Four patients with a history of acute exacerbations of COPD: implementing the CHEST/Canadian Thoracic Society guidelines for preventing exacerbations

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Prevention of delirium (POD) for older people in hospital: study protocol for a randomised controlled feasibility trial

Background: Delirium is the most frequent complication among older people following hospitalisation. Delirium may be prevented in about one-third of patients using a multicomponent intervention. However, in the United Kingdom, the National Health Service has no routine delirium prevention care systems. We have developed the Prevention of Delirium Programme, a multicomponent delirium prevention intervention and implementation process. We have successfully carried out a pilot study to test the feasibility and acceptability of implementation of the programme. We are now undertaking preliminary testing of the programme. Methods/Design: The Prevention of Delirium Study is a multicentre, cluster randomised feasibility study designed to explore the potential effectiveness and cost-effectiveness of the Prevention of Delirium Programme. Sixteen elderly care medicine and orthopaedic/trauma wards in eight National Health Service acute hospitals will be randomised to receive the Prevention of Delirium Programme or usual care. Patients will be eligible for the trial if they have been admitted to a participating ward and are aged 65 years or over. The primary objectives of the study are to provide a preliminary estimate of the effectiveness of the Prevention of Delirium Programme as measured by the incidence of new onset delirium, assess the variability of the incidence of new-onset delirium, estimate the intracluster correlation coefficient and likely cluster size, assess barriers to the delivery of the Prevention of Delirium Programme system of care, assess compliance with the Prevention of Delirium Programme system of care, estimate recruitment and follow-up rates, assess the degree of contamination due to between-ward staff movements, and investigate differences in financial costs and benefits between the Prevention of Delirium Programme system of care and standard practice. Secondary objectives are to investigate differences in the number, severity and length of delirium episodes (including persistent delirium); length of stay in hospital; inhospital mortality; destination at discharge; health-related quality of life and health resource use; physical and social independence; anxiety and depression; and patient experience. Discussion: This feasibility study will be used to gather data to inform the design of a future definitive randomised controlled trial. Trial registration: ISRCTN01187372. Registered 13 March 2014

Macrophage Subset Sensitivity to Endotoxin Tolerisation by Porphyromonas gingivalis

Macrophages (MΦs) determine oral mucosal responses; mediating tolerance to commensal microbes and food whilst maintaining the capacity to activate immune defences to pathogens. MΦ responses are determined by both differentiation and activation stimuli, giving rise to two distinct subsets; pro-inflammatory M1- and anti-inflammatory/regulatory M2- MΦs. M2-like subsets predominate tolerance induction whereas M1 MΦs predominate in inflammatory pathologies, mediating destructive inflammatory mechanisms, such as those in chronic P.gingivalis (PG) periodontal infection. MΦ responses can be suppressed to benefit either the host or the pathogen. Chronic stimulation by bacterial pathogen associated molecular patterns (PAMPs), such as LPS, is well established to induce tolerance. The aim of this study was to investigate the susceptibility of MΦ subsets to suppression by P. gingivalis. CD14hi and CD14lo M1- and M2-like MΦs were generated in vitro from the THP-1 monocyte cell line by differentiation with PMA and vitamin D3, respectively. MΦ subsets were pre-treated with heat-killed PG (HKPG) and PG-LPS prior to stimulation by bacterial PAMPs. Modulation of inflammation was measured by TNFα, IL-1β, IL-6, IL-10 ELISA and NFκB activation by reporter gene assay. HKPG and PG-LPS differentially suppress PAMP-induced TNFα, IL-6 and IL-10 but fail to suppress IL-1β expression in M1 and M2 MΦs. In addition, P.gingivalis suppressed NFκB activation in CD14lo and CD14hi M2 regulatory MΦs and CD14lo M1 MΦs whereas CD14hi M1 pro-inflammatory MΦs were refractory to suppression. In conclusion, P.gingivalis selectively tolerises regulatory M2 MΦs with little effect on pro-inflammatory CD14hi M1 MΦs; differential suppression facilitating immunopathology at the expense of immunity

Time spent with cats is never wasted: Lessons learned from feline acromegalic cardiomyopathy, a naturally occurring animal model of the human disease

<div><p>Background</p><p>In humans, acromegaly due to a pituitary somatotrophic adenoma is a recognized cause of increased left ventricular (LV) mass. Acromegalic cardiomyopathy is incompletely understood, and represents a major cause of morbidity and mortality. We describe the clinical, echocardiographic and histopathologic features of naturally occurring feline acromegalic cardiomyopathy, an emerging disease among domestic cats.</p><p>Methods</p><p>Cats with confirmed hypersomatotropism (IGF-1>1000ng/ml and pituitary mass; n = 67) were prospectively recruited, as were two control groups: diabetics (IGF-1<800ng/ml; n = 24) and healthy cats without known endocrinopathy or cardiovascular disease (n = 16). Echocardiography was performed in all cases, including after hypersomatotropism treatment where applicable. Additionally, tissue samples from deceased cats with hypersomatotropism, hypertrophic cardiomyopathy and age-matched controls (n = 21 each) were collected and systematically histopathologically reviewed and compared.</p><p>Results</p><p>By echocardiography, cats with hypersomatotropism had a greater maximum LV wall thickness (6.5mm, 4.1–10.1mm) than diabetic (5.9mm, 4.2–9.1mm; Mann Whitney, p<0.001) or control cats (5.2mm, 4.1–6.5mm; Mann Whitney, p<0.001). Left atrial diameter was also greater in cats with hypersomatotropism (16.6mm, 13.0–29.5mm) than in diabetic (15.4mm, 11.2–20.3mm; Mann Whitney, p<0.001) and control cats (14.0mm, 12.6–17.4mm; Mann Whitney, p<0.001). After hypophysectomy and normalization of IGF-1 concentration (n = 20), echocardiographic changes proved mostly reversible. As in humans, histopathology of the feline acromegalic heart was dominated by myocyte hypertrophy with interstitial fibrosis and minimal myofiber disarray.</p><p>Conclusions</p><p>These results demonstrate cats could be considered a naturally occurring model of acromegalic cardiomyopathy, and as such help elucidate mechanisms driving cardiovascular remodeling in this disease.</p></div

Image informatics strategies for deciphering neuronal network connectivity

Brain function relies on an intricate network of highly dynamic neuronal connections that rewires dramatically under the impulse of various external cues and pathological conditions. Among the neuronal structures that show morphologi- cal plasticity are neurites, synapses, dendritic spines and even nuclei. This structural remodelling is directly connected with functional changes such as intercellular com- munication and the associated calcium-bursting behaviour. In vitro cultured neu- ronal networks are valuable models for studying these morpho-functional changes. Owing to the automation and standardisation of both image acquisition and image analysis, it has become possible to extract statistically relevant readout from such networks. Here, we focus on the current state-of-the-art in image informatics that enables quantitative microscopic interrogation of neuronal networks. We describe the major correlates of neuronal connectivity and present workflows for analysing them. Finally, we provide an outlook on the challenges that remain to be addressed, and discuss how imaging algorithms can be extended beyond in vitro imaging studies

Single‐Column Model Simulations of Subtropical Marine Boundary‐Layer Cloud Transitions Under Weakening Inversions

Results are presented of the GASS/EUCLIPSE single‐column model intercomparison study on the subtropical marine low‐level cloud transition. A central goal is to establish the performance of state‐of‐the‐art boundary‐layer schemes for weather and climate models for this cloud regime, using large‐eddy simulations of the same scenes as a reference. A novelty is that the comparison covers four different cases instead of one, in order to broaden the covered parameter space. Three cases are situated in the North‐Eastern Pacific, while one reflects conditions in the North‐Eastern Atlantic. A set of variables is considered that reflects key aspects of the transition process, making use of simple metrics to establish the model performance. Using this method, some longstanding problems in low‐level cloud representation are identified. Considerable spread exists among models concerning the cloud amount, its vertical structure, and the associated impact on radiative transfer. The sign and amplitude of these biases differ somewhat per case, depending on how far the transition has progressed. After cloud breakup the ensemble median exhibits the well‐known “too few too bright” problem. The boundary‐layer deepening rate and its state of decoupling are both underestimated, while the representation of the thin capping cloud layer appears complicated by a lack of vertical resolution. Encouragingly, some models are successful in representing the full set of variables, in particular, the vertical structure and diurnal cycle of the cloud layer in transition. An intriguing result is that the median of the model ensemble performs best, inspiring a new approach in subgrid parameterization

Comparisons of high-risk cervical HPV infections in Caribbean and US populations

<p>Abstract</p> <p>Background</p> <p>Disparities in cervical cancer incidence and mortality rates exist among women of African ancestry (African-American, African-Caribbean and African). Persistent cervical infection with Human papillomavirus (HPV) is associated with cervical dysplasia and if untreated, could potentially progress to invasive cervical cancer. Very few studies have been conducted to examine the true prevalence of HPV infection in this population. Comparisons of cervical HPV infection and the type-specific distribution of HPV were performed between cancer-free Caribbean and US women.</p> <p>Results</p> <p>The Caribbean population consisted of 212 women from Tobago and 99 women from Jamaica. The US population tested, consisted of 82 women from Pittsburgh. The majority of the US subjects was Caucasian, 74% (61/82) while 12% (10/82) and 13% (11/82) were African-American or other ethnic groups, respectively. The age-adjusted prevalence of any HPV infection among women from Tobago was 35%, while for Jamaica, it was 81% (p < 0.0001). The age-adjusted prevalence of HPV infection for Caribbean subjects was not statistically significantly different from the US (any HPV: 47% vs. 39%, p > 0.1; high-risk HPVs: 27% vs. 25%, p > 0.1); no difference was observed between US-Blacks and Jamaicans (any HPV: 92% vs. 81%, p > 0.1; high-risk HPV: 50% vs. 53%, p > 0.1). However, US-Whites had a lower age-adjusted prevalence of HPV infections compared to Jamaican subjects (any HPV: 29% vs. 81%, p < 0.0001; high-risk HPV: 20% vs. 53%, p < 0.001). Subjects from Jamaica, Tobago, and US-Blacks had a higher proportion of high-risk HPV infections (Tobago: 20%, Jamaica: 58%, US-Blacks: 40%) compared to US-Whites (15%). Similar observations were made for the presence of infections with multiple high-risk HPV types (Tobago: 12%, Jamaica: 43%, US-Blacks: 30%, US-Whites: 8%). Although we observed similar prevalence of HPV16 infections among Caribbean and US-White women, there was a distinct distribution of high-risk HPV types when comparisons were made between the ethnic groups.</p> <p>Conclusion</p> <p>The higher prevalence of cervical HPV infections and multiple high-risk infections in Caribbean and US-Black women may contribute to the high incidence and prevalence of cervical cancer in these populations. Evaluation of a larger sample size is currently ongoing to confirm the distinct distribution of HPV types between ethnic groups.</p

Spatiotemporal scaling of North American continental interior wetlands: implications for shorebird conservation

Within interior North America, erratic weather patterns and heterogeneous wetland complexes cause wide spatio-temporal variation in the resources available to migrating shorebirds. Identifying the pattern-generating components of landscape-level resources and the scales at which shorebirds respond to these patterns will better facilitate conservation efforts for these species. We constructed descriptive models that identified weather variables associated with creating the spatio-temporal patterns of shorebird habitat in ten landscapes in north-central Oklahoma. We developed a metric capable of measuring the dynamic composition and configuration of shorebird habitat in the region and used field data to empirically estimate the spatial scale at which shorebirds respond to the amount and configuration of habitat. Precipitation, temperature, solar radiation and wind speed best explained the incidence of wetland habitat, but relationships varied among wetland types. Shorebird occurrence patterns were best explained by habitat density estimates at a 1.5 km scale. This model correctly classified 86 % of shorebird observations. At this scale, when habitat density was low, shorebirds occurred in 5 % of surveyed habitat patches but occurrence reached 60 % when habitat density was high. Our results suggest scale dependence in the habitat-use patterns of migratory shorebirds. We discuss potential implications of our results and how integrating this information into conservation efforts may improve conservation strategies and management practices

The risk factors for unexplained antepartum stillbirths in Scotland, 1994 to 2003

Objective: To determine the factors contributing to unexplained antepartum stillbirth in Scotland. Study Design: A 10-year birth database in Scotland was used to compare the unexplained antepartum stillbirth with other birth outcomes. The sample unit was a pregnant mother with a gestational age of 20 weeks and above and with a fetal birth weight of 200 g and above. Result: Maternal age of 35 years and above, lower deprivation category, inaccessible area of residence, maternal smoking, maternal height of <160 cm and gestational age of above 39 weeks were significantly associated with unexplained antepartum stillbirth. In multivariable analysis only maternal age (adjusted odds ratio (OR): 1.8, confidence interval (CI): 1.1 to 3.0, P=0.02), smoking during pregnancy (adjusted OR: 2.0, CI: 1.1 to 3.5, P=0.02), and maternal height (adjusted OR: 1.4, CI: 1.1 to 1.8, P=0.01), remain significant. Screening of pregnancies based on these three risk factors had 4.2% sensitivity and 99.4% specificity. The prevalence of stillbirth for this population was 0.2%. A positive predictive value of only 1.2% implies that only 1 in 83 women with these three risk factors will have antepartum stillbirth. The remaining 82 will suffer needless anxiety and potentially diagnostic procedures. Conclusion: Advanced maternal age, maternal smoking, and shorter maternal height were associated risk for unexplained antepartum stillbirth but screening based on these factors would be of limited value