Reporting Of Results In Clinicaltrials.gov And High-Impact Journals: A Cross-Sectional Study

In 2007, the FDA Amendments Act expanded requirements for ClinicalTrials.gov, a public clinical trial registry maintained by the U.S. National Library of Medicine, mandating results reporting within 12 months of trial completion for all FDA regulated drugs. We compared clinical trial results reported on ClinicalTrials.gov with corresponding published articles. We conducted a cross-sectional analysis of clinical trials published from July 1, 2010 through June 30, 2011 in high impact journals (impact factor 10 or higher) that were registered and reported results on ClinicalTrials.gov. We compared trial results reported on ClinicalTrials.gov and within published articles for the following: cohort characteristics, trial intervention, primary and secondary efficacy endpoint definition(s) and results, and adverse events. Of 95 included clinical trials registered and reporting results on ClinicalTrials.gov, there were 96 corresponding publications, among which 95 (99%) had at least one discrepancy in reporting of trial details, efficacy results, or adverse events between the two sources. When comparing reporting of primary efficacy endpoints, 132 (85%) were described in both sources, 14 (9%) were described only on ClinicalTrials.gov, and 10 (6%) only within articles. Results for 30 of 132 (23%) primary endpoints could not be compared because of reporting differences between the two sources (e.g., tabular versus graphics); among the remaining 102, reported results were discordant for 21 (21%), altering interpretations for 6 (6%). When comparing reporting of secondary endpoints, 619 (30%) were described in both sources, 421 (20%) were described only on ClinicalTrials.gov, and 1049 (50%) only within articles. Results for 228 of 619 (37%) secondary endpoints could not be compared; among the remaining 391, reported results were discordant for 53 (14%). Among published clinical trials that were registered and reported results on ClinicalTrials.gov, nearly all had at least one discrepancy in reported results, including a fifth among primary endpoints. Our findings question the accuracy of both sources and raise concerns about the usefulness of results reporting to inform clinical practice and future research efforts

Discerning the spatio-temporal disease patterns of surgically induced OA mouse models

Osteoarthritis (OA) is the most common cause of disability in ageing societies, with no effective therapies available to date. Two preclinical models are widely used to validate novel OA interventions (MCL-MM and DMM). Our aim is to discern disease dynamics in these models to provide a clear timeline in which various pathological changes occur. OA was surgically induced in mice by destabilisation of the medial meniscus. Analysis of OA progression revealed that the intensity and duration of chondrocyte loss and cartilage lesion formation were significantly different in MCL-MM vs DMM. Firstly, apoptosis was seen prior to week two and was narrowly restricted to the weight bearing area. Four weeks post injury the magnitude of apoptosis led to a 40–60% reduction of chondrocytes in the non-calcified zone. Secondly, the progression of cell loss preceded the structural changes of the cartilage spatio-temporally. Lastly, while proteoglycan loss was similar in both models, collagen type II degradation only occurred more prominently in MCL-MM. Dynamics of chondrocyte loss and lesion formation in preclinical models has important implications for validating new therapeutic strategies. Our work could be helpful in assessing the feasibility and expected response of the DMM- and the MCL-MM models to chondrocyte mediated therapies

Оборудование для испытания листовых конструкционных материалов при двухосном растяжении. Сообщение 1. Испытания односторонним давлением рабочей среды

Рассмотрены конструктивные особенности оборудования для исследования прочности и закономерностей разрушения листовых конструкционных материалов при двухосном растяжении путем нагружения образцов односторонним давлением рабочей среды. Предложены решения ряда проблем методического характера, связанных с испытаниями при высоких уровнях давления рабочей среды, что позволяет обеспечить необходимые режимы охлаждения образцов, снизить уровень энергии разрушения, повысить надежность и безопасность испытаний.Розглянуто конструктивні особливості устаткування для дослідження міцності і закономірностей руйнування листових конструкційних матеріалів при двовісному розтязі зразків одностороннім тиском робочого середовища. Запропоновано рішення ряду проблем методичного характеру, що пов’язані з випробуваннями при високих рівнях тиску робочого середовища. Це дозволить забезпечити необхідні режими охолодження зразків, знизити рівень енергії руйнування, підвищити надійность та безпеку випробувань.Design features of the equipment for studying strength and regularities of fracture of sheet structural materials in biaxial tension by subjecting specimens to one-sided pressure of a working medium are considered. Solutions were suggested for a number of methodological problems related to testing at high levels of pressure of a working medium. These solutions make it possible to provide necessary conditions of cooling of specimens, lower the level of fracture energy, and improve reliability and safety of the tests

Epigenetic Mechanisms of ART-Related Imprinting Disorders: Lessons From iPSC and Mouse Models.

The rising frequency of ART-conceived births is accompanied by the need for an improved understanding of the implications of ART on gametes and embryos. Increasing evidence from mouse models and human epidemiological data suggests that ART procedures may play a role in the pathophysiology of certain imprinting disorders (IDs), including Beckwith-Wiedemann syndrome, Silver-Russell syndrome, Prader-Willi syndrome, and Angelman syndrome. The underlying molecular basis of this association, however, requires further elucidation. In this review, we discuss the epigenetic and imprinting alterations of in vivo mouse models and human iPSC models of ART. Mouse models have demonstrated aberrant regulation of imprinted genes involved with ART-related IDs. In the past decade, iPSC technology has provided a platform for patient-specific cellular models of culture-associated perturbed imprinting. However, despite ongoing efforts, a deeper understanding of the susceptibility of iPSCs to epigenetic perturbation is required if they are to be reliably used for modelling ART-associated IDs. Comparing the patterns of susceptibility of imprinted genes in mouse models and IPSCs in culture improves the current understanding of the underlying mechanisms of ART-linked IDs with implications for our understanding of the influence of environmental factors such as culture and hormone treatments on epigenetically important regions of the genome such as imprints

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