70 research outputs found
Behavioral influences on driver crash risks in Ghana: A qualitative study of commercial passenger drivers
Objectives: While there is a growing body of literature on crash risks in the developed world, little is known about how well these models apply to motoring in developing countries, the context in which the majority of road traffic fatalities occur. This qualitative study explores factors perceived to influencinge crash risks for commercial drivers in Ghana.
Method: Twenty commercial drivers of varied ages and experience were sampled from 7 major lorry terminals in 3 regions (Greater Accra, Ashanti, and Volta) of Ghana. Data were collected through semi-structured interviews.
Results: The participants identified some issues that are shared with drivers in the developed world, though moderated by the Ghanaian context. These included working pressures (e.g., fatigued driving), speeding, distracted driving and inadequate vehicle maintenance. Other factors identified by the participants are infrequently less frequently considered in research addressing driving behavior in developed countries. These included aggressive competition over passengers and corruption (e.g., improper licensing practices) among others.
Conclusion: The findings have implications for building a research base to support the development of road safety policy and interventions in developing countries
Scoping and targeted reviews to support development of SPIRIT and CONSORT extensions for randomised controlled trials with surrogate primary endpoints: protocol
Introduction Using a surrogate endpoint as a substitute for a primary patient-relevant outcome enables randomised controlled trials (RCTs) to be conducted more efficiently, that is, with shorter time, smaller sample size and lower cost. However, there is currently no consensus-driven guideline for the reporting of RCTs using a surrogate endpoint as a primary outcome; therefore, we seek to develop SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) extensions to improve the design and reporting of these trials. As an initial step, scoping and targeted reviews will identify potential items for inclusion in the extensions and participants to contribute to a Delphi consensus process. Methods and analysis The scoping review will search and include literature reporting on the current understanding, limitations and guidance on using surrogate endpoints in trials. Relevant literature will be identified through: (1) bibliographic databases; (2) grey literature; (3) handsearching of reference lists and (4) solicitation from experts. Data from eligible records will be thematically analysed into potential items for inclusion in extensions. The targeted review will search for RCT reports and protocols published from 2017 to 2021 in six high impact general medical journals. Trial corresponding author contacts will be listed as potential participants for the Delphi exercise. Ethics and dissemination Ethical approval is not required. The reviews will support the development of SPIRIT and CONSORT extensions for reporting surrogate primary endpoints (surrogate endpoint as the primary outcome). The findings will be published in open-access publications. This review has been prospectively registered in the OSF Registration DOI: 10.17605/OSF.IO/WP3QH
Blood flow rate to the femur of extinct kangaroos implies a higher locomotor intensity compared to living hopping macropods
DATA AVAILABILITY:
All data supporting the findings of this study are available within the paper, Online Resource 1 and Online Resource 2.SUPPLEMENTARY MATERIAL 1 : Online Resource 1. Numbers and accession numbers of specimens.SUPPLEMENTARY MATERIAL 2 : Online Resource 2. Measurements of specimens.SUPPLEMENTARY MATERIAL 3 : Online Resource 3. Femur blood flow rate scaling among three extinct kangaroo groups.The stocky skeletons and post-cranial anatomy of many extinct kangaroos indicate that they might have engaged in varied locomotor behaviors, rather than bipedal hopping, as their primary mode of locomotion. This study investigates support for this idea by estimating femoral bone perfusion, which is a correlate of locomotor intensity, in extinct kangaroos compared to living hopping species. Femur blood flow rates can be estimated from the sizes of nutrient foramina on the femur shaft of living and extinct species, without preservation of soft tissue. Estimated femur blood flow rates among the extinct Macropus, Protemnodon and Sthenurinae (Sthenurus, Simosthenurus and Procoptodon) are not significantly different from one another but are significantly greater than in living hopping macropods after accounting for the effect of body mass, consistent with their purportedly different locomotor style. The giant sthenurines have more robust femora than extrapolated from data of living hopping macropods, possibly due to the larger sthenurines requiring relatively stronger leg bones to support their heavier body weights, especially if loaded onto a single limb during bipedal striding.Open Access funding enabled and organized by CAUL and its Member Institutions This study was supported by Australian Research Council.https://link.springer.com/journal/10914hj2024Anatomy and PhysiologyCentre for Wildlife ManagementNon
Modification of the Creator recombination system for proteomics applications â improved expression by addition of splice sites
BACKGROUND: Recombinational systems have been developed to rapidly shuttle Open Reading Frames (ORFs) into multiple expression vectors in order to analyze the large number of cDNAs available in the post-genomic era. In the Creator system, an ORF introduced into a donor vector can be transferred with Cre recombinase to a library of acceptor vectors optimized for different applications. Usability of the Creator system is impacted by the ability to easily manipulate DNA, the number of acceptor vectors for downstream applications, and the level of protein expression from Creator vectors. RESULTS: To date, we have developed over 20 novel acceptor vectors that employ a variety of promoters and epitope tags commonly employed for proteomics applications and gene function analysis. We also made several enhancements to the donor vectors including addition of different multiple cloning sites to allow shuttling from pre-existing vectors and introduction of the lacZ alpha reporter gene to allow for selection. Importantly, in order to ameliorate any effects on protein expression of the loxP site between a 5' tag and ORF, we introduced a splicing event into our expression vectors. The message produced from the resulting 'Creator Splice' vector undergoes splicing in mammalian systems to remove the loxP site. Upon analysis of our Creator Splice constructs, we discovered that protein expression levels were also significantly increased. CONCLUSION: The development of new donor and acceptor vectors has increased versatility during the cloning process and made this system compatible with a wider variety of downstream applications. The modifications introduced in our Creator Splice system were designed to remove extraneous sequences due to recombination but also aided in downstream analysis by increasing protein expression levels. As a result, we can now employ epitope tags that are detected less efficiently and reduce our assay scale to allow for higher throughput. The Creator Splice system appears to be an extremely useful tool for proteomics
Scoping and targeted reviews to support development of SPIRIT and CONSORT extensions for randomised controlled trials with surrogate primary endpoints: protocol
Introduction: Using a surrogate endpoint as a substitute for a primary patient-relevant outcome enables randomised controlled trials (RCTs) to be conducted more efficiently, that is, with shorter time, smaller sample size and lower cost. However, there is currently no consensus-driven guideline for the reporting of RCTs using a surrogate endpoint as a primary outcome; therefore, we seek to develop SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) extensions to improve the design and reporting of these trials. As an initial step, scoping and targeted reviews will identify potential items for inclusion in the extensions and participants to contribute to a Delphi consensus process.
Methods and analysis: The scoping review will search and include literature reporting on the current understanding, limitations and guidance on using surrogate endpoints in trials. Relevant literature will be identified through: (1) bibliographic databases; (2) grey literature; (3) handsearching of reference lists and (4) solicitation from experts. Data from eligible records will be thematically analysed into potential items for inclusion in extensions. The targeted review will search for RCT reports and protocols published from 2017 to 2021 in six high impact general medical journals. Trial corresponding author contacts will be listed as potential participants for the Delphi exercise.
Ethics and dissemination: Ethical approval is not required. The reviews will support the development of SPIRIT and CONSORT extensions for reporting surrogate primary endpoints (surrogate endpoint as the primary outcome). The findings will be published in open-access publications
Adaptation of complex interventions for people with long-term conditions: a scoping review
Adaptation seeks to transfer and implement healthcare interventions developed and evaluated in one context to another. The aim of this scoping review was to understand current approaches to the adaptation of complex interventions for people with long-term conditions (LTCs) and to identify issues for studies performed in low- and middle-income countries (LMICs). Bibliographic databases were searched from 2000 to October 2022. This review involved five stages: (i) definition of the research question(s); (ii) identifying relevant studies; (iii) study selection; (iv) data charting; and (v) data synthesis. Extraction included an assessment of the: rationale for adaptation; stages and levels of adaptation; use of theoretical frameworks, and quality of reporting using a checklist based on the 2021 ADAPT guidance. Twenty-five studies were included from across 21 LTCs and a range of complex interventions. The majority (16 studies) focused on macro (national or international) level interventions. The rationale for adaptation included intervention transfer across geographical settings [high-income country (HIC) to LMIC: six studies, one HIC to another: eight studies, one LMIC to another: two studies], or transfer across socio-economic/racial groups (five studies), or transfer between different health settings within a single country (one study). Overall, studies were judged to be of moderate reporting quality (median score 23, maximum 46), and typically focused on early stages of adaptation (identification and development) with limited outcome evaluation or implementation assessment of the adapted version of the intervention. Improved reporting of the adaptation for complex interventions targeted at LTCs is needed. Development of future adaptation methods guidance needs to consider the needs and priorities of the LMIC context
Definitions, acceptability, limitations, and guidance in the use and reporting of surrogate end points in trials: a scoping review
Objective
To synthesize the current literature on the use of surrogate end points, including definitions, acceptability, and limitations of surrogate end points and guidance for their design/reporting, into trial reporting items.
Study Design and Setting
Literature was identified through searching bibliographic databases (until March 1, 2022) and gray literature sources (until May 27, 2022). Data were thematically analyzed into four categories: (1) definitions, (2) acceptability, (3) limitations and challenges, and (4) guidance, and synthesized into reporting guidance items.
Results
After screening, 90 documents were included: 79% (n = 71) had data on definitions, 77% (n = 69) on acceptability, 72% (n = 65) on limitations and challenges, and 61% (n = 55) on guidance. Data were synthesized into 17 potential trial reporting items: explicit statements on the use of surrogate end point(s) and justification for their use (items 1â6); methodological considerations, including whether sample size calculations were informed by surrogate validity (items 7â9); reporting of results for composite outcomes containing a surrogate end point (item 10); discussion and interpretation of findings (items 11â14); plans for confirmatory studies, collecting data on the surrogate end point and target outcome, and data sharing (items 15â16); and informing trial participants about using surrogate end points (item 17).
Conclusion
The review identified and synthesized items on the use of surrogate end points in trials; these will inform the development of the Standard Protocol Items: Recommendations for Interventional TrialsâSURROGATE and Consolidated Standards of Reporting TrialsâSURROGATE extensions
Promiscuously Partisan? Public Service Impartiality and Responsiveness in Westminster Systems
Public servants in Westminster countries are being drawn into the limelight bydemands from their political masters that they publicly defend policies. Critics suggestthese conditions undermine the capacity and willingness of senior public servants tomanage the enduring Westminster tension between serving elected governments andremaining nonpartisan. Interviews with senior officials from Australia, Canada, andthe United Kingdom challenge this pessimistic view, showing that officials consistentlystress the importance of not âcrossing the lineâ when dealing with their elected masters.Two exploratory case studies are presentedâone of an Australian ministerialdepartment (Treasury) and another of a Canadian quasi-autonomous agency (StatisticsCanada)âin which public servants faced pressure to defend controversial governmentpolicies. These cases show how contemporary public servants actively interpret,establish, and defend the line between appropriate responsiveness and inappropriatepartisanship in Westminster systems
Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1
PMCID: PMC3601088This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Definitions, acceptability, limitations, and guidance in the use and reporting of surrogate endpoints in trials: a scoping review
Objective:
To synthesise the current literature on the use of surrogate endpoints, including definitions, acceptability, and limitations of surrogate endpoints, and guidance for their design/reporting, into trial reporting items.
Study Design and Setting:
Literature was identified through searching bibliographic databases (until March 1st, 2022) and grey literature sources (until May 27th, 2022). Data were thematically analysed into four categories: (1) definitions, (2) acceptability, (3) limitations and challenges, and (4) guidance, and synthesised into reporting guidance items.
Results:
After screening, 90 documents were included: 79% (n=71) had data on definitions, 77% (n=69) on acceptability, 72% (n=65) on limitations and challenges, and 61% (n=55) on guidance. Data were synthesised into 17 potential trial reporting items: explicit statements on the use of surrogate endpoint(s) and justification for their use (items 1-6); methodological considerations, including whether sample size calculations were informed by surrogate validity (items 7-9); reporting of results for composite outcomes containing a surrogate endpoint (item 10); discussion and interpretation of findings (items 11-14); plans for confirmatory studies, collecting data on the surrogate endpoint and target outcome, and data sharing (items 15-16); and informing trial participants about using surrogate endpoints (item 17).
Conclusion:
The review identified and synthesised items on the use of surrogate endpoints in trials; these will inform the development of the SPIRIT-SURROGATE and CONSORT-SURROGATE extensions
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