Adapting Participatory Action Research to Include Individuals with Intellectual and Developmental Disabilities during the COVID-19 Global Pandemic

Participatory action research (PAR), or the inclusion of those affected by the issues being studied, is a growing area of emphasis in disability research. The principles of PAR align with those of the disability rights movement, such that full inclusion and “nothing about us without us” extends as much to research as it does to any other area of life. Moreover, PAR allows for meaningful input from people with intellectual and developmental disabilities (I/DD), which enhances the likelihood that research results are relevant and important to the disability community. As research activity resumes and is adapted to the context of a global pandemic, it is crucial that a balance is struck to optimize the safety of individuals with I/DD without taking steps backwards from the progress towards more meaningful inclusion in research. Lessons learned from past participatory research projects have demonstrated that accommodations to enable equitable participation of individuals with IDD in the research process are crucial. COVID-19 has significantly affected the lives of individuals with I/DD directly; however, COVID-19 has also affected those with I/DD indirectly through the disruption to critical intervention and other clinical research. As research processes are adapted to align with COVID-19 guidelines, the inclusion of individuals with I/DD via PAR needs to be adapted as well. Recommendations for the continuation of PAR in the context of COVID-19 will be discussed as well as ways in which accommodations can be modified to this new context

Self-Esteem in Second Life: An inWorld Group Intervention for Women with Disabilities

We are developing and investigating the feasibility of a self-esteem enhancement intervention in Second Life for women with physical disabilities. We adapted the curriculum of a previously tested workshop intervention to include features unique to this environment. Results of the beta test were very positive. Everyone involved showed considerable enthusiasm for exploring the new world of SL. The group leaders were challenged to resolve technical problems on every occasion, but these diminished and were perceived as manageable as the intervention progressed. Beta testers gave positive ratings to the information presented, organization, and usefulness of the intervention and found it very enjoyable although fatigue and stress limited the participation of some. They appreciated the use of Internet technology as an accommodation to their disability, in place of requiring transportation and additional energy expenditure to attend face-to-face meetings. Research issues related to engagement, measurement, and participant safety, as well as future research directions, are discussed. We conclude that SL has great potential for delivering health promotion interventions to women with physical disabilities

Abuse Assessment Screen–Disability (AAS-D): Measuring Frequency, Type, and Perpetrator of Abuse toward Women with Physical Disabilities

An interview questionnaire was presented to a multiethnic sample of 511 women, age 18–64 years, at public and private specialty clinics to determine the frequency, type, and perpetrator of abuse toward women with physical disabilities. The four-question Abuse Assessment Screen–Disability (AAS-D) instrument detected a 9.8% prevalence (50 of 511) of abuse during the previous 12 months. Using two standard physical and sexual assault questions, 7.8% of the women (40 of 511) reported abuse. The two disability-related questions detected an additional 2.0% of the women (10 of 511) as abused. Women defining themselves as other than black, white, or Hispanic (i.e., Asian, mixed ethnic background) were more likely to report physical or sexual abuse or both, whereas disability-related abuse was reported almost exclusively by white women. The perpetrator of physical or sexual abuse was most likely to be an intimate partner. Disability-related abuse was attributed equally to an intimate partner, a care provider, or a health professional. This study concludes that both traditional abuse-focused questions and disability-specific questions are required to detect abuse toward women with physical disabilities

Using the Theoretical Domains Framework (TDF) to understand adherence to multiple evidence-based indicators in primary care : a qualitative study

BACKGROUND: There are recognised gaps between evidence and practice in general practice, a setting posing particular implementation challenges. We earlier screened clinical guideline recommendations to derive a set of 'high-impact' indicators based upon criteria including potential for significant patient benefit, scope for improved practice and amenability to measurement using routinely collected data. Here, we explore health professionals' perceived determinants of adherence to these indicators, examining the degree to which determinants were indicator-specific or potentially generalisable across indicators. METHODS: We interviewed 60 general practitioners, practice nurses and practice managers in West Yorkshire, the UK, about adherence to four indicators: avoidance of risky prescribing; treatment targets in type 2 diabetes; blood pressure targets in treated hypertension; and anticoagulation in atrial fibrillation. Interview questions drew upon the Theoretical Domains Framework (TDF). Data were analysed using framework analysis. RESULTS: Professional role and identity and environmental context and resources featured prominently across all indicators whilst the importance of other domains, for example, beliefs about consequences, social influences and knowledge varied across indicators. We identified five meta-themes representing more general organisational and contextual factors common to all indicators. CONCLUSIONS: The TDF helped elicit a wide range of reported determinants of adherence to 'high-impact' indicators in primary care. It was more difficult to pinpoint which determinants, if targeted by an implementation strategy, would maximise change. The meta-themes broadly underline the need to align the design of interventions targeting general practices with higher level supports and broader contextual considerations. However, our findings suggest that it is feasible to develop interventions to promote the uptake of different evidence-based indicators which share common features whilst also including content-specific adaptations

Intrinsic genetic characteristics determine tumor-modifying capacity of fibroblasts: matrix metalloproteinase-3 5A/5A genotype enhances breast cancer cell invasion

Background Stromal fibroblasts can contribute to tumor invasion through the release of matrix metalloproteinases (MMPs). Population studies have suggested that single nucleotide polymorphisms (SNPs) in MMP genes influence levels of expression and may be associated with breast cancer risk and with disease progression. This study directly examined the impact of MMP SNP genotype on the ability of host fibroblasts to promote tumor cell invasion. Methods Primary breast fibroblasts were isolated from patients with (n = 13) or without (n = 19) breast cancer, and their ability to promote breast cancer cell invasion was measured in in vitro invasion assays. Fibroblast invasion-promoting capacity (IPC) was analyzed in relation to donor type (tumor or non-tumor patient), MMP-1, MMP-3, and MMP-9 SNP genotype and MMP activity using independent samples t test and analysis of variance. All statistical tests were two-sided. Results Tumor-derived fibroblasts promoted higher levels of invasion than normal fibroblasts (p = 0.041). When IPC was related to genotype, higher levels of IPC were generated by tumor fibroblasts with the high-expressing MMP-3 5A/5A genotype compared with the 5A/6A and 6A/6A genotypes (p = 0.05 and 0.07, respectively), and this was associated with enhanced MMP-3 release. The functional importance of MMP-3 was demonstrated by enhanced invasion in the presence of recombinant MMP-3, whereas reduction occurred in the presence of a specific MMP-3 inhibitor. An inverse relationship was demonstrated between fibroblast IPC and the high-expressing MMP-1 genotype (p = 0.031), but no relationship was seen with MMP-9 SNP status. In contrast, normal fibroblasts showed no variation in IPC in relation to MMP genotype, with MMP-3 5A/5A fibroblasts exhibiting significantly lower levels of IPC than their tumor-derived counterparts (p = 0.04). Conclusion This study has shown that tumor-derived fibroblasts exhibit higher levels of IPC than normal fibroblasts and that the MMP-3 5A/5A genotype contributes to this through enhanced MMP-3 release. Despite a high-expressing genotype, normal fibroblasts do not exhibit higher IPC or enhanced MMP release. This suggests that more complex changes occur in tumor-derived fibroblasts, enabling full expression of the MMP SNP genotype and these possibly are epigenetic in nature. The results do suggest that, in women with breast cancer, a high-expressing MMP-3 genotype may promote tumor progression more effectively

LTR Retrotransposons in Fungi

Transposable elements with long terminal direct repeats (LTR TEs) are one of the best studied groups of mobile elements. They are ubiquitous elements present in almost all eukaryotic genomes. Their number and state of conservation can be a highlight of genome dynamics. We searched all published fungal genomes for LTR-containing retrotransposons, including both complete, functional elements and remnant copies. We identified a total of over 66,000 elements, all of which belong to the Ty1/Copia or Ty3/Gypsy superfamilies. Most of the detected Gypsy elements represent Chromoviridae, i.e. they carry a chromodomain in the pol ORF. We analyzed our data from a genome-ecology perspective, looking at the abundance of various types of LTR TEs in individual genomes and at the highest-copy element from each genome. The TE content is very variable among the analyzed genomes. Some genomes are very scarce in LTR TEs (<50 elements), others demonstrate huge expansions (>8000 elements). The data shows that transposon expansions in fungi usually involve an increase both in the copy number of individual elements and in the number of element types. The majority of the highest-copy TEs from all genomes are Ty3/Gypsy transposons. Phylogenetic analysis of these elements suggests that TE expansions have appeared independently of each other, in distant genomes and at different taxonomical levels. We also analyzed the evolutionary relationships between protein domains encoded by the transposon pol ORF and we found that the protease is the fastest evolving domain whereas reverse transcriptase and RNase H evolve much slower and in correlation with each other

Systems Biology of the Clock in Neurospora crassa

A model-driven discovery process, Computing Life, is used to identify an ensemble of genetic networks that describe the biological clock. A clock mechanism involving the genes white-collar-1 and white-collar-2 (wc-1 and wc-2) that encode a transcriptional activator (as well as a blue-light receptor) and an oscillator frequency (frq) that encodes a cyclin that deactivates the activator is used to guide this discovery process through three cycles of microarray experiments. Central to this discovery process is a new methodology for the rational design of a Maximally Informative Next Experiment (MINE), based on the genetic network ensemble. In each experimentation cycle, the MINE approach is used to select the most informative new experiment in order to mine for clock-controlled genes, the outputs of the clock. As much as 25% of the N. crassa transcriptome appears to be under clock-control. Clock outputs include genes with products in DNA metabolism, ribosome biogenesis in RNA metabolism, cell cycle, protein metabolism, transport, carbon metabolism, isoprenoid (including carotenoid) biosynthesis, development, and varied signaling processes. Genes under the transcription factor complex WCC ( = WC-1/WC-2) control were resolved into four classes, circadian only (612 genes), light-responsive only (396), both circadian and light-responsive (328), and neither circadian nor light-responsive (987). In each of three cycles of microarray experiments data support that wc-1 and wc-2 are auto-regulated by WCC. Among 11,000 N. crassa genes a total of 295 genes, including a large fraction of phosphatases/kinases, appear to be under the immediate control of the FRQ oscillator as validated by 4 independent microarray experiments. Ribosomal RNA processing and assembly rather than its transcription appears to be under clock control, suggesting a new mechanism for the post-transcriptional control of clock-controlled genes

A meta-analysis of previous falls and subsequent fracture risk in cohort studies

NC Harvey acknowledges funding from the UK Medical Research Council (MC_PC_21003; MC_PC_21001). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005. Funding for the MrOS USA study comes from the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. Funding for the SOF study comes from the National Institute on Aging (NIA), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), supported by grants (AG05407, AR35582, AG05394, AR35584, and AR35583). Funding for the Health ABC study was from the Intramural research program at the National Institute on Aging under the following contract numbers: NO1-AG-6–2101, NO1-AG-6–2103, and NO1-AG-6–2106.Peer reviewedPostprin