COPD care delivery pathways in five European Union countries : mapping and health care professionals' perceptions

Background: COPD is among the leading causes of chronic morbidity and mortality in the European Union with an estimated annual economic burden of €25.1 billion. Various care pathways for COPD exist across Europe leading to different responses to similar problems. Determining these differences and the similarities may improve health and the functioning of health services. Objective: The aim of this study was to compare COPD patients’ care pathway in five European Union countries including England, Ireland, the Netherlands, Greece, and Germany and to explore health care professionals’ (HCPs) perceptions about the current pathways. Methods: HCPs were interviewed in two stages using a qualitative, semistructured email interview and a face-to-face semistructured interview. Results: Lack of communication among different health care providers managing COPD and comorbidities was a common feature of the studied care pathways. General practitioners/family doctors are responsible for liaising between different teams/services, except in Greece where this is done through pulmonologists. Ireland and the UK are the only countries with services for patients at home to shorten unnecessary hospital stay. HCPs emphasized lack of communication, limited resources, and poor patient engagement as issues in the current pathways. Furthermore, no specified role exists for pharmacists and informal carers. Conclusion: Service and professional integration between care settings using a unified system targeting COPD and comorbidities is a priority. Better communication between health care providers, establishing a clear role for informal carers, and enhancing patients’ engagement could optimize current care pathways resulting in a better integrated system

Arnol'd Tongues and Quantum Accelerator Modes

The stable periodic orbits of an area-preserving map on the 2-torus, which is formally a variant of the Standard Map, have been shown to explain the quantum accelerator modes that were discovered in experiments with laser-cooled atoms. We show that their parametric dependence exhibits Arnol'd-like tongues and perform a perturbative analysis of such structures. We thus explain the arithmetical organisation of the accelerator modes and discuss experimental implications thereof.Comment: 20 pages, 6 encapsulated postscript figure

Morphological Instabilities in a growing Yeast Colony: Experiment and Theory

We study the growth of colonies of the yeast Pichia membranaefaciens on agarose film. The growth conditions are controlled in a setup where nutrients are supplied through an agarose film suspended over a solution of nutrients. As the thickness of the agarose film is varied, the morphology of the front of the colony changes. The growth of the front is modeled by coupling it to a diffusive field of inhibitory metabolites. Qualitative agreement with experiments suggests that such a coupling is responsible for the observed instability of the front.Comment: RevTex, 4 pages and 3 figure

High pH microbial ecosystems in a newly discovered, ephemeral, serpentinizing fluid seep at YanartaÅŸ (Chimera), Turkey

Gas seeps emanating from ophiolites at Yanartaş (Chimaera), Turkey, have been documented for thousands of years. Active serpentinization produces hydrogen and a range of carbon gases that may provide fuel for life. Here we report a newly discovered, ephemeral fluid seep emanating from a small gas vent at Yanartaş. Fluids and biofilms were sampled at the source and points downstream. We describe site conditions, and provide microbiological data in the form of enrichment cultures, scanning electron microscopy (SEM), carbon and nitrogen isotopic composition of solids, and PCR screens of nitrogen cycle genes. Source fluids are pH 11.95, with a Ca:Mg of ~200, and sediments under the ignited gas seep measure 60°C. Collectively, these data suggest the fluid is the product of active serpentinization at depth. Source sediments are primarily calcite and alteration products (chlorite and montmorillonite). Downstream, biofilms are mixed with montmorillonite. SEM shows biofilms distributed homogeneously with carbonates. Organic carbon accounts for 60% of the total carbon at the source, decreasing downstream to <15% as inorganic carbon precipitates. δ13C ratios of the organic carbon fraction of solids are depleted (−25 to −28 ‰) relative to the carbonates (−11 to −20‰). We conclude that heterotrophic processes are dominant throughout the surface ecosystem, and carbon fixation may be key down channel. δ15N ratios ~ 3‰, and absence of nifH in extracted DNA suggest that nitrogen fixation is not occurring in sediments. However, the presence of narG and nirS at most locations and in enrichments indicates genomic potential for nitrate and nitrite reduction. This small seep with shallow run-off is likely ephemeral, but abundant preserved microterracettes in the outflow and the surrounding area suggest it has been present for some time. This site and others like it present an opportunity for investigations of preserved deep biosphere signatures, and subsurface-surface interactions

Developing Brain Vital Signs: Initial Framework for Monitoring Brain Function Changes Over Time

Clinical assessment of brain function relies heavily on indirect behavior-based tests. Unfortunately, behavior-based assessments are subjective and therefore susceptible to several confounding factors. Event-related brain potentials (ERPs), derived from electroencephalography (EEG), are often used to provide objective, physiological measures of brain function. Historically, ERPs have been characterized extensively within research settings, with limited but growing clinical applications. Over the past 20 years, we have developed clinical ERP applications for the evaluation of functional status following serious injury and/or disease. This work has identified an important gap: the need for a clinically accessible framework to evaluate ERP measures. Crucially, this enables baseline measures before brain dysfunction occurs, and might enable the routine collection of brain function metrics in the future much like blood pressure measures today. Here, we propose such a framework for extracting specific ERPs as potential “brain vital signs.” This framework enabled the translation/transformation of complex ERP data into accessible metrics of brain function for wider clinical utilization. To formalize the framework, three essential ERPs were selected as initial indicators: (1) the auditory N100 (Auditory sensation); (2) the auditory oddball P300 (Basic attention); and (3) the auditory speech processing N400 (Cognitive processing). First step validation was conducted on healthy younger and older adults (age range: 22–82 years). Results confirmed specific ERPs at the individual level (86.81–98.96%), verified predictable age-related differences (P300 latency delays in older adults, p < 0.05), and demonstrated successful linear transformation into the proposed brain vital sign (BVS) framework (basic attention latency sub-component of BVS framework reflects delays in older adults, p < 0.05). The findings represent an initial critical step in developing, extracting, and characterizing ERPs as vital signs, critical for subsequent evaluation of dysfunction in conditions like concussion and/or dementia

The Viscous Nonlinear Dynamics of Twist and Writhe

Exploiting the "natural" frame of space curves, we formulate an intrinsic dynamics of twisted elastic filaments in viscous fluids. A pair of coupled nonlinear equations describing the temporal evolution of the filament's complex curvature and twist density embodies the dynamic interplay of twist and writhe. These are used to illustrate a novel nonlinear phenomenon: ``geometric untwisting" of open filaments, whereby twisting strains relax through a transient writhing instability without performing axial rotation. This may explain certain experimentally observed motions of fibers of the bacterium B. subtilis [N.H. Mendelson, et al., J. Bacteriol. 177, 7060 (1995)].Comment: 9 pages, 4 figure

Exploring the nature and diversity of microorganisms in healthcare and educational settings

Many human populations spend approximately 90 % of their time indoors, yet relatively little is known about the microbial communities associated with indoor environments. This is despite knowledge that these microorganisms can contribute to adverse health effects, including the acquisition of healthcare-associated infections, which cause significant morbidity and mortality. The concept of the ‘indoor microbiome’ is relatively new and to date, few studies have been field-based, systematic and long-term. Hospitals in particular, are unique environments which have been shown to drive microbial evolutionary processes as they contain a different sub-set of the human population. The study of the hospital microbiome could have important implications for healthcare and infection control. This thesis explores a range of methods for investigating microorganisms in different indoor environments, including a classroom and outpatient’s waiting areas and wards in a hospital. Results show that the classroom is much more heavily contaminated in terms of total viable counts (TVCs) of bacteria recovered than the hospital environment. This was thought to be attributed to the absence of a strict cleaning regime in the classroom. High-touch items were less contaminated than other objects, likely due to them being obvious cleaning targets. Potential pathogens, including a number of Enterobacteriaceae were cultured from the classroom, outpatient’s waiting area and ward. Virus nucleic acid was recovered from an outpatient’s area, including norovirus and rotavirus RNA. Adenovirus DNA was frequently isolated throughout a 3 month screening protocol and there appeared to be evidence to suggest that a viral marker may be more appropriate than TVCs for identifying viral contamination. Human-associated bacteria were found to be dominant on a hospital ward over a 12 month longitudinal screening study and the presence of numerous bacterial taxa, which may be of concern in the context of paediatrics and immunodeficient patients, was also demonstrated

On the origin of spaces: morphometric foundations of urban form evolution

The modern discipline of urban morphology gives us a ground for the comparative analysis of cities, which increasingly includes specific quantitative elements. In this paper, we make a further step forward towards the definition of a general method for the classification of urban form. We draw from morphometrics and taxonomy in life sciences to propose such method, which we name ‘urban morphometrics’. We then test it on a unit of the urban landscape named ‘Sanctuary Area’ (SA), explored in 45 cities whose origins span four historic time periods: Historic (medieval), Industrial (19th century), New Towns (post-WWII, high-rise) and Sprawl (post-WWII, low-rise). We describe each SA through 207 physical dimensions and then use these to discover features that discriminate them among the four temporal groups. Nine dimensions emerge as sufficient to correctly classify 90% of the urban settings by their historic origins. These nine attributes largely identify an area's ‘visible identity’ as reflected by three characteristics: (1) block perimeterness, or the way buildings define the street-edge; (2) building coverage, or the way buildings cover the land and (3) regular plot coverage, or the extent to which blocks are made of plots that have main access from a street. Hierarchical cluster analysis utilising only the nine key variables nearly perfectly clusters each SA according to its historic origin; moreover, the resulting dendrogram shows, just after WWII, the first ‘bifurcation’ of urban history, with the emergence of the modern city as a new ‘species’ of urban form. With ‘urban morphometrics’ we hope to extend urban morphological research and contribute to understanding the way cities evolve

<i>In vitro - in vivo </i>relations for the parenteral liposomal formulation of Amphotericin B:A clinically relevant approach with PBPK modeling

In vitro release testing is a useful tool for the quality control of controlled release parenteral formulations, but in vitro release test conditions that reflect or are able to predict the in vivo performance are advantageous. Therefore, it is important to investigate the factors that could affect drug release from formulations and relate them to in vivo performance. In this study the effect of media composition including albumin presence, type of buffer and hydrodynamics on drug release were evaluated on a liposomal Amphotericin B formulation (Ambisome®). A physiologically based pharmacokinetic (PBPK) model was developed using plasma concentration profiles from healthy subjects, in order to investigate the impact of each variable from the in vitro release tests on the prediction of the in vivo performance. It was found that albumin presence was the most important factor for the release of Amphotericin B from Ambisome®; both hydrodynamics setups, coupled with the PBPK model, had comparable predictive ability for simulating in vivo plasma concentration profiles. The PBPK model was extrapolated to a hypothetical hypoalbuminaemic population and the Amphotericin B plasma concentration and its activity against fungal cells were simulated. Selected in vitro release tests for these controlled release parenteral formulations were able to predict the in vivo AmB exposure, and this PBPK driven approach to release test development could benefit development of such formulations.</p

Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases

Thiolutin is a disulfide-containing antibiotic and anti-angiogenic compound produced by Streptomyces. Its biological targets are not known. We show that reduced thiolutin is a zinc chelator that inhibits the JAB1/MPN/Mov34 (JAMM) domain–containing metalloprotease Rpn11, a deubiquitinating enzyme of the 19S proteasome. Thiolutin also inhibits the JAMM metalloproteases Csn5, the deneddylase of the COP9 signalosome; AMSH, which regulates ubiquitin-dependent sorting of cell-surface receptors; and BRCC36, a K63-specific deubiquitinase of the BRCC36-containing isopeptidase complex and the BRCA1–BRCA2-containing complex. We provide evidence that other dithiolopyrrolones also function as inhibitors of JAMM metalloproteases