BEYOND CLINICAL GUIDELINES: HOW CARE PATHWAYS AND QUALITY-IMPROVEMENT METHODS CAN SUPPORT BETTER ALLERGY CARE

The increasing prevalence of allergic disease has resulted in the recognition of allergy as a global public health concern. Yet health services worldwide appear to be ill-equipped to deliver high-quality allergy care. Clinical guidelines have been developed to describe what high-quality care looks like for most allergic diseases. However, allergy guidelines do not describe how the delivery of such care is organised across clinicians and provider organisations with varying degrees of access to allergy expertise and clinical resources. In this article, we describe how care pathways can be used to improve the organisation and delivery of allergy care in accordance with the characteristics of allergic disease and local constraints in the health service. We then describe how quality-improvement methods can support the successful realisation of allergy care pathways in practice. Realising care pathways involves a highly complex process of changing the way care is practised and organised. This could involve developing a new service, clinical training or other interventions. Qualityimprovement methods were developed as a guide to navigate and support the process of change and improvement

Entropic forces drive self-organization and membrane fusion by SNARE proteins

SNARE proteins are the core of the cell’s fusion machinery and mediate virtually all known intracellular membrane fusion reactions on which exocytosis and trafficking depend. Fusion is catalyzed when vesicle-associated v-SNAREs form trans-SNARE complexes (“SNAREpins”) with target membrane-associated t-SNAREs, a zippering-like process releasing ∼65 kT per SNAREpin. Fusion requires several SNAREpins, but how they cooperate is unknown and reports of the number required vary widely. To capture the collective behavior on the long timescales of fusion, we developed a highly coarse-grained model that retains key biophysical SNARE properties such as the zippering energy landscape and the surface charge distribution. In simulations the ∼65-kT zippering energy was almost entirely dissipated, with fully assembled SNARE motifs but uncomplexed linker domains. The SNAREpins self-organized into a circular cluster at the fusion site, driven by entropic forces that originate in steric–electrostatic interactions among SNAREpins and membranes. Cooperative entropic forces expanded the cluster and pulled the membranes together at the center point with high force. We find that there is no critical number of SNAREs required for fusion, but instead the fusion rate increases rapidly with the number of SNAREpins due to increasing entropic forces. We hypothesize that this principle finds physiological use to boost fusion rates to meet the demanding timescales of neurotransmission, exploiting the large number of v-SNAREs available in synaptic vesicles. Once in an unfettered cluster, we estimate ≥15 SNAREpins are required for fusion within the ∼1-ms timescale of neurotransmitter release

Acromial stress fracture in a young wheelchair user with Charcot-Marie-Tooth disease: a case report

Acromial stress fractures are rare and have not been highlighted as a potential complication of wheelchair use. We report the case of a 22-year old female wheelchair bound patient with Charcot-Marie-Tooth disease who presented with a four-year history of shoulder pain which impaired mobility and quality of life. Plain radiographs showed a cortical irregularity of the acromion but no double-density sign. After CT scans a non-united acromial stress fracture was diagnosed. She had no other shoulder pathology. The new technique of using a superiorly closing wedge osteotomy with cancellous lag screw fixation was successful in correcting the mobile non-united acromial fragment and resolving her pain

Tidal and groundwater fluxes to a shallow, microtidal estuary : constraining inputs through field observations and hydrodynamic modeling

This paper is not subject to U.S. copyright. The definitive version was published in Estuaries and Coasts 35 (2012): 1285-1298, doi:10.1007/s12237-012-9515-x.Increased nutrient loading to estuaries has led to eutrophication, degraded water quality, and ecological transformations. Quantifying nutrient loads in systems with significant groundwater input can be difficult due to the challenge of measuring groundwater fluxes. We quantified tidal and freshwater fluxes over an 8-week period at the entrance of West Falmouth Harbor, Massachusetts, a eutrophic, groundwater-fed estuary. Fluxes were estimated from velocity and salinity measurements and a total exchange flow (TEF) methodology. Intermittent cross-sectional measurements of velocity and salinity were used to convert point measurements to cross-sectionally averaged values over the entire deployment (index relationships). The estimated mean freshwater flux (0.19 m3/s) for the 8-week period was mainly due to groundwater input (0.21 m3/s) with contributions from precipitation to the estuary surface (0.026 m3/s) and removal by evaporation (0.048 m3/s). Spring–neap variations in freshwater export that appeared in shorter-term averages were mostly artifacts of the index relationships. Hydrodynamic modeling with steady groundwater input demonstrated that while the TEF methodology resolves the freshwater flux signal, calibration of the index– salinity relationships during spring tide conditions only was responsible for most of the spring–neap signal. The mean freshwater flux over the entire period estimated from the combination of the index-velocity, index–salinity, and TEF calculations were consistent with the model, suggesting that this methodology is a reliable way of estimating freshwater fluxes in the estuary over timescales greater than the spring– neap cycle. Combining this type of field campaign with hydrodynamic modeling provides guidance for estimating both magnitude of groundwater input and estuarine storage of freshwater and sets the stage for robust estimation of the nutrient load in groundwater.Funding was provided by the USGS Coastal and Marine Geology Program and by National Science Foundation Award #0420575 from the Biocomplexity/Coupled Biogeochemical Cycles Program

Captive reptile mortality rates in the home and implications for the wildlife trade

The trade in wildlife and keeping of exotic pets is subject to varying levels of national and international regulation and is a topic often attracting controversy. Reptiles are popular exotic pets and comprise a substantial component of the live animal trade. High mortality of traded animals raises welfare concerns, and also has implications for conservation if collection from the wild is required to meet demand. Mortality of reptiles can occur at any stage of the trade chain from collector to consumer. However, there is limited information on mortality rates of reptiles across trade chains, particularly amongst final consumers in the home. We investigated mortality rates of reptiles amongst consumers using a specialised technique for asking sensitive questions, additive Randomised Response Technique (aRRT), as well as direct questioning (DQ). Overall, 3.6% of snakes, chelonians and lizards died within one year of acquisition. Boas and pythons had the lowest reported mortality rates of 1.9% and chameleons had the highest at 28.2%. More than 97% of snakes, 87% of lizards and 69% of chelonians acquired by respondents over five years were reported to be captive bred and results suggest that mortality rates may be lowest for captive bred individuals. Estimates of mortality from aRRT and DQ did not differ significantly which is in line with our findings that respondents did not find questions about reptile mortality to be sensitive. This research suggests that captive reptile mortality in the home is rather low, and identifies those taxa where further effort could be made to reduce mortality rate

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

Ribosome Distribution in HeLa Cells during the Cell Cycle

In this study, we employed a surface-specific antibody against the large ribosome subunit to investigate the distribution of ribosomes in cells during the cell cycle. The antibody, anti-L7n, was raised against an expansion segment (ES) peptide from the large subunit ribosomal protein L7, and its ribosome-surface specificity was evident from the positive immuno-reactivity of ribosome particles and the detection of 60 S immune-complex formation by an immuno-electron microscopy. Using immunofluorescent staining, we have microscopically revealed that ribosomes are dispersed in the cytoplasm of cells throughout all phases of the cell cycle, except at the G2 phase where ribosomes show a tendency to gather toward the nuclear envelope. The finding in G2 cells was confirmed by electron microscopy using a morphometric assay and paired t test. Furthermore, further observations have shown that ribosomes are not distributed immune-fluorescently with nuclear envelope markers including the nuclear pore complex, the integral membrane protein gp210, the inner membrane protein lamin B2, and the endoplasm reticulum membrane during cell division we propose that the mechanism associated with ribosome segregation into daughter cells could be independent of the processes of disassembly and reassembly of the nuclear envelope

Hypothalamic over-expression of VGF in the Siberian hamster increases energy expenditure and reduces body weight gain

VGF (non-acronymic) was first highlighted to have a role in energy homeostasis through experiments involving dietary manipulation in mice. Fasting increased VGF mRNA in the Arc and levels were subsequently reduced upon refeeding. This anabolic role for VGF was supported by observations in a VGF null (VGF-/-) mouse and in the diet-induced and gold-thioglucose obese mice. However, this anabolic role for VGF has not been supported by a number of subsequent studies investigating the physiological effects of VGF-derived peptides. Intracerebroventricular (ICV) infusion of TLQP-21 increased resting energy expenditure and rectal temperature in mice and protected against diet-induced obesity. Similarly, ICV infusion of TLQP-21 into Siberian hamsters significantly reduced body weight, but this was due to a decrease in food intake, with no effect on energy expenditure. Subsequently NERP-2 was shown to increase food intake in rats via the orexin system, suggesting opposing roles for these VGF-derived peptides. Thus to further elucidate the role of hypothalamic VGF in the regulation of energy homeostasis we utilised a recombinant adeno-associated viral vector to over-express VGF in adult male Siberian hamsters, thus avoiding any developmental effects or associated functional compensation. Initially, hypothalamic over-expression of VGF in adult Siberian hamsters produced no effect on metabolic parameters, but by 12 weeks post-infusion hamsters had increased oxygen consumption and a tendency to increased carbon dioxide production; this attenuated body weight gain, reduced interscapular white adipose tissue and resulted in a compensatory increase in food intake. These observed changes in energy expenditure and food intake were associated with an increase in the hypothalamic contents of the VGF-derived peptides AQEE, TLQP and NERP-2. The complex phenotype of the VGF-/- mice is a likely consequence of global ablation of the gene and its derived peptides during development, as well as in the adult

Decadal-timescale estuarine geomorphic change under future scenarios of climate and sediment supply

© The Authors, 2009. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in Estuaries and Coasts 33 (2010): 15-29, doi:10.1007/s12237-009-9244-y.Future estuarine geomorphic change, in response to climate change, sea-level rise, and watershed sediment supply, may govern ecological function, navigation, and water quality. We estimated geomorphic changes in Suisun Bay, CA, under four scenarios using a tidal-timescale hydrodynamic/sediment transport model. Computational expense and data needs were reduced using the morphological hydrograph concept and the morphological acceleration factor. The four scenarios included (1) present-day conditions; (2) sea-level rise and freshwater flow changes of 2030; (3) sea-level rise and decreased watershed sediment supply of 2030; and (4) sea-level rise, freshwater flow changes, and decreased watershed sediment supply of 2030. Sea-level rise increased water levels thereby reducing wave-induced bottom shear stress and sediment redistribution during the wind-wave season. Decreased watershed sediment supply reduced net deposition within the estuary, while minor changes in freshwater flow timing and magnitude induced the smallest overall effect. In all future scenarios, net deposition in the entire estuary and in the shallowest areas did not keep pace with sea-level rise, suggesting that intertidal and wetland areas may struggle to maintain elevation. Tidal-timescale simulations using future conditions were also used to infer changes in optical depth: though sea-level rise acts to decrease mean light irradiance, decreased suspended-sediment concentrations increase irradiance, yielding small changes in optical depth. The modeling results also assisted with the development of a dimensionless estuarine geomorphic number representing the ratio of potential sediment import forces to sediment export forces; we found the number to be linearly related to relative geomorphic change in Suisun Bay. The methods implemented here are widely applicable to evaluating future scenarios of estuarine change over decadal timescales.This study was supported by the US Geological Survey’s Priority Ecosystems Science program, CALFED Bay/ Delta Program, and the University of California Center for Water Resources