388 research outputs found
From programme theory to logic models for multispecialty community providers: a realist evidence synthesis
This is the final version. Available from the publisher via the DOI in this record.Background: The NHS policy of constructing multispecialty community providers (MCPs) rests on a complex
set of assumptions about how health systems can replace hospital use with enhanced primary care for
people with complex, chronic or multiple health problems, while contributing savings to health-care
budgets.
Objectives: To use policy-makers’ assumptions to elicit an initial programme theory (IPT) of how MCPs can
achieve their outcomes and to compare this with published secondary evidence and revise the programme
theory accordingly.
Design: Realist synthesis with a three-stage method: (1) for policy documents, elicit the IPT underlying the
MCP policy, (2) review and synthesise secondary evidence relevant to those assumptions and (3) compare
the programme theory with the secondary evidence and, when necessary, reformulate the programme
theory in a more evidence-based way.
Data sources: Systematic searches and data extraction using (1) the Health Management Information
Consortium (HMIC) database for policy statements and (2) topically appropriate databases, including
MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PsycINFO, the Cumulative Index to Nursing
and Allied Health Literature (CINAHL) and Applied Social Sciences Index and Abstracts (ASSIA). A total of
1319 titles and abstracts were reviewed in two rounds and 116 were selected for full-text data extraction.
We extracted data using a formal data extraction tool and synthesised them using a framework reflecting
the main policy assumptions.
Results: The IPT of MCPs contained 28 interconnected context–mechanism–outcome relationships.
Few policy statements specified what contexts the policy mechanisms required. We found strong
evidence supporting the IPT assumptions concerning organisational culture, interorganisational network
management, multidisciplinary teams (MDTs), the uses and effects of health information technology (HIT)
in MCP-like settings, planned referral networks, care planning for individual patients and the diversion
of patients from inpatient to primary care. The evidence was weaker, or mixed (supporting some of
the constituent assumptions but not others), concerning voluntary sector involvement, the effects of
preventative care on hospital admissions and patient experience, planned referral networks and demand management systems. The evidence about the effects of referral reductions on costs was equivocal.
We found no studies confirming that the development of preventative care would reduce demands on
inpatient services. The IPT had overlooked certain mechanisms relevant to MCPs, mostly concerning MDTs
and the uses of HITs.
Limitations: The studies reviewed were limited to Organisation for Economic Co-operation and
Development countries and, because of the large amount of published material, the period 2014–16,
assuming that later studies, especially systematic reviews, already include important earlier findings.
No empirical studies of MCPs yet existed.
Conclusions: Multidisciplinary teams are a central mechanism by which MCPs (and equivalent networks
and organisations) work, provided that the teams include the relevant professions (hence, organisations)
and, for care planning, individual patients. Further primary research would be required to test elements of
the revised logic model, in particular about (1) how MDTs and enhanced general practice compare and
interact, or can be combined, in managing referral networks and (2) under what circumstances diverting
patients from in-patient to primary care reduces NHS costs and improves the quality of patient experience.National Institute for Health Research (NIHR
Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia.
The role of Hedgehog signaling in normal and malignant T-cell development is controversial. Recently, Hedgehog pathway mutations have been described in T-ALL, but whether mutational activation of Hedgehog signaling drives T-cell transformation is unknown, hindering the rationale for therapeutic intervention. Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in human T-ALL, and drive oncogenic transformation in a zebrafish model of the disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases, most commonly affecting its negative regulator PTCH1. Hedgehog mutations were associated with resistance to induction chemotherapy (P = 0.009). Transduction of wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a phenotype that was reversed by downstream Hedgehog pathway activation (P = 0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian cells induced aberrant regulation of Hedgehog signaling, indicating that these mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale for targeted therapy in this disease
Career Success in Different Countries : Reflections on the 5C Project
fi=vertaisarvioitu|en=peerReviewed
Searching for Programme theories for a realist evaluation: a case study comparing an academic database search and a simple Google search
Background:
Realist methodologies are increasingly being used to evaluate complex interventions in health and social care. Programme theory (ideas and assumptions of how a particular intervention works) development is the first step in a realist evaluation or a realist synthesis, with literature reviews providing important evidence to support this. Deciding how to search for programme theories is challenging and there is limited guidance available. Using an example of identifying programme theories for a realist evaluation of Pressure Ulcer Risk Assessment Instruments in clinical practice, the authors explore and compare several different approaches to literature searching and highlight important methodological considerations for those embarking on a programme theory review.
Methods:
We compared the performance of an academic database search with a simple Google search and developed an optimised search strategy for the identification primary references (i.e. documents providing the clearest examples of programme theories) associated with the use of Pressure Ulcer Risk Assessment Instruments (PU-RAIs). We identified the number of primary references and the total number of references retrieved per source. We then calculated the number needed to read (NNR) expressed as the total number of titles and abstracts screened to identify one relevant reference from each source.
Results:
The academic database search (comprising CINAHL, The Cochrane Library, EMBASE, HMIC, Medline) identified 2 /10 primary references with a NNR of 1395.The Google search identified 7/10 primary references with a NNR of 10.1. The combined NNR was 286.3. The optimised search combining Google and CINAHL identified 10/10 primary references with a NNR of 40.2.
Conclusion:
The striking difference between the efficiency of the review’s academic database and Google searches in finding relevant references prompted an in-depth comparison of the two types of search. The findings indicate the importance of including grey literature sources such as Google in this particular programme theory search, while acknowledging the need for transparency of methods. Further research is needed to facilitate improved guidance for programme theory searches to enhance practice in the realist field and to save researcher time and therefore resource
Benchmarking natural-language parsers for biological applications using dependency graphs
BACKGROUND: Interest is growing in the application of syntactic parsers to natural language processing problems in biology, but assessing their performance is difficult because differences in linguistic convention can falsely appear to be errors. We present a method for evaluating their accuracy using an intermediate representation based on dependency graphs, in which the semantic relationships important in most information extraction tasks are closer to the surface. We also demonstrate how this method can be easily tailored to various application-driven criteria. RESULTS: Using the GENIA corpus as a gold standard, we tested four open-source parsers which have been used in bioinformatics projects. We first present overall performance measures, and test the two leading tools, the Charniak-Lease and Bikel parsers, on subtasks tailored to reflect the requirements of a system for extracting gene expression relationships. These two tools clearly outperform the other parsers in the evaluation, and achieve accuracy levels comparable to or exceeding native dependency parsers on similar tasks in previous biological evaluations. CONCLUSION: Evaluating using dependency graphs allows parsers to be tested easily on criteria chosen according to the semantics of particular biological applications, drawing attention to important mistakes and soaking up many insignificant differences that would otherwise be reported as errors. Generating high-accuracy dependency graphs from the output of phrase-structure parsers also provides access to the more detailed syntax trees that are used in several natural-language processing techniques
Measurement of the Polarized Structure Function for in the Resonance Region
The polarized longitudinal-transverse structure function
has been measured in the resonance region at and 0.65
GeV. Data for the reaction were taken at Jefferson Lab
with the CEBAF Large Acceptance Spectrometer (CLAS) using longitudinally
polarized electrons at an energy of 1.515 GeV. For the first time a complete
angular distribution was measured, permitting the separation of different
non-resonant amplitudes using a partial wave analysis. Comparison with previous
beam asymmetry measurements at MAMI indicate a deviation from the predicted
dependence of using recent phenomenological
models.Comment: 5 pages, LaTex, 4 eps figures: to be published in PRC/Rapid
Communications. Version 2 has revised Q^2 analysi
Survey of A_LT' asymmetries in semi-exclusive electron scattering on He4 and C12
Single spin azimuthal asymmetries A_LT' were measured at Jefferson Lab using
2.2 and 4.4 GeV longitudinally polarized electrons incident on He4 and C12
targets in the CLAS detector. A_LT' is related to the imaginary part of the
longitudinal-transverse interference and in quasifree nucleon knockout it
provides an unambiguous signature for final state interactions (FSI).
Experimental values of A_LT' were found to be below 5%, typically |A_LT'| < 3%
for data with good statistical precision. Optical Model in Eikonal
Approximation (OMEA) and Relativistic Multiple-Scattering Glauber Approximation
(RMSGA) calculations are shown to be consistent with the measured asymmetries.Comment: 9 pages, 5 figure
Onset of asymptotic scaling in deuteron photodisintegration
We investigate the transition from the nucleon-meson to quark-gluon
description of the strong interaction using the photon energy dependence of the
differential cross section for photon energies above 0.5 GeV and
center-of-mass proton angles between and . A possible
signature for this transition is the onset of cross section scaling
with the total energy squared, , at some proton transverse momentum, .
The results show that the scaling has been reached for proton transverse
momentum above about 1.1 GeV/c. This may indicate that the quark-gluon regime
is reached above this momentum.Comment: Accepted by PRL; 5 pages, 2 figure
First Measurement of Transferred Polarization in the Exclusive e p --> e' K+ Lambda Reaction
The first measurements of the transferred polarization for the exclusive ep
--> e'K+ Lambda reaction have been performed in Hall B at the Thomas Jefferson
National Accelerator Facility using the CLAS spectrometer. A 2.567 GeV electron
beam was used to measure the hyperon polarization over a range of Q2 from 0.3
to 1.5 (GeV/c)2, W from 1.6 to 2.15 GeV, and over the full center-of-mass
angular range of the K+ meson. Comparison with predictions of hadrodynamic
models indicates strong sensitivity to the underlying resonance contributions.
A non-relativistic quark model interpretation of our data suggests that the
s-sbar quark pair is produced with spins predominantly anti-aligned.
Implications for the validity of the widely used 3P0 quark-pair creation
operator are discussed.Comment: 6 pages, 4 figure
Single pi+ Electroproduction on the Proton in the First and Second Resonance Regions at 0.25GeV^2 < Q^2 < 0.65GeV^2 Using CLAS
The ep -> e'pi^+n reaction was studied in the first and second nucleon
resonance regions in the 0.25 GeV^2 < Q^2 < 0.65 GeV^2 range using the CLAS
detector at Thomas Jefferson National Accelerator Facility. For the first time
the absolute cross sections were measured covering nearly the full angular
range in the hadronic center-of-mass frame. The structure functions sigma_TL,
sigma_TT and the linear combination sigma_T+epsilon*sigma_L were extracted by
fitting the phi-dependence of the measured cross sections, and were compared to
the MAID and Sato-Lee models.Comment: Accepted for publication in PR
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