Tracking Assaultâ injured, Drugâ using Youth in Longitudinal Research: Followâ up Methods

ObjectivesViolence is one of the leading causes of death among youth ages 14 to 24. Hospitalâ and emergency department (ED)â based violence prevention programs are increasingly becoming a critical part of public health efforts; however, evaluation of prevention efforts is needed to create evidenceâ based best practices. Retention of study participants is key to evaluations, although little literature exists regarding optimizing followâ up methods for violently injured youth. This study aims to describe the methods for retention in youth violence studies and the characteristics of hardâ toâ reach participants.MethodsThe Flint Youth Injury (FYI) Study is a prospective study following a cohort of assaultâ injured, drugâ using youth recruited in an urban ED, and a comparison population of drugâ using youth seeking medical or nonâ violenceâ related injury care. Validated survey instruments were administered at baseline and four followâ up time points (6, 12, 18, and 24 months). Followâ up contacts used a variety of strategies and all attempts were coded by type and level of success. Regression analysis was used to predict contact difficulty and followâ up interview completion at 24 months.ResultsA total of 599 patients (ages 14â 24) were recruited from the ED (mean ± SD age = 20.1 ± 2.4 years, 41.2% female, 58.2% African American), with followâ up rates at 6, 12, 18, and 24 months of 85.3%, 83.7% 84.2%, and 85.3%, respectively. Participant contact efforts ranged from two to 53 times per followâ up time frame to complete a followâ up appointment, and more than 20% of appointments were completed off site at community locations (e.g., participantsâ homes, jail/prison). Participants who were younger (p < 0.05) and female (p < 0.01) were more likely to complete their 24â month followâ up interview. Participants who sought care in the ED for assault injury (p < 0.05) and had a substance use disorder (p < 0.01) at baseline required fewer contact attempts to complete their 24â month followâ up, while participants reporting a fight within the immediate 3 months before their 24â month followâ up (p < 0.01) required more intensive contact efforts.ConclusionsThe FYI study demonstrated that achieving high followâ up rates for a difficultâ toâ track, violentlyâ injured ED population is feasible through the use of established contact strategies and a variety of interview locations. Results have implications for followâ up strategies planned as part of other violence prevention studies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146571/1/acem13495_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146571/2/acem13495.pd

Potential opportunities and challenges of deploying next generation sequencing and CRISPR-cas systems to support diagnostics and surveillance towards malaria control and elimination in Africa

Recent developments in molecular biology and genomics have revolutionized biology and medicine mainly in the developed world. The application of next generation sequencing (NGS) and CRISPR-Cas tools is now poised to support endemic countries in the detection, monitoring and control of endemic diseases and future epidemics, as well as with emerging and re-emerging pathogens. Most low and middle income countries (LMICs) with the highest burden of infectious diseases still largely lack the capacity to generate and perform bioinformatic analysis of genomic data. These countries have also not deployed tools based on CRISPR-Cas technologies. For LMICs including Tanzania, it is critical to focus not only on the process of generation and analysis of data generated using such tools, but also on the utilization of the findings for policy and decision making. Here we discuss the promise and challenges of NGS and CRISPR-Cas in the context of malaria as Africa moves towards malaria elimination. These innovative tools are urgently needed to strengthen the current diagnostic and surveillance systems. We discuss ongoing efforts to deploy these tools for malaria detection and molecular surveillance highlighting potential opportunities presented by these innovative technologies as well as challenges in adopting them. Their deployment will also offer an opportunity to broadly build in-country capacity in pathogen genomics and bioinformatics, and to effectively engage with multiple stakeholders as well as policy makers, overcoming current workforce and infrastructure challenges. Overall, these ongoing initiatives will build the malaria molecular surveillance capacity of African researchers and their institutions, and allow them to generate genomics data and perform bioinformatics analysis in-country in order to provide critical information that will be used for real-time policy and decision-making to support malaria elimination on the continent

Hospital characteristics associated with highly automated and usable clinical information systems in Texas, United States

<p>Abstract</p> <p>Background</p> <p>A hospital's clinical information system may require a specific environment in which to flourish. This environment is not yet well defined. We examined whether specific hospital characteristics are associated with highly automated and usable clinical information systems.</p> <p>Methods</p> <p>This was a cross-sectional survey of 125 urban hospitals in Texas, United States using the Clinical Information Technology Assessment Tool (CITAT), which measures a hospital's level of automation based on physician interactions with the information system. Physician responses were used to calculate a series of CITAT scores: automation and usability scores, four automation sub-domain scores, and an overall clinical information technology (CIT) score. A multivariable regression analysis was used to examine the relation between hospital characteristics and CITAT scores.</p> <p>Results</p> <p>We received a sufficient number of physician responses at 69 hospitals (55% response rate). Teaching hospitals, hospitals with higher IT operating expenses (>$1 million annually), IT capital expenses (>$75,000 annually) and hospitals with larger IT staff (≥ 10 full-time staff) had higher automation scores than hospitals that did not meet these criteria (p < 0.05 in all cases). These findings held after adjustment for bed size, total margin, and ownership (p < 0.05 in all cases). There were few significant associations between the hospital characteristics tested in this study and usability scores.</p> <p>Conclusion</p> <p>Academic affiliation and larger IT operating, capital, and staff budgets are associated with more highly automated clinical information systems.</p

Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states

<p>Abstract</p> <p>Background</p> <p>Colon cancer arises from the accumulation of multiple genetic and epigenetic alterations to normal colonic tissue. microRNAs (miRNAs) are small, non-coding regulatory RNAs that post-transcriptionally regulate gene expression. Differential miRNA expression in cancer versus normal tissue is a common event and may be pivotal for tumor onset and progression.</p> <p>Methods</p> <p>To identify miRNAs that are differentially expressed in tumors and tumor subtypes, we carried out highly sensitive expression profiling of 735 miRNAs on samples obtained from a statistically powerful set of tumors (n = 80) and normal colon tissue (n = 28) and validated a subset of this data by qRT-PCR.</p> <p>Results</p> <p>Tumor specimens showed highly significant and large fold change differential expression of the levels of 39 miRNAs including miR-135b, miR-96, miR-182, miR-183, miR-1, and miR-133a, relative to normal colon tissue. Significant differences were also seen in 6 miRNAs including miR-31 and miR-592, in the direct comparison of tumors that were deficient or proficient for mismatch repair. Examination of the genomic regions containing differentially expressed miRNAs revealed that they were also differentially methylated in colon cancer at a far greater rate than would be expected by chance. A network of interactions between these miRNAs and genes associated with colon cancer provided evidence for the role of these miRNAs as oncogenes by attenuation of tumor suppressor genes.</p> <p>Conclusion</p> <p>Colon tumors show differential expression of miRNAs depending on mismatch repair status. miRNA expression in colon tumors has an epigenetic component and altered expression that may reflect a reversion to regulatory programs characteristic of undifferentiated proliferative developmental states.</p

miRNA Expression in Colon Polyps Provides Evidence for a Multihit Model of Colon Cancer

Changes in miRNA expression are a common feature in colon cancer. Those changes occurring in the transition from normal to adenoma and from adenoma to carcinoma, however, have not been well defined. Additionally, miRNA changes among tumor subgroups of colon cancer have also not been adequately evaluated. In this study, we examined the global miRNA expression in 315 samples that included 52 normal colonic mucosa, 41 tubulovillous adenomas, 158 adenocarcinomas with proficient DNA mismatch repair (pMMR) selected for stage and age of onset, and 64 adenocarcinomas with defective DNA mismatch repair (dMMR) selected for sporadic (n = 53) and inherited colon cancer (n = 11). Sporadic dMMR tumors all had MLH1 inactivation due to promoter hypermethylation. Unsupervised PCA and cluster analysis demonstrated that normal colon tissue, adenomas, pMMR carcinomas and dMMR carcinomas were all clearly discernable. The majority of miRNAs that were differentially expressed between normal and polyp were also differentially expressed with a similar magnitude in the comparison of normal to both the pMMR and dMMR tumor groups, suggesting a stepwise progression for transformation from normal colon to carcinoma. Among the miRNAs demonstrating the largest fold up- or down-regulated changes (≥4), four novel (miR-31, miR-1, miR-9 and miR-99a) and two previously reported (miR-137 and miR-135b) miRNAs were identified in the normal/adenoma comparison. All but one of these (miR-99a) demonstrated similar expression differences in the two normal/carcinoma comparisons, suggesting that these early tumor changes are important in both the pMMR- and dMMR-derived cancers. The comparison between pMMR and dMMR tumors identified four miRNAs (miR-31, miR-552, miR-592 and miR-224) with statistically significant expression differences (≥2-fold change)

Rethinking Equality in the Global Society

The future of affirmative action, especially in the area of American higher education, has been called into question by the 1996 decision of the U.S. Court of Appeals for the Fifth Circuit in Hopwood v. State of Texas, requiring race-blind admission to state universities in Texas, and the passage of Proposition 209 in California. The seemingly endless American debate on this issue almost entirely has ignored the fact that other countries faced with comparable problems of remedying the effects of past discrimination have developed programs and acquired experience from which Americans might learn. Further, the legal debate has not been adequately informed by the social science disciplines. This conference was intended to expand discussion at a critical moment by introducing these missing perspectives

Transcription restores DNA repair to heterochromatin, determining regional mutation rates in cancer genomes

SummarySomatic mutations in cancer are more frequent in heterochromatic and late-replicating regions of the genome. We report that regional disparities in mutation density are virtually abolished within transcriptionally silent genomic regions of cutaneous squamous cell carcinomas (cSCCs) arising in an XPC−/− background. XPC−/− cells lack global genome nucleotide excision repair (GG-NER), thus establishing differential access of DNA repair machinery within chromatin-rich regions of the genome as the primary cause for the regional disparity. Strikingly, we find that increasing levels of transcription reduce mutation prevalence on both strands of gene bodies embedded within H3K9me3-dense regions, and only to those levels observed in H3K9me3-sparse regions, also in an XPC-dependent manner. Therefore, transcription appears to reduce mutation prevalence specifically by relieving the constraints imposed by chromatin structure on DNA repair. We model this relationship among transcription, chromatin state, and DNA repair, revealing a new, personalized determinant of cancer risk

Optimization of percutaneous biopsy for diagnosis and pretreatment risk assessment of neuroblastoma

BackgroundImage- guided percutaneous core needle biopsy (PCNB) is increasingly utilized to diagnose solid tumors. The objective of this study is to determine whether PCNB is adequate for modern biologic characterization of neuroblastoma.ProcedureA multi- institutional retrospective study was performed by the Pediatric Surgical Oncology Research Collaborative on children with neuroblastoma at 12 institutions over a 3- year period. Data collected included demographics, clinical details, biopsy technique, complications, and adequacy of biopsies for cytogenetic markers utilized by the Children’s Oncology Group for risk stratification.ResultsA total of 243 children were identified with a diagnosis of neuroblastoma: 79 (32.5%) tumor excision at diagnosis, 94 (38.7%) open incisional biopsy (IB), and 70 (28.8%) PCNB. Compared to IB, there was no significant difference in ability to accurately obtain a primary diagnosis by PCNB (95.7% vs 98.9%, P = .314) or determine MYCN copy number (92.4% vs 97.8%, P = .111). The yield for loss of heterozygosity and tumor ploidy was lower with PCNB versus IB (56.1% vs 90.9%, P < .05; and 58.0% vs. 88.5%, P < .05). Complications did not differ between groups (2.9 % vs 3.3%, P = 1.000), though the PCNB group had fewer blood transfusions and lower opioid usage. Efficacy of PCNB was improved for loss of heterozygosity when a pediatric pathologist evaluated the fresh specimen for adequacy.ConclusionsPCNB is a less invasive alternative to open biopsy for primary diagnosis and MYCN oncogene status in patients with neuroblastoma. Our data suggest that PCNB could be optimized for complete genetic analysis by standardized protocols and real- time pathology assessment of specimen quality.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154667/1/pbc28153_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154667/2/pbc28153.pd