A global evaluation of the regional spatial variability of column integrated CO 2 distributions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95294/1/jgrd14612.pd

Using next-generation sequencing for high resolution multiplex analysis of copy number variation from nanogram quantities of DNA from formalin-fixed paraffin-embedded specimens

The use of next-generation sequencing technologies to produce genomic copy number data has recently been described. Most approaches, however, reply on optimal starting DNA, and are therefore unsuitable for the analysis of formalin-fixed paraffin-embedded (FFPE) samples, which largely precludes the analysis of many tumour series. We have sought to challenge the limits of this technique with regards to quality and quantity of starting material and the depth of sequencing required. We confirm that the technique can be used to interrogate DNA from cell lines, fresh frozen material and FFPE samples to assess copy number variation. We show that as little as 5 ng of DNA is needed to generate a copy number karyogram, and follow this up with data from a series of FFPE biopsies and surgical samples. We have used various levels of sample multiplexing to demonstrate the adjustable resolution of the methodology, depending on the number of samples and available resources. We also demonstrate reproducibility by use of replicate samples and comparison with microarray-based comparative genomic hybridization (aCGH) and digital PCR. This technique can be valuable in both the analysis of routine diagnostic samples and in examining large repositories of fixed archival material

History and symptom taking in contact lens fitting and aftercare.

AIM: To appraise history and symptom taking for contact lens consultations, to determine current practice and to make recommendations for best practice. METHOD: The peer reviewed academic literature was reviewed and the results informed a survey completed by 256 eye care practitioners (ECPs) on their current practice and influences. RESULTS: The last eye-test date, last contact lens aftercare (for existing wearers) and reason for visit are key questions for most ECPs. Detailed use of contact lens questions are more commonly applied in aftercares than when refitting patients who have previously discontinued wear (87% vs 56% use), whereas questions on ocular and general history, medication and lifestyle were generally more commonly utilised for new patients than in aftercares (72% vs 50%). 75% of ECPs requested patients bring a list of their medication to appointments. Differential diagnosis questioning was thorough in most ECPs (87% of relevant questions asked). Attempts to optimise compliance included oral instruction (95% always) and written patient instructions (95% at least sometimes). Abbreviations were used by 39% of respondents (26% used ones provided by a professional body). CONCLUSION: There is scope for more consistency in history and symptom taking for contact lens consultations and recommendations are made

Pros and cons of a prion-like pathogenesis in Parkinson's disease

Background: Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder which affects widespread areas of the brainstem, basal ganglia and cerebral cortex. A number of proteins are known to accumulate in parkinsonian brains including ubiquitin and alpha-synuclein. Prion diseases are sporadic, genetic or infectious disorders with various clinical and histopathological features caused by prion proteins as infectious proteinaceous particles transmitting a misfolded protein configuration through brain tissue. The most important form is Creutzfeldt-Jakob disease which is associated with a self-propagating pathological precursor form of the prion protein that is physiologically widely distributed in the central nervous system. Discussion: It has recently been found that alpha-synuclein may behave similarly to the prion precursor and propagate between cells. The post-mortem proof of alpha-synuclein containing Lewy bodies in embryonic dopamine cells transplants in PD patient suggests that the misfolded protein might be transmitted from the diseased host to donor neurons reminiscent of prion behavior. The involvement of the basal ganglia and brainstem in the degenerative process are other congruencies between Parkinson's and Creutzfeldt-Jakob disease. However, a number of issues advise caution before categorizing Parkinson's disease as a prion disorder, because clinical appearance, brain imaging, cerebrospinal fluid and neuropathological findings exhibit fundamental differences between both disease entities. Most of all, infectiousness, a crucial hallmark of prion diseases, has never been observed in PD so far. Moreover, the cellular propagation of the prion protein has not been clearly defined and it is, therefore, difficult to assess the molecular similarities between the two disease entities. Summary: At the current state of knowledge, the molecular pathways of transmissible pathogenic proteins are not yet fully understood. Their exact involvement in the pathophysiology of prion disorders and neurodegenerative diseases has to be further investigated in order to elucidate a possible overlap between both disease categories that are currently regarded as distinct entities

Biological and climate controls on North Atlantic marine carbon dynamics over the last millennium: Insights from an absolutely-dated shell based record from the North Icelandic Shelf

Given the rapid increase in atmospheric carbon dioxide concentrations (pCO2) over the industrial era, there is a pressing need to construct long‐term records of natural carbon cycling prior to this perturbation and to develop a more robust understanding of the role the oceans play in the sequestration of atmospheric carbon. Here we reconstruct the past biological and climate controls on the carbon isotopic (δ13Cshell) composition of the North Icelandic shelf waters over the last millennium, derived from the shells of the long‐lived marine bivalve mollusk Arctica islandica. Variability in the annually resolved δ13Cshell record is dominated by multidecadal variability with a negative trend (−0.003 ± 0.002‰ yr−1) over the industrial era (1800–2000 Common Era). This trend is consistent with the marine Suess effect brought about by the sequestration of isotopically light carbon (δ13C of CO2) derived from the burning of fossil fuels. Comparison of the δ13Cshell record with Contemporaneous proxy archives, over the last millennium, and instrumental data over the twentieth century, highlights that both biological (primary production) and physical environmental factors, such as relative shifts in the proportion of Subpolar Mode Waters and Arctic Intermediate Waters entrained onto the North Icelandic shelf, atmospheric circulation patterns associated with the winter North Atlantic Oscillation, and sea surface temperature and salinity of the subpolar gyre, are the likely mechanisms that contribute to natural variations in seawater δ13C variability on the North Icelandic shelf. Contrasting δ13C fractionation processes associated with these biological and physical mechanisms likely cause the attenuated marine Suess effect signal at this locality

Multidecadal CO2uptake variability of the North Atlantic

The multidecadal variability of air-sea CO(2)fluxes in the North Atlantic under preindustrial atmospheric CO(2) conditions is simulated, using a coupled biogeochemical/circulation model driven by long-term surface forcing reconstructed from the leading modes of sea level pressure observations from 1850 to 2000. Heat fluxes are of great importance for the multidecadal CO(2) fluctuations, about equal in magnitude to wind stress, in contrast to their less prominent role for CO(2) flux variability on interannual timescales. Another difference, compared to higher frequencies, is the dominance of the North Atlantic Oscillation in driving the variability of the air-sea CO(2) fluxes. Two spatially distinct regimes lead to large anomalies in the CO(2) fluxes but compensate to a large degree. The first regime is advective and has its clear signature southeast of Greenland while the second one, in the vicinity of the Labrador Sea and off Newfoundland, is convective. In both regimes, the multidecadal CO(2) fluctuations are driven mainly by variations in temperature, salinity, and DIC content at the sea surface while the role of the biological pump is of minor importance in this particular model. The magnitude of the simulated multidecadal CO(2) uptake changes is on the order of 0.02 Pg C/yr and amounts to 10-15% of the estimated annual anthropogenic CO(2) uptake of the North Atlantic

An ensemble data assimilation system to estimate CO2 surface fluxes from atmospheric trace gas observations

We present a data assimilation system to estimate surface fluxes of CO2 and other trace gases from observations of their atmospheric abundances. The system is based on ensemble data assimilation methods under development for Numerical Weather Prediction (NWP) and is the first of its kind to be used for CO2 flux estimation. The system was developed to overcome computational limitations encountered when a large number of observations are used to estimate a large number of unknown surface fluxes. The ensemble data assimilation approach is attractive because it returns an approximation of the covariance, does not need an adjoint model or other linearization of the observation operator, and offers the possibility to optimize fluxes of chemically active trace gases (e.g., CH4, CO) in the same framework. We assess the performance of this new system in a pseudodata experiment that resembles the real problem we will apply this system to. The sensitivity of the method to the choice of several parameters such as the assimilation window size and the number of ensemble members is investigated. We conclude that the system is able to provide satisfactory flux estimates for the relatively large scales resolved by our current observing network and that the loss of information in the approximated covariances is an acceptable price to pay for the efficient computation of a large number of surface fluxes. The full potential of this data assimilation system will be used for near–real time operational estimates of North American CO2 fluxes. This will take advantage of the large amounts of atmospheric data that will be collected by NOAA-CMDL in conjunction with the implementation of the North American Carbon Program (NACP)

A realist analysis of hospital patient safety in Wales:Applied learning for alternative contexts from a multisite case study

Background: Hospital patient safety is a major social problem. In the UK, policy responses focus on the introduction of improvement programmes that seek to implement evidence-based clinical practices using the Model for Improvement, Plan-Do-Study-Act cycle. Empirical evidence that the outcomes of such programmes vary across hospitals demonstrates that the context of their implementation matters. However, the relationships between features of context and the implementation of safety programmes are both undertheorised and poorly understood in empirical terms. Objectives: This study is designed to address gaps in conceptual, methodological and empirical knowledge about the influence of context on the local implementation of patient safety programmes. Design: We used concepts from critical realism and institutional analysis to conduct a qualitative comparative-intensive case study involving 21 hospitals across all seven Welsh health boards. We focused on the local implementation of three focal interventions from the 1000 Lives+ patient safety programme: Improving Leadership for Quality Improvement, Reducing Surgical Complications and Reducing Health-care Associated Infection. Our main sources of data were 160 semistructured interviews, observation and 1700 health policy and organisational documents. These data were analysed using the realist approaches of abstraction, abduction and retroduction. Setting: Welsh Government and NHS Wales. Participants: Interviews were conducted with 160 participants including government policy leads, health managers and professionals, partner agencies with strategic oversight of patient safety, advocacy groups and academics with expertise in patient safety. Main outcome measures: Identification of the contextual factors pertinent to the local implementation of the 1000 Lives+ patient safety programme in Welsh NHS hospitals. Results: An innovative conceptual framework harnessing realist social theory and institutional theory was produced to address challenges identified within previous applications of realist inquiry in patient safety research. This involved the development and use of an explanatory intervention–context–mechanism–agency–outcome (I-CMAO) configuration to illustrate the processes behind implementation of a change programme. Our findings, illustrated by multiple nested I-CMAO configurations, show how local implementation of patient safety interventions are impacted and modified by particular aspects of context: specifically, isomorphism, by which an intervention becomes adapted to the environment in which it is implemented; institutional logics, the beliefs and values underpinning the intervention and its source, and their perceived legitimacy among different groups of health-care professionals; and the relational structure and power dynamics of the functional group, that is, those tasked with implementing the initiative. This dynamic interplay shapes and guides actions leading to the normalisation or the rejection of the patient safety programme. Conclusions: Heightened awareness of the influence of context on the local implementation of patient safety programmes is required to inform the design of such interventions and to ensure their effective implementation and operationalisation in the day-to-day practice of health-care teams. Future work is required to elaborate our conceptual model and findings in similar settings where different interventions are introduced, and in different settings where similar innovations are implemented. Funding: The National Institute for Health Research Health Services and Delivery Research programme

Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo

Meeting Abstracts: Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo Clearwater Beach, FL, USA. 9-11 June 201

the Information Literacy Community: A Collaboration among Students, Professors, and Librarians

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