Method for Quantitative Study of Airway Functional Microanatomy Using Micro-Optical Coherence Tomography

We demonstrate the use of a high resolution form of optical coherence tomography, termed micro-OCT (μOCT), for investigating the functional microanatomy of airway epithelia. μOCT captures several key parameters governing the function of the airway surface (airway surface liquid depth, periciliary liquid depth, ciliary function including beat frequency, and mucociliary transport rate) from the same series of images and without exogenous particles or labels, enabling non-invasive study of dynamic phenomena. Additionally, the high resolution of μOCT reveals distinguishable phases of the ciliary stroke pattern and glandular extrusion. Images and functional measurements from primary human bronchial epithelial cell cultures and excised tissue are presented and compared with measurements using existing gold standard methods. Active secretion from mucus glands in tissue, a key parameter of epithelial function, was also observed and quantified

The implications of climate change for the water environment in England

This paper reviews the implications of climate change for the water environment and its management in England. There is a large literature, but most studies have looked at flow volumes or nutrients and none have considered explicitly the implications of climate change for the delivery of water management objectives. Studies have been undertaken in a small number of locations. Studies have used observations from the past to infer future changes, and have used numerical simulation models with climate change scenarios. The literature indicates that climate change poses risks to the delivery of water management objectives, but that these risks depend on local catchment and water body conditions. Climate change affects the status of water bodies, and it affects the effectiveness of measures to manage the water environment and meet policy objectives. The future impact of climate change on the water environment and its management is uncertain. Impacts are dependent on changes in the duration of dry spells and frequency of ‘flushing’ events, which are highly uncertain and not included in current climate scenarios. There is a good qualitative understanding of ways in which systems may change, but interactions between components of the water environment are poorly understood. Predictive models are only available for some components, and model parametric and structural uncertainty has not been evaluated. The impacts of climate change depend on other pressures on the water environment in a catchment, and also on the management interventions that are undertaken to achieve water management objectives. The paper has also developed a series of consistent conceptual models describing the implications of climate change for pressures on the water environment, based around the source-pathway-receptor concept. They provide a framework for a systematic assessment across catchments and pressures of the implications of climate change for the water environment and its management

A Novel, Single Algorithm Approach to Predict Acenocoumarol Dose Based on CYP2C9 and VKORC1 Allele Variants

The identification of CYP2C9 and VKORC1 genes has strongly stimulated the research on pharmacogenetics of coumarins in the last decade. We assessed the combined influence of CYP2C9 *2 and *3, and VKORC1 c.-1639G>A, 497C>G, and 1173C>T variants, on acenocoumarol dosage using a novel algorithm approach, in 193 outpatients who had achieved stable anticoagulation. We constructed an “acenocoumarol-dose genotype score” (AGS, maximum score = 100) based on the number of alleles associated with higher acenocoumarol dosage carried by each subject for each polymorphism. The mean AGS was higher in the high-dose (>28mg/week) compared with the low-dose (<7mg/week) group (mean(SEM) of 84.1±3.4 vs. 62.2±4.8, P = 0.008). An AGS>70 was associated with an increased odds ratio (OR) of requiring high acenocoumarol dosage (OR: 3.347; 95%CI: 1.112–10.075; P = 0.032). In summary, although more research is necessary in other patient cohorts, and this algorithm should be replicated in an independent sample, our data suggest that the AGS algorithm could be used to help discriminating patients requiring high acenocoumarol doses to achieve stable anti-coagulation

VLDL Hydrolysis by Hepatic Lipase Regulates PPARδ Transcriptional Responses

PPARs (α,γ,δ) are a family of ligand-activated transcription factors that regulate energy balance, including lipid metabolism. Despite these critical functions, the integration between specific pathways of lipid metabolism and distinct PPAR responses remains obscure. Previous work has revealed that lipolytic pathways can activate PPARs. Whether hepatic lipase (HL), an enzyme that regulates VLDL and HDL catabolism, participates in PPAR responses is unknown.Using PPAR ligand binding domain transactivation assays, we found that HL interacted with triglyceride-rich VLDL (>HDL≫LDL, IDL) to activate PPARδ preferentially over PPARα or PPARγ, an effect dependent on HL catalytic activity. In cell free ligand displacement assays, VLDL hydrolysis by HL activated PPARδ in a VLDL-concentration dependent manner. Extended further, VLDL stimulation of HL-expressing HUVECs and FAO hepatoma cells increased mRNA expression of canonical PPARδ target genes, including adipocyte differentiation related protein (ADRP), angiopoietin like protein 4 and pyruvate dehydrogenase kinase-4. HL/VLDL regulated ADRP through a PPRE in the promoter region of this gene. In vivo, adenoviral-mediated hepatic HL expression in C57BL/6 mice increased hepatic ADRP mRNA levels by 30%. In ob/ob mice, a model with higher triglycerides than C57BL/6 mice, HL overexpression increased ADRP expression by 70%, demonstrating the importance of triglyceride substrate for HL-mediated PPARδ activation. Global metabolite profiling identified HL/VLDL released fatty acids including oleic acid and palmitoleic acid that were capable of recapitulating PPARδ activation and ADRP gene regulation in vitro.These data define a novel pathway involving HL hydrolysis of VLDL that activates PPARδ through generation of specific monounsaturated fatty acids. These data also demonstrate how integrating cell biology with metabolomic approaches provides insight into specific lipid mediators and pathways of lipid metabolism that regulate transcription

Quality of care assessment in geriatric evaluation and management units: construction of a chart review tool for a tracer condition

<p>Abstract</p> <p>Background</p> <p>The number of elderly people requiring hospital care is growing, so, quality and assessment of care for elders are emerging and complex areas of research. Very few validated and reliable instruments exist for the assessment of quality of acute care in this field. This study's objective was to create such a tool for Geriatric Evaluation and Management Units (GEMUs).</p> <p>Methods</p> <p>The methodology involved a reliability and feasibility study of a retrospective chart review on 934 older inpatients admitted in 49 GEMUs during the year 2002–2003 for fall-related trauma as a tracer condition. Pertinent indicators for a chart abstraction tool, the Geriatric Care Tool (GCT), were developed and validated according to five dimensions: access to care, comprehensiveness, continuity of care, patient-centred care and appropriateness. Consensus methods were used to develop the content. Participants were experts representing eight main health care professions involved in GEMUs from 19 different sites. Items associated with high quality of care at each step of the multidisciplinary management of patients admitted due to falls were identified. The GCT was tested for intra- and inter-rater reliability using 30 medical charts reviewed by each of three independent and blinded trained nurses. Kappa and agreement measures between pairs of chart reviewers were computed on an item-by-item basis.</p> <p>Results</p> <p>Three quarters of 169 items identifying the process of care, from the case history to discharge planning, demonstrated good agreement (kappa greater than 0.40 and agreement over 70%). Indicators for the appropriateness of care showed less reliability.</p> <p>Conclusion</p> <p>Content validity and reliability results, as well as the feasibility of the process, suggest that the chart abstraction tool can gather standardized and pertinent clinical information for further evaluating quality of care in GEMU using admission due to falls as a tracer condition. However, the GCT should be evaluated in other models of acute geriatric units and new strategies should be developed to improve reliability of peer assessments in characterizing the quality of care for elderly patients with complex conditions.</p

A Climatic Stability Approach to Prioritizing Global Conservation Investments

Climate change is impacting species and ecosystems globally. Many existing templates to identify the most important areas to conserve terrestrial biodiversity at the global scale neglect the future impacts of climate change. Unstable climatic conditions are predicted to undermine conservation investments in the future. This paper presents an approach to developing a resource allocation algorithm for conservation investment that incorporates the ecological stability of ecoregions under climate change. We discover that allocating funds in this way changes the optimal schedule of global investments both spatially and temporally. This allocation reduces the biodiversity loss of terrestrial endemic species from protected areas due to climate change by 22% for the period of 2002–2052, when compared to allocations that do not consider climate change. To maximize the resilience of global biodiversity to climate change we recommend that funding be increased in ecoregions located in the tropics and/or mid-elevation habitats, where climatic conditions are predicted to remain relatively stable. Accounting for the ecological stability of ecoregions provides a realistic approach to incorporating climate change into global conservation planning, with potential to save more species from extinction in the long term

Direct Presentation Is Sufficient for an Efficient Anti-Viral CD8+ T Cell Response

The extent to which direct- and cross-presentation (DP and CP) contribute to the priming of CD8+ T cell (TCD8+) responses to viruses is unclear mainly because of the difficulty in separating the two processes. Hence, while CP in the absence of DP has been clearly demonstrated, induction of an anti-viral TCD8+ response that excludes CP has never been purposely shown. Using vaccinia virus (VACV), which has been used as the vaccine to rid the world of smallpox and is proposed as a vector for many other vaccines, we show that DP is the main mechanism for the priming of an anti-viral TCD8+ response. These findings provide important insights to our understanding of how one of the most effective anti-viral vaccines induces immunity and should contribute to the development of novel vaccines

Decline of Birds in a Human Modified Coastal Dune Forest Landscape in South Africa

Previous studies demonstrate that old-growth forest remnants and vegetation regenerating after anthropogenic disturbance provide habitat for birds in a human modified coastal dune forest landscape in northern KwaZulu-Natal, South Africa. However, occurrence does not ensure persistence. Based on a 13-year monitoring database we calculated population trends for 37 bird species and general trends in overall bird density in different vegetation types. We evaluated species' characteristics as covariates of population trend and assessed changes in rainfall and proportional area and survey coverage per vegetation type. 76% of species assessed have declined, 57% significantly so at an average rate of 13.9% per year. Overall, bird density has fallen at 12.2% per year across old-growth forest and woody regenerating vegetation types. Changes in proportional area and coverage per vegetation type may partly explain trends for a few species but are unlikely to account for most. Below average rainfall may have contributed to bird declines. However, other possibilities warrant further investigation. Species with larger range extents tended to decline more sharply than did others, and these species may be responding to environmental changes on a broader geographical scale. Our results cast doubt on the future persistence of birds in this human modified landscape. More research is needed to elucidate the mechanisms driving population decline in the study area and to investigate whether the declines identified here are more widespread across the region and perhaps the continent