528 research outputs found

    A City in Common: A Framework to Orchestrate Large-scale Citizen Engagement around Urban Issues

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    Citizen sensing is an approach that develops and uses lightweight technologies with local communities to collect, share and act upon data. In doing so it enables them to become more aware of how they can tackle local issues. We report here on the development and uptake of the 'City- Commons Framework for Citizen Sensing', a conceptual model that builds on Participatory Action Research with the aim of playing an integrating role: outlining the processes and mechanisms for ensuring sensing technologies are co-designed by citizens to address their concerns. At the heart of the framework is the idea of a city commons: a pool of community-managed resources. We discuss how the framework was used by communities in Bristol to measure and monitor the problem of damp housing

    Cardiovascular magnetic resonance-guided right heart catheterization in a conventional CMR environment - predictors of procedure success and duration in pulmonary artery hypertension

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    Background Cardiovascular magnetic resonance imaging (CMR) is valuable for the investigation and management of pulmonary artery hypertension (PAH), but the direct measurement of pulmonary hemodynamics by right heart catheterization is still necessary. CMR-guided right heart catheterization (CMR-RHC) combines the benefits of CMR and invasive cardiac catheterization, but its feasibility in patients with acquired PAH has not been established. The aims of this study are to: (1) demonstrate the feasibility of CMR-RHC in patients being assessed for PAH in a conventional diagnostic CMR scanner room; (2) determine the predictors of (i) procedure duration, and (ii) procedural failure or technical difficulty as determined by the adjunctive need for a guidewire. Methods Fifty patients investigated for suspected or known PH underwent CMR-RHC. Durations of separate procedural components were recorded, including time taken to pass the catheter from the femoral vein to a stable wedge position (procedure time) and total time the patient spent in the CMR department (department time). Associations between procedural failure/guidewire usage and hemodynamic/CMR measures were assessed using logistic regression. Relationships between procedure times and hemodynamic/CMR measures were evaluated using Spearman’s correlation coefficient. Results A full CMR-RHC study was successfully completed in 47 (94%) patients. CMR-conditional guidewires were used in 6 (12%) patients. Metrics associated with guidewire use/procedural failure were higher mean pulmonary artery (PA) pressures (mPAP: OR = 1.125, p = 0.018), right heart dilatation (right ventricular (RV) end-systolic volume (RVESV): OR = 1.028, p = 0.018), RV hypertrophy (OR = 1.050, p = 0.0067) and RV ejection fraction (EF) (OR = 0.914, p = 0.014). Median catheter and department times were 3.6 (2.0–7.7) minutes and 60.0 (54.0–68.5) minutes, respectively. All procedure times became significantly shorter with increasing procedural experience (p < 0.05). Catheterization time was also associated with PH severity (RV systolic pressure: rho = 0.46, p = 0.0013) and increasing RV end-systolic volume (RVESV: rho = 0.41, p = 0.0043), hypertrophy (rho = 0.43, p = 0.0025) and dysfunction (RVEF: rho = − 0.32, p = 0.031). Conclusions This study demonstrates that CMR-RHC using standard technology can be incorporated into routine clinical practice for the investigation of PAH. Procedural failure was rare but more likely in patients with severe PAH. Procedure time is clinically acceptable and increases with worsening PAH severity

    Reduced exercise capacity in patients with systemic sclerosis is associated with lower peak tissue oxygen extraction: a cardiovascular magnetic resonance-augmented cardiopulmonary exercise study

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    Background: Exercise intolerance in systemic sclerosis (SSc) is typically attributed to cardiopulmonary limitations. However, problems with skeletal muscle oxygen extraction have not been fully investigated. This study used cardiovascular magnetic resonance (CMR)-augmented cardiopulmonary exercise testing (CMR-CPET) to simultaneously measure oxygen consumption and cardiac output. This allowed calculation of arteriovenous oxygen content gradient, a recognized marker of oxygen extraction. We performed CMR-CPET in 4 groups: systemic sclerosis (SSc); systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH); non-connective tissue disease pulmonary hypertension (NC-PAH); and healthy controls. Methods: We performed CMR-CPET in 60 subjects (15 in each group) using a supine ergometer following a ramped exercise protocol until exhaustion. Values for oxygen consumption, cardiac output and oxygen content gradient, as well as ventricular volumes, were obtained at rest and peak-exercise for all subjects. In addition, T1 and T2 maps were acquired at rest, and the most recent clinical measures (hemoglobin, lung function, 6-min walk, cardiac and catheterization) were collected. Results: All patient groups had reduced peak oxygen consumption compared to healthy controls (p<0.022). The SSc and SSc-PAH groups had reduced peak oxygen content gradient compared to healthy controls (p<0.03). Conversely, the SSc-PAH and NC-PH patients had reduced peak cardiac output compared to healthy controls and SSc patients (p<0.006). Higher hemoglobin was associated with higher peak oxygen content gradient (p=0.025) and higher myocardial T1 was associated with lower peak stroke volume (p=0.011). Conclusions: Reduced peak oxygen consumption in SSc patients is predominantly driven by reduced oxygen content gradient and in SSc-PAH patients this was amplifed by reduced peak cardiac output

    On the statistical mechanics of prion diseases

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    We simulate a two-dimensional, lattice based, protein-level statistical mechanical model for prion diseases (e.g., Mad Cow disease) with concommitant prion protein misfolding and aggregation. Our simulations lead us to the hypothesis that the observed broad incubation time distribution in epidemiological data reflect fluctuation dominated growth seeded by a few nanometer scale aggregates, while much narrower incubation time distributions for innoculated lab animals arise from statistical self averaging. We model `species barriers' to prion infection and assess a related treatment protocol.Comment: 5 Pages, 3 eps figures (submitted to Physical Review Letters

    Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans

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    The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes

    Long-Term Survival, Safety and Tolerability with Selexipag in Patients with Pulmonary Arterial Hypertension: Results from GRIPHON and its Open-Label Extension

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    INTRODUCTION: In the event-driven GRIPHON randomised-controlled trial, the oral prostacyclin receptor agonist selexipag significantly reduced the risk of disease progression (composite primary endpoint of morbidity/mortality), compared with placebo, in patients with pulmonary arterial hypertension (PAH). The ongoing open-label extension study (GRIPHON OL) collects further data on long-term safety, tolerability, and survival of PAH patients treated with selexipag. METHODS: Patients randomised to selexipag or placebo in GRIPHON could enter GRIPHON OL either after experiencing a morbidity event during double-blind treatment or at the end of the study. Patients were followed for adverse events (AE) and survival from selexipag initiation up to 3&nbsp;days and 30&nbsp;days after end of treatment, respectively. Data are presented up to a cut-off date of 1 September 2019. RESULTS: Overall, 953 patients in GRIPHON and GRIPHON OL were treated with selexipag. At the time of selexipag initiation, 81.2% of patients were receiving background PAH therapy. Median (min, max) exposure to selexipag was 31.7&nbsp;months (0, 106), corresponding to a total of 3054.4 patient-years. The most frequently reported AEs were related to known prostacyclin-related effects or underlying disease. There were 305 (32.0%) patients who experienced an AE leading to treatment discontinuation. Survival during GRIPHON and GRIPHON OL was assessed for the 574 patients randomised to selexipag in GRIPHON. Kaplan-Meier survival estimates (95%CI) at 1, 3, 5 and 7&nbsp;years were 92.0% (89.4, 94.0), 79.3% (75.4, 82.6), 71.2% (66.5, 75.3) and 63.0% (57.4, 68.1), respectively. CONCLUSIONS: These results provide the longest follow-up period published to date for a PAH therapy. The safety profile of selexipag over this extended treatment period was consistent with that observed in GRIPHON. A large proportion of the population was receiving background therapy at selexipag initiation, providing further insight into the long-term safety of selexipag as part of a combination therapy regimen. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT01106014 and NCT01112306

    The challenge of enterprise/innovation: a case study of a modern university

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    In the prevailing economic and political climate for Higher Education a greater emphasis has been placed on diversifying the funding base. The present study was undertaken between 2012 and 2014 and addressed the implementation of an approach to the transformation of one academic school in a medium-sized modern university in Wales to a more engaged enterprise culture. A multimethod investigation included a bi-lingual (English and Welsh) online survey of academic staff and yielded a 71% response rate (n = 45). The findings informed a series of in-depth interviews (n = 24) with a representative sample of those involved in enterprise work (support staff, managers, senior managers), and those who were not. The results provided the platform for the ‘S4E model’ for effective engagement with enterprise: (1) Strategic significance for Enterprise, (2) Support for Enterprise, (3) Synergy for Enterprise, and (4) Success for Enterprise. The outcomes of the research and the recommendations from it have potential to inform practice in other academic schools within the university and, in a wider context, within other Schools of Education regionally, nationally and internationally. Its original empirical exploration of enterprise within education studies is a significant contribution to that body of knowledge

    Left ventricle remodelling by double-patch sandwich technique

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    BACKGROUND: The sandwich double-patch technique was adopted as an alternative method for reconstruction of the left ventricle after excision of postinfarction dysfunctional myocardium to solve technical problems due to the thick edges of the ventricular wall. METHODS: Over a 5-year period, 12 of 21 patients with postinfarction antero-apical left ventricular aneurysm had thick wall edges after wall excision. It was due to akinetic muscular thick tissue in 6 cases, while in the other 6 with classic fibrous aneurysm, thick edges remained after the cut of the border zone. The ventricular opening was sandwiched between two patches and this is a technique which is currently used for the treatment of the interventricular septum rupture. In our patients the patches are much smaller than the removed aneurysm and they were sutured simply by a single row of single stitches. However, in contrast to interventricular septum rupture where the patches loosen the tension of the tissues, in our patients the patches pull strongly and restrain the walls by fastening their edges and supporting tight stitches. In this way they could narrow the cavity and close the ventricle. RESULTS: The resected area varied from 5 × 4 to 8 × 8 cm. Excision was extended into the interventricular septum in 5 patients, thus opening the right ventricle. CABG was performed on all patients but two. Left ventricular volumes and the ejection fraction changed significantly: end-systolic volume 93.5 ± 12.4 to 57.8 ± 8.9 ml, p < 0.001; end-diastolic volume 157.2 ± 16.7 to 115.3 ± 14.9 ml, p < 0.001; ejection fraction 40.3 ± 4.2 to 49.5 ± 5.7%, p < 0.001. All patients did well. One patient suffered from bleeding, which was not from the wall suture, and another had a left arm paresis. The post-operative hospital stay was 5 to 30 days with a mean 10.5 ± 7.5 days/patient. At follow-up, 9 to 60 months mean 34, all patients were symptom-free. NYHA class 2.5 ± 0.8 changed to 1.2 ± 0.4, p < 0.001. CONCLUSION: The double-patch sandwich technique (bi-patch closure) offers some advantages and does not result in increased morbidity and mortality. In the case of excising a left ventricular aneurysm, this technique in no way requires eversion of the edges, felt strips, buttressed and multiple sutures, all of which are needed for longitudinal linear closure. Moreover, it does not require purse string sutures, endocardial scar remnant to secure the patch or folding the excluded non-functional tissue, all of which are needed for endoventricular patch repair

    Knowledge and malaria treatment practices using artemisinin combination therapy (ACT) in Malawi: survey of health professionals

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    <p>Abstract</p> <p>Background</p> <p>Malaria still remains a life-threatening disease worldwide causing between 190 and 311 million cases of malaria in 2008. Due to increased resistance to sulphadoxine-pyrimethamine (SP), the Ministry of Health in Malawi, as in many sub-Saharan African countries, changed the malaria treatment policy to use artemisinin-based combination therapy (ACT). In order to optimize the correct use of this drug, and protect against the development of the parasite's resistance, it is important to assess the knowledge and practices of medical practitioners on the use of ACT and its impact on adherence to new treatment policy guidelines.</p> <p>Methods</p> <p>A cross-sectional survey was conducted to assess the knowledge and perceptions of Malawian medical doctors and pharmacists on the use of ACT and the drivers of treatment choice and clinical treatment decisions. Medical doctors and pharmacists who are involved in managing malaria patients in Malawi were recruited and a self-administered questionnaire was used to obtain information on socio-demographic characteristics of the study participants, knowledge on ACT, source of information on ACT and methods used to decide on the treatment of patients with malaria.</p> <p>Results</p> <p>Most of the participants (95.7%) know at least one form of ACT, 67.4% reported that different forms of ACT have different characteristics, 77.3% reported that there are special formulations for children. The most commonly mentioned ACT was artemether-lumefantrine (AL), by 94.6% of the participants and 75.0% of the participants indicated that they prefer to prescribe AL. 73.9% of participants had ever received information on ACT. However, only 31.5% had received training on management of malaria using ACT. There were 71.7% respondents who had heard of ACT causing side effects. Only 25.0% of the participants had received training on how to report SAEs.</p> <p>Conclusion</p> <p>It was found that most of the participants know about ACT and treatment guidelines for malaria. However, most of the participants have not received any training on how to use ACT and how to report adverse effects arising from the use of ACT. There is need for more training of health care professionals to ensure correct and effective use of ACT.</p

    A conceptual model for action and design research

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    Organizational research has a pattern of special characteristics which make a clear distinction from other research paradigms. When using these approaches – based on Action and Design – the Interpretivist, Constructivist, and Participatory perspectives dominate. They have already proven to have strong foundations, which turn these paradigmatic approaches into effective ways for getting knowledge, doing things, and promoting change within organizational settings. It combines the traditional scientific, engineering, and organization development approaches, depicting how an organization can, simultaneously, solve multidimensional problems and produce actionable knowledge, effective change and useful artifacts. It has been developed using a Design Science Research approach, tested in a major organizational change program (Henriques, 2015; Henriques & ONeill, 2014), and successfully used to teach research methods essentials to Master and DBA students.info:eu-repo/semantics/publishedVersio
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