Takshan/R1 huggingface dataset:
What are the barriers and facilitators for third sector organisations (non-profits) to evaluate their services? A systematic review.

BACKGROUND: The third sector is becoming a more common provider of social and health services, but little is known about how third sector organisations (TSOs) evaluate their activities. Past research has reported that the third sector is under increasing pressure to evaluate its impact and performance by government and other commissioning bodies. However, in responding to this increased pressure to undertake evaluation, research suggests that many TSOs struggle to evaluate their activities following the principles of evidence-based practice (EBP). Yet, there has been no systematic effort to investigate why the third sector is struggling to provide good quality evidence of its effects. METHODS: This systematic review is reported following the PRISMA guidelines. Ten interdisciplinary databases were searched using a search string developed following best practice and in consultation with an information systems expert. Included studies were primary research of any research design investigating barriers to and facilitators of the evaluation process of TSOs as identified by practitioners. All studies were quality appraised, and the results were synthesised as a thematic summary. RESULTS: Twenty-four studies were included, which mainly investigated TSOs working within health and social services. The thematic summary identified the main barriers for TSOs to undertake evaluation to be related to the (1) lack of financial resources, (2) lack of technical capability and evaluation literacy and (3) challenges around identifying relevant evaluation systems and outcome indicators. Key facilitating factors involved (1) getting the appropriate support, (2) having an organisational culture that supports evaluation and (3) the motivation to be accountable to stakeholders. These findings were robust to study quality. CONCLUSIONS: This review constitutes the first systematic effort to synthesise existing literature on factors supporting and preventing evaluation by TSOs. The prevalence of factors revolving around the lack of support, resources and clarity on appropriate outcome indicators suggests that many of the identified challenges may be met by applying evidence-based and stakeholder-inclusive strategies to develop shared evaluation requirements. Future efforts should address the application of EBP as part of the commissioning process of TSOs.
(18)F-GP1, a Novel PET Tracer Designed for High-Sensitivity, Low-Background Detection of Thrombi.

Thromboembolic diseases such as myocardial infarction, stroke, transient ischemic attacks, and pulmonary embolism are major causes of morbidity and mortality worldwide. Glycoprotein IIb/IIIa (GPIIb/IIIa) is the key receptor involved in platelet aggregation and is a validated target for therapeutic approaches and diagnostic imaging. The aim of this study was to develop and characterize a specific small-molecule tracer for PET imaging that binds with high affinity to GPIIb/IIIa receptors and has suitable pharmacokinetic properties to overcome limitations of previous approaches. Methods: Binding of (18)F-GP1 to GPIIb/IIIa receptors was investigated in competition binding assays and autoradiography using a fresh cardiac thrombus from an explanted human heart. The clot-to-blood ratio for (18)F-GP1 was investigated by an in vitro blood flow model. Biodistribution and thrombus detection was investigated in cynomolgus monkeys after insertion of a roughened catheter into either the vena cava or the aorta. Results:(18)F-GP1 is an (18)F-labeled small molecule for PET imaging of thrombi. The half maximal inhibitory concentration of (18)F-GP1 to GPIIb/IIIa was 20 nM. (18)F-GP1 bound to thrombi with a mean clot-to-blood ratio of 95. Binding was specific and can be displaced by excess nonradioactive derivative. Binding was not affected by anticoagulants such as aspirin or heparin. (18)F-GP1 showed rapid blood clearance and a low background after intravenous injection in cynomolgus monkeys. Small arterial, venous thrombi, thrombotic depositions on damaged endothelial surface, and small cerebral emboli were detected in vivo by PET imaging. Conclusions:(18)F-GP1 binds specifically with high affinity to the GPIIb/IIIa receptor involved in platelet aggregation. Because of its favorable preclinical characteristics, (18)F-GP1 is currently being investigated in a human clinical study.
Pharmacists' role in harm reduction: a survey assessment of Kentucky community pharmacists' willingness to participate in syringe/needle exchange.

BACKGROUND: Pharmacists' role in harm reduction is expanding in many states, yet there are limited data on pharmacists' willingness to participate in harm reduction activities. This study assessed community pharmacists' willingness to participate in one harm reduction initiative: syringe/needle exchange. METHODS: In 2015, all Kentucky pharmacists with active licenses were emailed a survey that examined attitudes towards participation in syringe/needle exchange. Response frequencies were calculated for community pharmacist respondents. Ordinal logistic regression estimated the impact of community pharmacist characteristics and attitudes on willingness to provide clean needles/syringes to people who inject drugs and to dispose of used syringes/needles, where both dependent variables were defined as Likert-type questions on a scale of 1 (not at all willing) to 6 (very willing). RESULTS: Of 4699 practicing Kentucky pharmacists, 1282 pharmacists responded (response rate = 27.3%); the majority (n = 827) were community pharmacists. Community pharmacists were divided on willingness to provide clean needles/syringes, with 39.1% not willing (score 1 or 2 of 6) and 30% very willing (score 5 or 6 of 6). Few were willing to dispose of used needles/syringes, with only 18.7% willing. Community pharmacists who agreed that pharmacists could have significant public health impact by providing access to clean needles expressed 3.56 times more willingness to provide clean needles (95% CI 3.06-4.15), and 2.04 times more willingness to dispose of used needles (95% CI 1.77-2.35). Chain/supermarket pharmacists (n = 485, 58.6% of community pharmacies) were 39% less likely to express willingness to dispose of used needles (95% CI 0.43-0.87) when compared with independent community pharmacists (n = 342, 41.4% of community pharmacies). Independent pharmacists reported different barriers (workflow) than their chain/supermarket pharmacist colleagues (concerns of clientele). CONCLUSIONS: Kentucky community pharmacists were more willing to provide clean needles than to dispose of used needles. Strategies to mitigate barriers to participation in syringe/needle exchange are warranted.
GenIO: a phenotype-genotype analysis web server for clinical genomics of rare diseases.

BACKGROUND: GenIO is a novel web-server, designed to assist clinical genomics researchers and medical doctors in the diagnostic process of rare genetic diseases. The tool identifies the most probable variants causing a rare disease, using the genomic and clinical information provided by a medical practitioner. Variants identified in a whole-genome, whole-exome or target sequencing studies are annotated, classified and filtered by clinical significance. Candidate genes associated with the patient's symptoms, suspected disease and complementary findings are identified to obtain a small manageable number of the most probable recessive and dominant candidate gene variants associated with the rare disease case. Additionally, following the American College of Medical Genetics and Genomics and the Association of Molecular Pathology (ACMG-AMP) guidelines and recommendations, all potentially pathogenic variants that might be contributing to disease and secondary findings are identified. RESULTS: A retrospective study was performed on 40 patients with a diagnostic rate of 40%. All the known genes that were previously considered as disease causing were correctly identified in the final inherit model output lists. In previously undiagnosed cases, we had no additional yield. CONCLUSION: This unique, intuitive and user-friendly tool to assists medical doctors in the clinical genomics diagnostic process is openly available at https://bioinformatics.ibioba-mpsp-conicet.gov.ar/GenIO/ .
[Anopheles cruzii parity in dense rain forest in Southern Brazil].

Paridade de Anopheles cruzii em Floresta Ombrófila Densa no Sul do Brasil. OBJECTIVE: To determine the parity and ovarian development of Anopheles cruzii species during the seasons. METHODS: Collections were carried out fortnightly in the morning in the Palmito State Park in the municipality of Paranaguá, Southern Brazil, between April 2004 and April 2005. Adult mosquitoes were captured using human landing rate. Dissections were performed using Detinova's and Polovodova's methods and follicular development was assessed following Christophers and Mer's criteria. RESULTS: A total of 208 specimens of Anopheles cruzii were dissected. Most females dissected were nulliparous in the seasons; 14.4% of them were found to be nulliparous above Christophers and Mer's stage II, which shows previous blood meal prior to the first oviposition. It was observed that Anopheles cruzii populations comprised young mosquitoes, probably due to high mortality among parous females. CONCLUSIONS: The likely gonotrophic discordance is epidemiologically relevant because female mosquitoes can search for more than one host to complete the maturation of their eggs.
Cell migration analysis: A low-cost laboratory experiment for cell and developmental biology courses using keratocytes from fish scales.

Cell and developmental processes are complex, and profoundly dependent on spatial relationships that change over time. Innovative educational or teaching strategies are always needed to foster deep comprehension of these processes and their dynamic features. However, laboratory exercises in cell and developmental biology at the undergraduate level do not often take into account the time dimension. In this article, we provide a laboratory exercise focused in cell migration, aiming to stimulate thinking in time and space dimensions through a simplification of more complex processes occurring in cell or developmental biology. The use of open-source tools for the analysis, as well as the whole package of raw results (available at http://github.com/danielprieto/keratocyte) make it suitable for its implementation in courses with very diverse budgets. Aiming to facilitate the student's transition from science-students to science-practitioners we propose an exercise of scientific thinking, and an evaluation method. This in turn is communicated here to facilitate the finding of common caveats and weaknesses in the process of producing simple scientific communications describing the results achieved. © 2017 by The International Union of Biochemistry and Molecular Biology, 2017.
Consumer/patient encounters with prescription drug monitoring programs: evidence from a Medicaid population.

BACKGROUND: Prescription drug monitoring programs issue reports about a patient's controlled substance prescription history upon request to physicians, law enforcement officials, and pharmacists. The dual purposes of these programs are to reduce the abuse and diversion of controlled substances while not preventing access to these medications for legitimate medical need. OBJECTIVE: The purpose of this study was to examine the experiences of Medicaid patients with Kentucky's Prescription Drug Monitoring Program (PDMP). STUDY DESIGN: A random sample of Medicaid patients was surveyed in 2010; respondents were matched with patient retrospective claims data from 6 months prior to the survey's administration. SETTING: Kentucky Medicaid patients from across the state. METHODS: A combination of patient surveys and Medicaid claims data was used to test the relationship between patient characteristics and patient-reported interactions with physicians regarding their PDMP reports and whether they experienced difficulty obtaining or filling a prescription for a controlled substance due to a PDMP report. RESULTS: Most Medicaid patients are unaffected by the PDMP; however, patients diagnosed with chronic non-cancer pain conditions and patients reporting a Hispanic ethnicity are significantly more likely to have a physician discuss their PDMP report with them. Patients diagnosed with chronic non-cancer pain conditions are also significantly more likely to report difficulty obtaining a prescription for a controlled substance than patients that have not been diagnosed with chronic non-cancer pain conditions. Patients living in rural areas are significantly less likely than patients in urban areas to report difficulty obtaining a prescription for a controlled substance. LIMITATIONS: The utilization of controlled substance prescriptions by respondents was not measured or monitored. The Medicaid population examined in this study may not be representative of the population as a whole. CONCLUSIONS: These results suggest that more attention to the consumer/patient perspective is warranted in maintaining a balanced approach to decreasing drug abuse and diversion while not limiting access to controlled substances in cases of legitimate medical need.
Prognostic impact of anastomotic leakage after elective colon resection for cancer - A propensity score matched analysis of 628 patients.

BACKGROUND: There is limited information regarding the impact of anastomotic leakage on oncologic outcome in exclusively colon cancer patients. METHODS: The colorectal database of the Department of Surgery of the University of Heidelberg was used to assess the impact of anastomotic leakage on oncologic outcome in patients undergoing curative resection for Stage I-III colon cancer. Risk-adjusted Cox regression analysis and propensity score methods were used to assess overall, disease-free, and relative survival. RESULTS: 628 patients of which 26 (4.1%) experienced anastomotic leakage were analysed. Anastomotic leakage was associated with significantly worse overall, disease-free and relative survival in univariate and multivariate analysis. The analysis after exact propensity score matching confirmed the negative impact of anastomotic leakage on overall (HR 2.62, 95% CI 1.33-5.18, p = .011), disease-free (HR 2.28, 95% CI 1.16-4.47, p = .027) and relative survival (HR 3.70, 95% CI 1.82-7.52, p < .001). 5-year overall survival was 51.6% (95% CI 34.5-77.2%) for patients with anastomotic leakage compared to 77.7% (95% CI 73.0-82.8%) for patients without anastomotic leakage. CONCLUSIONS: All conceivable efforts should be made to avoid anastomotic leakage after colon resection for cancer not only to evade short-term consequences but also to allow for adequate long-term outcome.
Partial pancreatoduodenectomy versus duodenum-preserving pancreatic head resection in chronic pancreatitis: the multicentre, randomised, controlled, double-blind ChroPac trial.

BACKGROUND: There is substantial uncertainty regarding the optimal surgical treatment for chronic pancreatitis. Short-term outcomes have been found to be better after duodenum-preserving pancreatic head resection (DPPHR) than after partial pancreatoduodenectomy. Therefore, we designed the multicentre ChroPac trial to investigate the long-term outcomes of patients with chronic pancreatitis within 24 months after surgery. METHODS: This randomised, controlled, double-blind, parallel-group, superiority trial was done in 18 hospitals across Europe. Patients with chronic pancreatitis who were planned for elective surgical treatment were randomly assigned to DPPHR or partial pancreatoduodenectomy with a central web-based randomisation tool. The primary endpoint was mean quality of life within 24 months after surgery, measured with the physical functioning scale of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Primary analysis included all patients who underwent one of the assigned procedures; safety analysis included all patients who underwent surgical intervention (categorised into groups as treated). Patients and outcome assessors were masked to group assignment. The trial was registered, ISRCTN38973832. Recruitment was completed on Sept 3, 2013. FINDINGS: Between Sept 10, 2009, and Sept 3, 2013, 250 patients were randomly assigned to DPPHR (n=125) or partial pancreatoduodenectomy (n=125), of whom 226 patients (115 in the DPPHR group and 111 in the partial pancreatoduodenectomy group) were analysed. No difference in quality of life was seen between the groups within 24 months after surgery (75·3 [SD 16·4] for partial pancreatoduodenectomy vs 73·0 [16·4] for DPPHR; mean difference -2·3, 95% CI -6·6 to 2·0; p=0·284). The incidence and severity of serious adverse events did not differ between the groups. 70 (64%) of 109 patients in the DPPHR group and 61 (52%) of 117 patients in the partial pancreatoduodenectomy group had at least one serious adverse event, with the most common being reoperations (for reasons other than chronic pancreatitis), gastrointestinal problems, and other surgical morbidity. INTERPRETATION: No differences in quality of life after surgery for chronic pancreatitis were seen between the interventions. Results from single-centre trials showing superiority for DPPHR were not confirmed in the multicentre setting. FUNDING: German Research Foundation (DFG).
Meta-analysis of prophylactic abdominal drainage in pancreatic surgery.

BACKGROUND: Intra-abdominal drains are frequently used after pancreatic surgery whereas their benefit in other gastrointestinal operations has been questioned. The objective of this meta-analysis was to compare abdominal drainage with no drainage after pancreatic surgery. METHODS: PubMed, the Cochrane Library and Web of Science electronic databases were searched systematically to identify RCTs comparing abdominal drainage with no drainage after pancreatic surgery. Two independent reviewers critically appraised the studies and extracted data. Meta-analyses were performed using a random-effects model. Odds ratios (ORs) were calculated to aggregate dichotomous outcomes, and weighted mean differences for continuous outcomes. Summary effect measures were presented together with their 95 per cent confidence intervals. RESULTS: Some 711 patients from three RCTs were included. The 30-day mortality rate was 2·0 per cent in the drain group versus 3·4 per cent after no drainage (OR 0·68, 95 per cent c.i. 0·26 to 1·79; P = 0·43). The morbidity rate was 65·6 per cent in the drain group and 62·0 per cent in the no-drain group (OR 1·17, 0·86 to 1·60; P = 0·31). Clinically relevant pancreatic fistulas were seen in 11·5 per cent of patients in the drain group and 9·5 per cent in the no-drain group. Reinterventions, intra-abdominal abscesses and duration of hospital stay also showed no significant difference between the two groups. CONCLUSION: Pancreatic resection with, or without abdominal drainage results in similar rates of mortality, morbidity and reintervention.
Phylogeographic diversity and mosaicism of the Helicobacter pylori tfs integrative and conjugative elements.

Background: The genome of the gastric pathogen Helicobacter pylori is characterised by considerable variation of both gene sequence and content, much of which is contained within three large genomic islands comprising the cag pathogenicity island (cagPAI) and two mobile integrative and conjugative elements (ICEs) termed tfs3 and tfs4. All three islands are implicated as virulence factors, although whereas the cagPAI is well characterised, understanding of how the tfs elements influence H. pylori interactions with different human hosts is significantly confounded by limited definition of their distribution, diversity and structural representation in the global H. pylori population. Results: To gain a global perspective of tfs ICE population dynamics we established a bioinformatics workflow to extract and precisely define the full tfs pan-gene content contained within a global collection of 221 draft and complete H. pylori genome sequences. Complete (ca. 35-55kbp) and remnant tfs ICE clusters were reconstructed from a dataset comprising > 12,000 genes, from which orthologous gene complements and distinct alleles descriptive of different tfs ICE types were defined and classified in comparative analyses. The genetic variation within defined ICE modular segments was subsequently used to provide a complete description of tfs ICE diversity and a comprehensive assessment of their phylogeographic context. Our further examination of the apparent ICE modular types identified an ancient and complex history of ICE residence, mobility and interaction within particular H. pylori phylogeographic lineages and further, provided evidence of both contemporary inter-lineage and inter-species ICE transfer and displacement. Conclusions: Our collective results establish a clear view of tfs ICE diversity and phylogeographic representation in the global H. pylori population, and provide a robust contextual framework for elucidating the functional role of the tfs ICEs particularly as it relates to the risk of gastric disease associated with different tfs ICE genotypes.
Guidance for using pilot studies to inform the design of intervention trials with continuous outcomes.

Background: A pilot study can be an important step in the assessment of an intervention by providing information to design the future definitive trial. Pilot studies can be used to estimate the recruitment and retention rates and population variance and to provide preliminary evidence of efficacy potential. However, estimation is poor because pilot studies are small, so sensitivity analyses for the main trial's sample size calculations should be undertaken. Methods: We demonstrate how to carry out easy-to-perform sensitivity analysis for designing trials based on pilot data using an example. Furthermore, we introduce rules of thumb for the size of the pilot study so that the overall sample size, for both pilot and main trials, is minimized. Results: The example illustrates how sample size estimates for the main trial can alter dramatically by plausibly varying assumptions. Required sample size for 90% power varied from 392 to 692 depending on assumptions. Some scenarios were not feasible based on the pilot study recruitment and retention rates. Conclusion: Pilot studies can be used to help design the main trial, but caution should be exercised. We recommend the use of sensitivity analyses to assess the robustness of the design assumptions for a main trial.