Leadership Education in Neurodevelopmental and Related Disabilities (LEND) programs are interdisciplinary, graduate-level training programs that seek to promote improved outcomes for individuals with ...disabilities and their families. Many of these programs include individuals with disabilities as members of the self-advocacy discipline. In this study, 10 self-advocate trainees were interviewed to provide insight into the value of including self-advocates in training and the kinds of accommodations and supports that facilitated their success and inclusion. Interviewees endorsed the importance of including self-advocates in LEND programs. Although several accommodations were discussed as helpful, interpersonal supports from faculty and peers were equally important in ensuring their success and inclusion in LEND. The findings from this study provide support for the expansion of self-advocacy as a formal discipline in LEND programs.
Successful family-professional partnerships (FPP) have been shown to positively impact both satisfaction with care and health outcomes for children with disabilities and their families. Many ...healthcare training programs have recognized the benefit of FPP training and often include learning experiences that feature families as teachers or mentors. However, most research on FPP training has focused on professionals' experiences, and not on families' experience in the roles of mentors and experts. The Leadership Education in Neurodevelopmental and Related Disabilities (LEND) program is a graduate-level interdisciplinary training program with sites across the country. LEND programs train future healthcare and service professionals in the disability field and often utilize a Family Mentor Experience (FME) as one aspect of their training. This study used qualitative interviews to examine the experiences of eight family mentors who worked with trainees in one LEND program. Overall, the family mentors expressed positive views regarding the FME, describing how it allowed them to connect with trainees, other families, and community resources, as well as educating trainees. Family mentors also identified several facilitators and barriers to participation. Study findings provide information on the FFP's impact on family mentors and guidance on how programs can support sustainable, effective FPP experiences.
Clostridioides difficile (C. diff.) infection (CDI) is a leading cause of hospital acquired diarrhea in North America and Europe and a major cause of morbidity and mortality. Known risk factors do ...not fully explain CDI susceptibility, and genetic susceptibility is suggested by the fact that some patients with colons that are colonized with C. diff. do not develop any infection while others develop severe or recurrent infections. To identify common genetic variants associated with CDI, we performed a genome-wide association analysis in 19,861 participants (1349 cases; 18,512 controls) from the Electronic Medical Records and Genomics (eMERGE) Network. Using logistic regression, we found strong evidence for genetic variation in the DRB locus of the MHC (HLA) II region that predisposes individuals to CDI (P > 1.0 × 10
; OR 1.56). Altered transcriptional regulation in the HLA region may play a role in conferring susceptibility to this opportunistic enteric pathogen.
Genome-wide association studies (GWAS) are being conducted at an unprecedented rate in population-based cohorts and have increased our understanding of the pathophysiology of complex disease. ...Regardless of context, the practical utility of this information will ultimately depend upon the quality of the original data. Quality control (QC) procedures for GWAS are computationally intensive, operationally challenging, and constantly evolving. Here we enumerate some of the challenges in QC of GWAS data and describe the approaches that the electronic MEdical Records and Genomics (eMERGE) network is using for quality assurance in GWAS data, thereby minimizing potential bias and error in GWAS results. We discuss common issues associated with QC of GWAS data, including data file formats, software packages for data manipulation and analysis, sex chromosome anomalies, sample identity, sample relatedness, population substructure, batch effects, and marker quality. We propose best practices and discuss areas of ongoing and future research.
Combination treatment with pegylated‐interferon‐alpha (PEG IFN‐α) and ribavirin, the current recommended therapy for chronic hepatitis C virus (HCV) infection, results in a sustained virological ...response (SVR) in only about half of patients. Because genes involved in the interferon‐alpha pathway may affect antiviral responses, we analyzed the relationship between variants in these genes and SVR among participants in the Hepatitis C Antiviral Long‐Term treatment Against Cirrhosis (HALT‐C) trial. Patients had advanced chronic hepatitis C that had previously failed to respond to interferon‐based treatment. Participants were treated with peginterferon‐α2a and ribavirin during the trial. Subjects with undetectable HCV RNA at week 72 were considered to have had an SVR. Subjects with detectable HCV RNA at week 20 were considered nonresponders. We used TaqMan assays to genotype 56 polymorphisms found in 13 genes in the interferon‐alpha pathway. This analysis compares genotypes for participants with an SVR to nonresponders. The primary analysis was restricted to European American participants because a priori statistical power was low among the small number (n = 131) of African American patients. We used logistic regression to control the effect of other variables that are associated with treatment response. Among 581 European American patients, SVR was associated with IFNAR1 IVS1‐22G (adjusted odds ratio, 0.57; P = 0.02); IFNAR2 Ex2‐33C (adjusted odds ratio, 2.09; P = 0.02); JAK1 IVS22+112T (adjusted odds ratio, 1.66; P = 0.04); and ADAR Ex9+14A (adjusted odds ratio, 1.67; P = 0.03). For the TYK2‐2256A promoter region variant, a borderline association was present among European American participants (OR, 1.51; P = 0.05) and a strong relationship among African American patients; all 10 with SVR who were genotyped for TYK2 ‐2256 carried the A variant compared with 68 of 120 (57%) nonresponders (P = 0.006). Conclusion: Genetic polymorphisms in the interferon‐α pathway may affect responses to antiviral therapy of chronic hepatitis C. (HEPATOLOGY 2009.)
There have been few genome-wide association studies (GWAS) of prostate cancer among diverse populations. To search for novel prostate cancer risk variants, we conducted GWAS of prostate cancer in ...Japanese and Latinos. In addition, we tested prostate cancer risk variants and developed genetic risk models of prostate cancer for Japanese and Latinos.
Our first-stage GWAS of prostate cancer included Japanese (cases/controls = 1,033/1,042) and Latino (cases/controls = 1,043/1,057) from the Multiethnic Cohort (MEC). Significant associations from stage I (P < 1.0 × 10(-4)) were examined in silico in GWAS of prostate cancer (stage II) in Japanese (cases/controls = 1,583/3,386) and Europeans (cases/controls = 1,854/1,894).
No novel stage I single-nucleotide polymorphism (SNP) outside of known risk regions reached genome-wide significance. For Japanese, in stage I, the most notable putative novel association was seen with 10 SNPs (P ≤ 8.0 × 10(-6)) at chromosome 2q33; however, this was not replicated in stage II. For Latinos, the most significant association was observed with rs17023900 at the known 3p12 risk locus (stage I: OR = 1.45; P = 7.01 × 10(-5) and stage II: OR = 1.58; P = 3.05 × 10(-7)). The majority of the established risk variants for prostate cancer, 79% and 88%, were positively associated with prostate cancer in Japanese and Latinos (stage I), respectively. The cumulative effects of these variants significantly influence prostate cancer risk (OR per allele = 1.10; P = 2.71 × 10(-25) and OR = 1.07; P = 1.02 × 10(-16) for Japanese and Latinos, respectively).
Our GWAS of prostate cancer did not identify novel genome-wide significant variants. However, our findings show that established risk variants for prostate cancer significantly contribute to risk among Japanese and Latinos.
Combination treatment with pegylated-interferon-α and ribavirin, the current recommended therapy for chronic hepatitis C virus (HCV) infection, results in a sustained virological response (SVR) in ...only about half of patients. Because genes involved in the interferon-α pathway may affect anti-viral responses, we analyzed the relationship between variants in these genes and SVR among participants in the HALT-C trial. Patients had advanced chronic hepatitis C and had previously failed to respond to interferon-based treatment. Participants were treated with peginterferon-α2a and ribavirin during the trial. Subjects with undetectable HCV RNA at week 72 were considered to have had an SVR. Subjects with detectable HCV RNA at week 20 were considered non-responders. We used TaqMan assays to genotype 56 polymorphisms found in 13 genes in the interferon-α pathway. This analysis compares genotypes for participants with an SVR to non-responders. The primary analysis was restricted to European American participants because
a priori
statistical power was low among the small number (n=131) of African American patients. We used logistic regression to control the effect of other variables that are associated with treatment response. Among 581 European American patients, SVR was associated with
IFNAR1
IVS1-22G (adjusted odds ratio aOR, 0.57; p=0.02);
IFNAR2
Ex2-33C (aOR, 2.09; p=0.02);
JAK1
IVS22+112T (aOR, 1.66; p=0.04); and
ADAR
Ex9+14A (aOR, 1.67; p=0.03). For the
TYK2
-2256A promoter region variant a borderline association was present among European American participants (OR, 1.51; p=0.05) and a strong relationship among African American patients; all 10 with SVR who were genotyped for
TYK2
-2256 carried the A variant compared to 68/120 (57%) non-responders (p=0.006). In conclusion, genetic polymorphisms in the interferon-α pathway may affect responses to antiviral therapy of chronic hepatitis C.
Abstract
A growing interest in aptamer research, as evidenced by the increase in aptamer publications over the years, has led to calls for a go-to site for aptamer information. A comprehensive, ...publicly available aptamer dataset, which may be a repository for aptamer data, standardize aptamer reporting, and generate opportunities to expand current research in the field, could meet such a demand. There have been several attempts to create aptamer databases; however, most have been abandoned or removed entirely from public view. Inspired by previous efforts, we have published the UTexas Aptamer Database, https://sites.utexas.edu/aptamerdatabase, which includes a publicly available aptamer dataset and a searchable database containing a subset of all aptamer data collected to date (1990–2022). The dataset contains aptamer sequences, binding and selection information. The information is regularly reviewed internally to ensure accuracy and consistency across all entries. To support the continued curation and review of aptamer sequence information, we have implemented sustaining mechanisms, including researcher training protocols, an aptamer submission form, data stored separately from the database platform, and a growing team of researchers committed to updating the database. Currently, the UTexas Aptamer Database is the largest in terms of the number of aptamer sequences with 1,443 internally reviewed aptamer records.
Graphical Abstract
Graphical Abstract
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