Which patients are not included in the English Cancer Waiting Times monitoring dataset, 2009-2013? Implications for use of the data in research.

BACKGROUND: Cancer waiting time targets are routinely monitored in England, but the Cancer Waiting Times monitoring dataset (CWT) does not include all eligible patients, introducing scope for bias. METHODS: Data from adults diagnosed in England (2009-2013) with colorectal, lung, or ovarian cancer were linked from CWT to cancer registry, mortality, and Hospital Episode Statistics data. We present demographic characteristics and net survival for patients who were and were not included in CWT. RESULTS: A CWT record was found for 82% of colorectal, 76% of lung, and 77% of ovarian cancer patients. Patients not recorded in CWT were more likely to be in the youngest or oldest age groups, have more comorbidities, have been diagnosed through emergency presentation, have late or missing stage, and have much poorer survival. CONCLUSIONS: Researchers and policy-makers should be aware of the limitations in the completeness and representativeness of CWT, and draw conclusions with appropriate caution

Choice of geographic unit influences socioeconomic inequalities in breast cancer survival

Socioeconomic differences in age-standardised crude survival for women diagnosed with breast cancer during 1991–1999 in England were influenced by the population of the geographic area used to assign the deprivation index, but not by the choice of index

Towards the development of novel Trypanosoma brucei RNA editing ligase 1 inhibitors

Abstract Background Trypanosoma brucei (T. brucei) is an infectious agent for which drug development has been largely neglected. We here use a recently developed computer program called AutoGrow to add interacting molecular fragments to S5, a known inhibitor of the validated T. brucei drug target RNA editing ligase 1, in order to improve its predicted binding affinity. Results The proposed binding modes of the resulting compounds mimic that of ATP, the native substrate, and provide insights into novel protein-ligand interactions that may be exploited in future drug-discovery projects. Conclusions We are hopeful that these new predicted inhibitors will aid medicinal chemists in developing novel therapeutics to fight human African trypanosomiasis

A study of general practitioners' perspectives on electronic medical records systems in NHS Scotland

<b>Background</b> Primary care doctors in NHSScotland have been using electronic medical records within their practices routinely for many years. The Scottish Health Executive eHealth strategy (2008-2011) has recently brought radical changes to the primary care computing landscape in Scotland: an information system (GPASS) which was provided free-of-charge by NHSScotland to a majority of GP practices has now been replaced by systems provided by two approved commercial providers. The transition to new electronic medical records had to be completed nationally across all health-boards by March 2012. <p></p><b> Methods</b> We carried out 25 in-depth semi-structured interviews with primary care doctors to elucidate GPs' perspectives on their practice information systems and collect more general information on management processes in the patient surgical pathway in NHSScotland. We undertook a thematic analysis of interviewees' responses, using Normalisation Process Theory as the underpinning conceptual framework. <p></p> <b>Results</b> The majority of GPs' interviewed considered that electronic medical records are an integral and essential element of their work during the consultation, playing a key role in facilitating integrated and continuity of care for patients and making clinical information more accessible. However, GPs expressed a number of reservations about various system functionalities - for example: in relation to usability, system navigation and information visualisation. <b>Conclusion </b>Our study highlights that while electronic information systems are perceived as having important benefits, there remains substantial scope to improve GPs' interaction and overall satisfaction with these systems. Iterative user-centred improvements combined with additional training in the use of technology would promote an increased understanding, familiarity and command of the range of functionalities of electronic medical records among primary care doctors

Amazonian chemical weathering rate derived from stony meteorite finds at Meridiani Planum on Mars

© The Author(s) 2016.Spacecraft exploring Mars such as the Mars Exploration Rovers Spirit and Opportunity, as well as the Mars Science Laboratory or Curiosity rover, have accumulated evidence for wet and habitable conditions on early Mars more than 3 billion years ago. Current conditions, by contrast, are cold, extremely arid and seemingly inhospitable. To evaluate exactly how dry today's environment is, it is important to understand the ongoing current weathering processes. Here we present chemical weathering rates determined for Mars. We use the oxidation of iron in stony meteorites investigated by the Mars Exploration Rover Opportunity at Meridiani Planum. Their maximum exposure age is constrained by the formation of Victoria crater and their minimum age by erosion of the meteorites. The chemical weathering rates thus derived are ~1 to 4 orders of magnitude slower than that of similar meteorites found in Antarctica where the slowest rates are observed on Earth

Evaluation of stability of directly standardized rates for sparse data using simulation methods.

Background Directly standardized rates (DSRs) adjust for different age distributions in different populations and enable, say, the rates of disease between the populations to be directly compared. They are routinely published but there is concern that a DSR is not valid when it is based on a “small” number of events. The aim of this study was to determine the value at which a DSR should not be published when analyzing real data in England. Methods Standard Monte Carlo simulation techniques were used assuming the number of events in 19 age groups (i.e., 0–4, 5–9, ... 90+ years) follow independent Poisson distributions. The total number of events, age specific risks, and the population sizes in each age group were varied. For each of 10,000 simulations the DSR (using the 2013 European Standard Population weights), together with the coverage of three different methods (normal approximation, Dobson, and Tiwari modified gamma) of estimating the 95% confidence intervals (CIs), were calculated. Results The normal approximation was, as expected, not suitable for use when fewer than 100 events occurred. The Tiwari method and the Dobson method of calculating confidence intervals produced similar estimates and either was suitable when the expected or observed numbers of events were 10 or greater. The accuracy of the CIs was not influenced by the distribution of the events across categories (i.e., the degree of clustering, the age distributions of the sampling populations, and the number of categories with no events occurring in them). Conclusions DSRs should not be given when the total observed number of events is less than 10. The Dobson method might be considered the preferred method due to the formulae being simpler than that of the Tiwari method and the coverage being slightly more accurate

The RNA Binding Protein SAM68 Transiently Localizes in the Chromatoid Body of Male Germ Cells and Influences Expression of Select MicroRNAs

The chromatoid body (CB) is a unique structure of male germ cells composed of thin filaments that condense into a perinuclear organelle after meiosis. Due to the presence of proteins involved in different steps of RNA metabolism and of different classes of RNAs, including microRNAs (miRNAs), the CB has been recently suggested to function as an RNA processing centre. Herein, we show that the RNA binding protein SAM68 transiently localizes in the CB, in concomitance with the meiotic divisions of mouse spermatocytes. Precise staging of the seminiferous tubules and co-localization studies with MVH and MILI, two well recognized CB markers, documented that SAM68 transiently associates with the CB in secondary spermatocytes and early round spermatids. Furthermore, although SAM68 co-immunoprecipitated with MVH in secondary spermatocytes, its ablation did not affect the proper localization of MVH in the CB. On the other hand, ablation of the CB constitutive component MIWI did not impair association of SAM68 with the CB. Isolation of CBs from Sam68 wild type and knockout mouse testes and comparison of their protein content by mass spectrometry indicated that Sam68 ablation did not cause overall alterations in the CB proteome. Lastly, we found that SAM68 interacts with DROSHA and DICER in secondary spermatocytes and early round spermatids and that a subset of miRNAs were altered in Sam68−/−germ cells. These results suggest a novel role for SAM68 in the miRNA pathway during spermatogenesis

Engaging stakeholders in rehabilitation research: a scoping review of strategies used in partnerships and evaluation of impacts

Abstract: Purpose: To describe how stakeholder engagement has been undertaken and evaluated in rehabilitation research. Methods: A scoping review of the scientific literature using five search strategies. Quantitative and qualitative analyses using extracted data. Interpretation of results was iteratively discussed within the team, which included a parent stakeholder. Results: Searches identified 101 candidate papers; 28 were read in full to assess eligibility and 19 were included in the review. People with disabilities and their families were more frequently involved compared to other stakeholders. Stakeholders were often involved in planning and evaluating service delivery. A key issue was identifying stakeholders; strategies used to support their involvement included creating committees, organizing meetings, clarifying roles and offering training. Communication, power sharing and resources influenced how stakeholders could be engaged in the research. Perceived outcomes of stakeholder engagement included the creation of partnerships, facilitating the research process and the application of the results, and empowering stakeholders. Stakeholder engagement outcomes were rarely formally evaluated. Conclusions: There is a great interest in rehabilitation to engage stakeholders in the research process. However, further evidence is needed to identify effective strategies for meaningful stakeholder engagement that leads to more useful research that positively impacts practice. Implications for Rehabilitation Using several strategies to engage various stakeholders throughout the research process is thought to increase the quality of the research and the rehabilitation process by developing proposals and programs responding better to their needs. Engagement strategies need to be better reported and evaluated in the literature. Engagement facilitate uptake of research findings by increasing stakeholders' awareness of the evidence, the resources available and their own ability to act upon a situation. Factors influencing opportunities for stakeholder engagement need to be better understood

Exponential Random Graph Modeling for Complex Brain Networks

Exponential random graph models (ERGMs), also known as p* models, have been utilized extensively in the social science literature to study complex networks and how their global structure depends on underlying structural components. However, the literature on their use in biological networks (especially brain networks) has remained sparse. Descriptive models based on a specific feature of the graph (clustering coefficient, degree distribution, etc.) have dominated connectivity research in neuroscience. Corresponding generative models have been developed to reproduce one of these features. However, the complexity inherent in whole-brain network data necessitates the development and use of tools that allow the systematic exploration of several features simultaneously and how they interact to form the global network architecture. ERGMs provide a statistically principled approach to the assessment of how a set of interacting local brain network features gives rise to the global structure. We illustrate the utility of ERGMs for modeling, analyzing, and simulating complex whole-brain networks with network data from normal subjects. We also provide a foundation for the selection of important local features through the implementation and assessment of three selection approaches: a traditional p-value based backward selection approach, an information criterion approach (AIC), and a graphical goodness of fit (GOF) approach. The graphical GOF approach serves as the best method given the scientific interest in being able to capture and reproduce the structure of fitted brain networks

Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding

Background: Atherosclerosis is an inflammatory process that develops in individuals with known risk factors that include hypertension and hyperlipidaemia, influenced by diet. However, the interplay between diet, inflammatory mechanisms and vascular risk factors requires further research. We hypothesised that interleukin-1 (IL-1) signaling in the vessel wall would raise arterial blood pressure and promote atheroma. Methodology/Principal Findings: Apoe(-/-) and Apoe(-/-)/IL-1R1(-/-) mice were fed high fat diets for 8 weeks, and their blood pressure and atherosclerosis development measured. Apoe(-/-)/IL-R1(-/-) mice had a reduced blood pressure and significantly less atheroma than Apoe(-/-) mice. Selective loss of IL-1 signaling in the vessel wall by bone marrow transplantation also reduced plaque burden (p<0.05). This was associated with an IL-1 mediated loss of endothelium-dependent relaxation and an increase in vessel wall Nox 4. Inhibition of IL-1 restored endothelium-dependent vasodilatation and reduced levels of arterial oxidative stress. Conclusions/Significance: The IL-1 cytokine system links atherogenic environmental stimuli with arterial inflammation, oxidative stress, increased blood pressure and atherosclerosis. This is the first demonstration that inhibition of a single cytokine can block the rise in blood pressure in response to an environmental stimulus. IL-1 inhibition may have profound beneficial effects on atherogenesis in man