It is well established that the incidence, prevalence and presentation of mental disorders differ by gender, ethnicity and age, and there is evidence that there is also differential representation in ...mental health research by these characteristics. The aim of this paper is to a) review the current literature on the nature of barriers to participation in mental health research, with particular reference to gender, age and ethnicity; b) review the evidence on the effectiveness of strategies used to overcome these barriers.
Studies published up to December 2008 were identified using MEDLINE, PsycINFO and EMBASE using relevant mesh headings and keywords.
Forty-nine papers were identified. There was evidence of a wide range of barriers including transportation difficulties, distrust and suspicion of researchers, and the stigma attached to mental illness. Strategies to overcome these barriers included the use of bilingual staff, assistance with travel, avoiding the use of stigmatising language in marketing material and a focus on education about the disorder under investigation. There were very few evaluations of such strategies, but there was evidence that ethnically matching recruiters to potential participants did not improve recruitment rates. Educational strategies were helpful and increased recruitment.
Mental health researchers should consider including caregivers in recruitment procedures where possible, provide clear descriptions of study aims and describe the representativeness of their sample when reporting study results. Studies that systematically investigate strategies to overcome barriers to recruitment are needed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Studies of psychiatric populations have reported associations between childhood adversity and volumes of stress-related brain structures. This meta-analysis investigated these associations in ...non-clinical samples and therefore independent of the effects of severe mental health difficulties and their treatment.
The MEDLINE database was searched for magnetic resonance imaging studies measuring brain structure in adults with and without childhood adversity. Fifteen eligible papers (1781 participants) reporting hippocampal volumes and/or amygdala volumes were pooled using a random effects meta-analysis.
Those with childhood adversity had lower hippocampus volumes (hedges g = - 0.15,
= 0.010). Controlling for gender, this difference became less evident (hedges g = - 0.12,
= 0.124). This association differed depending on whether studies included participants with some psychopathology, though this may be due to differences in the type of adversity these studies examined. There was no strong evidence of any differences in amygdala volume.
Childhood adversity may have only a modest impact on stress-related brain structures in those without significant mental health difficulties.
To understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19, we developed a mechanistic, within-host mathematical model and ...virtual patient cohort. Our results suggest that virtual patients with low production rates of infected cell derived IFN subsequently experienced highly inflammatory disease phenotypes, compared to those with early and robust IFN responses. In these in silico patients, the maximum concentration of IL-6 was also a major predictor of CD8+ T cell depletion. Our analyses predicted that individuals with severe COVID-19 also have accelerated monocyte-to-macrophage differentiation mediated by increased IL-6 and reduced type I IFN signalling. Together, these findings suggest biomarkers driving the development of severe COVID-19 and support early interventions aimed at reducing inflammation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Prologue: Several years ago, when we began to question microinstability as the universal cause of the disabled throwing shoulder, we knew that we were questioning a sacrosanct tenet of American ...sports medicine. However, we were comfortable in our skepticism because we were relying on arthroscopic insights, clinical observations, and biomechanical data, thereby challenging unverified opinion with science. In so doing, we assembled a unified concept of the disabled throwing shoulder that encompassed biomechanics, pathoanatomy, kinetic chain considerations, surgical treatment, and rehabilitation. In developing this unified concept, we rejected much of the conventional wisdom of microinstability-based treatment in favor of more successful techniques (as judged by comparative outcomes) that were based on sound biomechanical concepts that had been scientifically verified. Although we have reported various components of this unified concept previously, we have been urged by many of our colleagues to publish this information together in a single reference for easy access by orthopaedic surgeons who treat overhead athletes. We are grateful to the editors of Arthroscopy for allowing us to present our view of the disabled throwing shoulder. Part I: Pathoanatomy and Biomechanics is presented in this issue. Part II: Evaluation and Treatment of SLAP Lesions in Throwers will be presented in the May-June issue. Part III: The “SICK” Scapula, Scapular Dyskinesis, the Kinetic Chain, and Rehabilitation will be presented in the July-August issue. We hope you find it thought-provoking and compelling.
Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 19, No 4 (April), 2003: pp 404–420
Social exclusion and mental health Morgan, Craig; Burns, Tom; Fitzpatrick, Ray ...
British journal of psychiatry,
12/2007, Letnik:
191, Številka:
6
Journal Article
On July 19th, 2023, the National Institute of Allergy and Infectious Diseases co-organized a workshop with the Society of Mathematical Biology, with the authors of this paper as the organizing ...committee. The workshop, “Bridging multiscale modeling and practical clinical applications in infectious diseases” sought to create an environment for mathematical modelers, statisticians, and infectious disease researchers and clinicians to exchange ideas and perspectives.
Glioblastoma is a complex disease that is difficult to treat. Network and data science offer alternative approaches to classical bioinformatics pipelines to study gene expression patterns from ...single-cell datasets, helping to distinguish genes associated with the control of differentiation and aggression. To identify the key molecular regulators of the networks driving glioblastoma/GSC and predict their cell fate dynamics, we applied a host of data theoretic techniques to gene expression patterns from pediatric and adult glioblastoma, and adult glioma-derived stem cells (GSCs). We identified eight transcription factors (OLIG1/2, TAZ, GATA2, FOXG1, SOX6, SATB2, and YY1) and four signaling genes (ATL3, MTSS1, EMP1, and TPT1) as coordinators of cell state transitions and, thus, clinically targetable putative factors differentiating pediatric and adult glioblastomas from adult GSCs. Our study provides strong evidence of complex systems approaches for inferring complex dynamics from reverse-engineering gene networks, bolstering the search for new clinically relevant targets in glioblastoma.
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•Complex cell fate attractors capture glioblastoma differentiation dynamics•Graph theoretic approaches decode master regulators of GBM glioblastoma cell fate decisions•Network dynamics of pediatric glioblastoma resemble adult GSCs•Transcriptional networks may help reprogram glioblastoma behavioral patterns
Gene network; Bioinformatics; Cancer
Granulosa cell tumors (GCT) constitute only ~5% of ovarian neoplasms yet have significant consequences, as up to 80% of women with recurrent GCT will die of the disease. This study investigated the ...effectiveness of procaspase-activating compound 1 (PAC-1), an activator of procaspase-3, in treating adult GCT (AGCT) in combination with selected apoptosis-inducing agents. Sensitivity of the AGCT cell line KGN to these drugs, alone or in combination with PAC-1, was tested using a viability assay. Our results show a wide range in cytotoxic activity among the agents tested. Synergy with PAC-1 was most pronounced, both empirically and by mathematical modelling, when combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). This combination showed rapid kinetics of apoptosis induction as determined by caspase-3 activity, and strongly synergistic killing of both KGN as well as patient samples of primary and recurrent AGCT. We have demonstrated that the novel combination of two pro-apoptotic agents, TRAIL and PAC-1, significantly amplified the induction of apoptosis in AGCT cells, warranting further investigation of this combination as a potential therapy for AGCT.
BackgroundImmunotherapies, driven by immune-mediated antitumorigenicity, offer the potential for significant improvements to the treatment of multiple cancer types. Identifying therapeutic strategies ...that bolster antitumor immunity while limiting immune suppression is critical to selecting treatment combinations and schedules that offer durable therapeutic benefits. Combination oncolytic virus (OV) therapy, wherein complementary OVs are administered in succession, offer such promise, yet their translation from preclinical studies to clinical implementation is a major challenge. Overcoming this obstacle requires answering fundamental questions about how to effectively design and tailor schedules to provide the most benefit to patients.MethodsWe developed a computational biology model of combined oncolytic vaccinia (an enhancer virus) and vesicular stomatitis virus (VSV) calibrated to and validated against multiple data sources. We then optimized protocols in a cohort of heterogeneous virtual individuals by leveraging this model and our previously established in silico clinical trial platform.ResultsEnhancer multiplicity was shown to have little to no impact on the average response to therapy. However, the duration of the VSV injection lag was found to be determinant for survival outcomes. Importantly, through treatment individualization, we found that optimal combination schedules are closely linked to tumor aggressivity. We predicted that patients with aggressively growing tumors required a single enhancer followed by a VSV injection 1 day later, whereas a small subset of patients with the slowest growing tumors needed multiple enhancers followed by a longer VSV delay of 15 days, suggesting that intrinsic tumor growth rates could inform the segregation of patients into clinical trials and ultimately determine patient survival. These results were validated in entirely new cohorts of virtual individuals with aggressive or non-aggressive subtypes.ConclusionsBased on our results, improved therapeutic schedules for combinations with enhancer OVs can be studied and implemented. Our results further underline the impact of interdisciplinary approaches to preclinical planning and the importance of computational approaches to drug discovery and development.
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