SPIRIT and CONSORT extensions for early phase dose-finding clinical trials:the DEFINE (DosE FIndiNg Extensions) study protocol

Introduction Early phase dose-finding (EPDF) studies are critical for the development of new treatments, directly influencing whether compounds or interventions can be investigated in further trials to confirm their safety and efficacy. There exists guidance for clinical trial protocols and reporting of completed trials in the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 and CONsolidated Standards Of Reporting Randomised Trials (CONSORT) 2010 statements. However, neither the original statements nor their extensions adequately cover the specific features of EPDF trials. The DEFINE (DosE-FIndiNg Extensions) study aims to enhance transparency, completeness, reproducibility and interpretation of EPDF trial protocols (SPIRIT-DEFINE) and their reports once completed (CONSORT-DEFINE), across all disease areas, building on the original SPIRIT 2013 and CONSORT 2010 statements. Methods and analysis A methodological review of published EPDF trials will be conducted to identify features and deficiencies in reporting and inform the initial generation of the candidate items. The early draft checklists will be enriched through a review of published and grey literature, real-world examples analysis, citation and reference searches and consultation with international experts, including regulators and journal editors. Development of CONSORT-DEFINE commenced in March 2021, followed by SPIRIT-DEFINE from January 2022. A modified Delphi process, involving worldwide, multidisciplinary and cross-sector key stakeholders, will be run to refine the checklists. An international consensus meeting in autumn 2022 will finalise the list of items to be included in both guidance extensions. Ethics and dissemination This project was approved by ICR’s Committee for Clinical Research. The Health Research Authority confirmed Research Ethics Approval is not required. The dissemination strategy aims to maximise guideline awareness and uptake, including but not limited to dissemination in stakeholder meetings, conferences, peer-reviewed publications and on the EQUATOR Network and DEFINE study websites

Does vegetation affect the methane oxidation efficiency of passive biosystems?

Abstract: It is often reported in the technical literature that the presence of vegetation improves the methane oxidation efficiency of biosystems; however, the phenomena involved and biosystem performance results are still poorly documented, particularly in the field. This triggered a study to assess the importance of vegetation in methane oxidation efficiency (MOE). In this study, 4 large scale columns, each filled with sand, topsoil and a mixture of compost and topsoil were tested under controlled conditions in the laboratory and partially controlled conditions in the field. Four series of laboratory tests and two series of field tests were performed. 4 different plant covers were tested for each series: Trifolium repens L. (White clover), Phleum pratense L. (Timothy grass), a mixture of both, and bare soil as the control biosystem. The study results indicated that up to a loading equal to 100 g CH4/m2/d, the type of plant cover did not influence the oxidation rates, and the MOE was quite high (⩾95%) in all columns. Beyond this point, the oxidation rate continued to increase, reaching 253 and 179 g CH4/m2/d in laboratory and field tests respectively. In the end, the bare soil achieved as high or higher MOEs than vegetated biosystems. Despite the fact that the findings of this study cannot be generalized to other types of biosystems and plants and that the vegetation types tested were not fully grown, it was shown that for the short-term tests performed and the types of substrates and plants used herein, vegetation does not seem to be a key factor for enhancing biosystem performance. This key conclusion does not corroborate the conclusion of the relatively few studies published in the technical literature assessing the importance of vegetation in MOE

Rare missense variants in Tropomyosin-4 (TPM4) are associated with platelet dysfunction, cytoskeletal defects, and excessive bleeding

Background: A significant challenge is faced for the genetic diagnosis of inherited platelet disorders in which candidate genetic variants can be found in more than 100 bleeding, thrombotic, and platelet disorder genes, especially within families in which there are both normal and low platelet counts. Genetic variants of unknown clinical significance (VUS) are found in a significant proportion of such patients in which functional studies are required to prove pathogenicity. Objective: To identify the genetic cause in patients with a suspected platelet disorder and subsequently perform a detailed functional analysis of the candidate genetic variants found. Methods: Genetic and functional studies were undertaken in three patients in two unrelated families with a suspected platelet disorder and excessive bleeding. A targeted gene panel of previously known bleeding and platelet genes was used to identify plausible genetic variants. Deep platelet phenotyping was performed using platelet spreading analysis, transmission electron microscopy, immunofluorescence, and platelet function testing using lumiaggregometry and flow cytometry. Results: We report rare conserved missense variants (p.R182C and p.A183V) in TPM4 encoding tromomyosin-4 in 3 patients. Deep platelet phenotyping studies revealed similar platelet function defects across the 3 patients including reduced platelet secretion, and aggregation and spreading defects suggesting that TPM4 missense variants impact platelet function and show a disordered pattern of tropomyosin staining. Conclusions: Genetic and functional TPM4 defects are reported making TPM4 a diagnostic grade tier 1 gene and highlights the importance of including TPM4 in diagnostic genetic screening for patients with significant bleeding and undiagnosed platelet disorders, particularly for those with a normal platelet count

How young adults in London experience the Clubhouse Model of mental health recovery: a thematic analysis

Clubhouses are recovery orientated, participatory communities in which people with mental health diagnoses can take part in the running of the clubhouse. The objective of this research was to produce the first qualitative study of its kind, examining how the clubhouse model of mental health recovery is perceived and experienced by young adults aged 16-25. Five participants provided lengthy and detailed semi-structured interviews regarding their experiences as members of a clubhouse in London. Analysis produced themes including mixed age services as a distinct benefit, the benefits of getting involved in the work of the clubhouse, the mostly positive perception of the clubhouse compared with other mental health services, and the sense of personal change and social improvement experienced on becoming members of the clubhouse. While further research is needed, it was concluded that the clubhouse model was beneficial to all its young members, for reasons including its entirely collaborative and consultative process between staff and members, its humanitarian approach, its lack of rigid or inflexible time limits, and its reciprocal relationships, where members are expected to both provide and receive support

Weaving indigenous agricultural knowledge with formal education to enhance community food security : school competition as a pedagogical space in rural Anchetty, India

In communities from the remote rural regions of Anchetty, young learners’ informal learning experiences often come through interactions with local agriculture and the environment in which they and their families work and learn. These informal learning experiences are essential to what are otherwise called ‘indigenous knowledge systems’. For primary school students in Anchetty, the ways in which they engage in learning community-based agricultural knowledge are challenged by school-based formal education processes. Using a school competition as a pedagogical strategy for integrative space, this paper supports and explores the meaning and characteristics of indigenous agricultural knowledge (IAK)