Translating Knowledge of Autism Spectrum Disorders to Action Through Tool Development and Exploration

Translational processes are needed to move research development, methods, and techniques into clinical application. The knowledge to action framework organizes this bench to bedside process through three phases including: research, translation, and institutionalization without being specific to one disease or condition. The overall goal of this research is to bridge gaps in the translational process from assay development to disease detection through a mixed methods approach. A literature review identifies gaps associated with intestinal permeability and autism spectrum disorders. Mining social media related to autism and GI symptoms captures self-reported or observed data, identifies patterns and themes within the data, and works to translate that knowledge into healthcare applications. Development of novel tests can then examine relationships between zonulin levels, haptoglobin genotype, and autism spectrum disorders, and propose a paradigm shift in the use of proteomics and genomic diagnostic testing from clinical diagnosis to pre-symptomatic testing. Although results from this study do not find statistically significant relationships between zonulin and autism spectrum disorders, they do suggest clinical significance and the need to conduct larger studies. The discovery presents a novel approach for measuring intestinal permeability. Qualitative and quantitative methods collaboratively point toward implementation of molecular and data mining techniques in the development and evaluation of early diagnostic tests and interventions. Equally, the two methods working together drive the field forward in design and development to strengthen the outcomes

A Public Policy Analysis of an Allied Health Career Pathway Model at a Local Technical College

Policymakers, philanthropists, and related stakeholders assert that education is “the civil rights issue of our generation” (The White House, n.d). In turn, a career-based business model where “career and technical education encourages employability” (Wilder, 2013) has been implemented, providing readily accessible post-secondary opportunities to address perpetual societal inequality. Many stakeholders perceive the two-year institution as helping bridge the perpetual equity gap by creating access streams needed to acquire good-paying jobs. Because of the diverse socioeconomic student narrative within the Midwestern technical college, a study inquiry was conducted to ascertain the institution’s ability to reproduce the desired results advertised by public policy and determine whether this incremental process “reflects the kinds of things that society ought to be doing to help the marginalized” (Fischer, 2006, p.1) and to address current research gaps. Following Fischer’s (2006) Interpretive Policy Analysis Framework, all research activities were conducted via a sequential explanatory mixed methods design to not only verify empirical and descriptive program data, but also to obtain the participants’ perspectives, sense of agency, and overall outcomes simultaneously with higher level societal goals and values via interpretive analysis. Although each variable’s impact on student success will depend on individual situations, participants specifically discerned systems within the pathway framework inhibiting outcomes. From both the nominal and interpretive research data, maintaining the pathway model as-is potentially impeded social progress and economic stability, especially for the most vulnerable populace. This project provided the chance to appreciate pathway graduate/learner’s persistence even when multiple personal and educational barriers existed while attending school. The complex nature of how this policy affected non-traditional students afforded the opportunity to “not only assess the progress of achieving the (pathway model’s) goal, but the appropriateness of the goal itself” (Fischer, 2006, p. 6) to create or dissuade societal value within the adjacent urban community

Global turnover of histone post-translational modifications and variants in human cells

<p>Abstract</p> <p>Background</p> <p>Post-translational modifications (PTMs) on the N-terminal tails of histones and histone variants regulate distinct transcriptional states and nuclear events. Whereas the functional effects of specific PTMs are the current subject of intense investigation, most studies characterize histone PTMs/variants in a non-temporal fashion and very few studies have reported kinetic information about these histone forms. Previous studies have used radiolabeling, fluorescence microscopy and chromatin immunoprecipitation to determine rates of histone turnover, and have found interesting correlations between increased turnover and increased gene expression. Therefore, histone turnover is an understudied yet potentially important parameter that may contribute to epigenetic regulation. Understanding turnover in the context of histone modifications and sequence variants could provide valuable additional insight into the function of histone replacement.</p> <p>Results</p> <p>In this study, we measured the metabolic rate of labeled isotope incorporation into the histone proteins of HeLa cells by combining stable isotope labeling of amino acids in cell culture (SILAC) pulse experiments with quantitative mass spectrometry-based proteomics. In general, we found that most core histones have similar turnover rates, with the exception of the H2A variants, which exhibit a wider range of rates, potentially consistent with their epigenetic function. In addition, acetylated histones have a significantly faster turnover compared with general histone protein and methylated histones, although these rates vary considerably, depending on the site and overall degree of methylation. Histones containing transcriptionally active marks have been consistently found to have faster turnover rates than histones containing silent marks. Interestingly, the presence of both active and silent marks on the same peptide resulted in a slower turnover rate than either mark alone on that same peptide. Lastly, we observed little difference in the turnover between nearly all modified forms of the H3.1, H3.2 and H3.3 variants, with the notable exception that H3.2K36me2 has a faster turnover than this mark on the other H3 variants.</p> <p>Conclusions</p> <p>Quantitative proteomics provides complementary insight to previous work aimed at quantitatively measuring histone turnover, and our results suggest that turnover rates are dependent upon site-specific post-translational modifications and sequence variants.</p

IU School of Medicine Correctional Medicine Student Outreach Project

Background: This project was founded on the basis that correctional medicine is an important component frequently missing from medical education. Opportunities to participate in medical care within correctional facilities, while concurrently engaging in discussions about disproportionate incarceration of certain populations and mass incarceration as a whole, will cultivate empathetic, socially-engaged, and passionate young physicians. This student organization was formed to facilitate clinical opportunities within correctional facilities and host events that focus on the broader socioeconomic and political context and forms of structural and cultural violence that have contributed to mass incarceration in the United States. Methods: In order to facilitate organizational goals, a relationship was fostered between IUSM and Dr. Kristen Dauss, the Chief Medical Officer of the IDOC. Following affiliation agreements, students may now gain clinical exposure at any facility in the state. Since its creation, IUCM has hosted virtual educational lectures, panels, and journal clubs, in collaboration with other student organizations and scholars in the field. The organization encourages engagement with original research in coordination with faculty advisors. We have also worked with administration to incorporate correctional health topics officially into the curriculum. Conclusions: As physicians who will practice medicine in the country with the highest incarceration rate in the world, having a fundamental understanding of topics related to correctional health, adverse health experiences while incarcerated, and longstanding traumatic effects of incarceration is imperative. IUCM’s goal is to create introductory materials and share resources relating to the socioeconomic and political context which has led to mass incarceration and the deficits in care for currently and formerly incarcerated people. Developing a better understanding of the justice system as well as the emotional, mental, and physical impact incarceration has on patients, and will stimulate interest in engaging with these concepts through research, volunteer work, educational events, and in patient care

The Figure in Art: Selections from the Gettysburg College Collection

The Figure in Art: Selections from the Gettysburg College Collection is the second annual exhibition curated by students enrolled in the Art History Methods class. This exhibition is an exciting academic endeavor and provides an incredible opportunity for engaged learning, research, and curatorial experience. The eleven student curators are Diane Brennan, Rebecca Duffy, Kristy Garcia, Megan Haugh, Dakota Homsey, Molly Lindberg, Kathya Lopez, Kelly Maguire, Kylie McBride, Carolyn McBrady and Erica Schaumberg. Their research presents a multifaceted view of the representation of figures in various art forms from different periods and cultures.https://cupola.gettysburg.edu/artcatalogs/1017/thumbnail.jp

Effect of Shear on Performance and Microbial Ecology of Continuously Stirred Anaerobic Digesters Treating Animal Manure

We Determined the Effect of Different Mixing Intensities on the Performance, Methanogenic Population Dynamics, and Juxtaposition of Syntrophic Microbes in Anaerobic Digesters Treating Cow Manure from a Dairy Farm. Computer Automated Radioactive Particle Tracking in Conjunction with Computational Fluid Dynamics Was Performed to Quantify the Shear Levels Locally. Four Continuously Stirred Anaerobic Digesters Were Operated at Different Mixing Intensities of 1,500, 500, 250, and 50 Revolutions Per Min (RPM) over a 260-Day Period at a Temperature of 34 ± 1°C. Animal Manure at a Volatile Solids (VS) Concentration of 50 G/L Was Fed into the Digesters Daily at Five Different Organic Loading Rates between 0.6 and 3.5 G vs./L Day. the Different Mixing Intensities Had No Effect on the Biogas Production Rates and Yields at Steady-State Conditions. a Methane Yield of 0.241 ± 0.007 L CH 4/g vs. Fed Was Obtained by Pooling the Data of All Four Digesters during Steady-State Periods. However, Digester Performance Was Affected Negatively by Mixing Intensity during Startup of the Digesters, with Lower Biogas Production Rates and Higher Volatile Fatty Acids Concentrations Observed for the 1,500-RPM Digester. Despite Similar Methane Production Yields and Rates, the Acetoclastic Methanogenic Populations Were Different for the High- and Low-Intensity Mixed Digesters with Methanosarcina Spp. and Methanosaeta Concilii as the Predominant Methanogens, Respectively. for All Four Digesters, Epifluorescence Microscopy Revealed Decreasing Microbial Floc Sizes Beginning at Week 4 and Continuing through Week 26 after Which No Microbial Flocs Remained. This Decrease in Size, and Subsequent Loss of Microbial Flocs Did Not, However, Produce Any Long-Term Upsets in Digester Performance. © 2007 Wiley Periodicals, Inc

Pathogenic Role of mTORC1 and mTORC2 in Pulmonary Hypertension.

Concentric lung vascular wall thickening due to enhanced proliferation of pulmonary arterial smooth muscle cells is an important pathological cause for the elevated pulmonary vascular resistance reported in patients with pulmonary arterial hypertension. We identified a differential role of mammalian target of rapamycin (mTOR) complex 1 and complex 2, two functionally distinct mTOR complexes, in the development of pulmonary hypertension (PH). Inhibition of mTOR complex 1 attenuated the development of PH; however, inhibition of mTOR complex 2 caused spontaneous PH, potentially due to up-regulation of platelet-derived growth factor receptors in pulmonary arterial smooth muscle cells, and compromised the therapeutic effect of the mTOR inhibitors on PH. In addition, we describe a promising therapeutic strategy using combination treatment with the mTOR inhibitors and the platelet-derived growth factor receptor inhibitors on PH and right ventricular hypertrophy. The data from this study provide an important mechanism-based perspective for developing novel therapies for patients with pulmonary arterial hypertension and right heart failure

Applying systematic review methods to studies of people’s views: an example from public health research

Methods for systematic reviews are well developed for trials, but not for non-experimental or qualitative research. This paper describes the methods developed for reviewing research on people’s perspectives and experiences (‘‘views’’ studies) alongside trials within a series of reviews on young people’s mental health, physical activity, and healthy eating. Reports of views studies were difficult to locate; could not easily be classified as ‘‘qualitative’’ or ‘‘quantitative’’; and often failed to meet seven basic methodological reporting standards used in a newly developed quality assessment tool. Synthesising views studies required the adaptation of qualitative analysis techniques. The benefits of bringing together views studies in a systematic way included gaining a greater breadth of perspectives and a deeper understanding of public health issues from the point of view of those targeted by interventions. A systematic approach also aided reflection on study methods that may distort, misrepresent, or fail to pick up people’s views. This methodology is likely to create greater opportunities for people’s own perspectives and experiences to inform policies to promote their health

Modifying effect of obesity on the association between sitting time and incident diabetes in post-menopausal women

Objective: To evaluate the association between self-reported daily sitting time and the incidence of type II diabetes in a cohort of postmenopausal women. Design and Methods Women (N = 88,829) without diagnosed diabetes reported the number of hours spent sitting over a typical day. Incident cases of diabetes were identified annually by self-reported initiation of using oral medications or insulin for diabetes over 14.4 years follow-up. Results: Each hour of sitting time was positively associated with increased risk of diabetes (Risk ratio (RR): 1.05; 95% confidence interval (CI): 1.02–1.08]. However, sitting time was only positively associated with incident diabetes in obese women. Obese women reporting sitting 8–11 (RR: 1.08; 95% CI 1.0–1.1), 12–15 (OR: 1.13; 95% CI 1.0–1.2), and ≥16 hours (OR: 1.25; 95% CI 1.0–1.5) hours per day had an increased risk of diabetes compared to women sitting ≤ 7 hours per day. These associations were adjusted for demographics, health conditions, behaviors (smoking, diet and alcohol intake) and family history of diabetes. Time performing moderate to vigorous intensity physical activity did not modify these associations. Conclusion: Time spent sitting was independently associated with increased risk of diabetes diagnosis among obese women— a population already at high risk of the disease