antioxidative defence in myotube cultures revealed by explorative NMR-based metabonomics and proteomics
<p>Abstract</p> <p>Background</p> <p>Creatine is a key intermediate in energy metabolism and supplementation of creatine has been used for increasing muscle mass, strength and endurance. Creatine supplementation has also been reported to trigger the skeletal muscle expression of insulin like growth factor I, to increase the fat-free mass and improve cognition in elderly, and more explorative approaches like transcriptomics has revealed additional information. The aim of the present study was to reveal additional insight into the biochemical effects of creatine supplementation at the protein and metabolite level by integrating the explorative techniques, proteomics and NMR metabonomics, in a systems biology approach.</p> <p>Methods</p> <p>Differentiated mouse myotube cultures (C2C12) were exposed to 5 mM creatine monohydrate (CMH) for 24 hours. For proteomics studies, lysed myotubes were analyzed in single 2-DGE gels where the first dimension of protein separation was pI 5-8 and second dimension was a 12.5% Criterion gel. Differentially expressed protein spots of significance were excised from the gel, desalted and identified by peptide mass fingerprinting using MALDI-TOF MS. For NMR metabonomic studies, chloroform/methanol extractions of the myotubes were subjected to one-dimensional <sup>1</sup>H NMR spectroscopy and the intracellular oxidative status of myotubes was assessed by intracellular DCFH<sub>2 </sub>oxidation after 24 h pre-incubation with CMH.</p> <p>Results</p> <p>The identified differentially expressed proteins included vimentin, malate dehydrogenase, peroxiredoxin, thioredoxin dependent peroxide reductase, and 75 kDa and 78 kDa glucose regulated protein precursors. After CMH exposure, up-regulated proteomic spots correlated positively with the NMR signals from creatine, while down-regulated proteomic spots were negatively correlated with these NMR signals. The identified differentially regulated proteins were related to energy metabolism, glucose regulated stress, cellular structure and the antioxidative defence system. The suggested improvement of the antioxidative defence was confirmed by a reduced intracellular DCFH<sub>2 </sub>oxidation with increasing concentrations of CMH in the 24 h pre-incubation medium.</p> <p>Conclusions</p> <p>The explorative approach of this study combined with the determination of a decreased intracellular DCFH<sub>2 </sub>oxidation revealed an additional stimulation of cellular antioxidative mechanisms when myotubes were exposed to CMH. This may contribute to an increased exercise performance mediated by increased ability to cope with training-induced increases in oxidative stress.</p
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