Navigating the Rough Waters of Change : The New OhioLINK ETD Service

On January 14, 2013, the OhioLINK community was informed that the Electronic Theses & Dissertations (ETD) service was down for emergency maintenance. Few in the community could have predicted that single event would trigger a tidal wave of changes that ultimately resulted in a complete system rebuild. Panel participants will discuss the situation from their perspectives as OhioLINK ETD stakeholders. Implementing a new consortial system is a tricky undertaking even with adequate time to plan for the development. What additional pressures come into play when an emergency necessitates rapid development and implementation? What is the impact of changing to a new system in the middle of the academic year during the weeks leading up to the community’s busiest ETD season? How will the hundreds of papers submitted but not approved before the system went down be handled? What adjustments will stakeholders need to make in the short term to realize the long term benefit of an improved consortial ETD submission and approval system? What improvements have been realized with the new system? Communication is vitally important during times of transition. What successes and/or failures of communication can be identified in hindsight? How would the situation be different if the Ohio ETD community had not gathered in the summer of 2012 to discuss their needs and desires for a better system that provided a foundation for functional requirements? What are these new functions and how are they working so far? What future enhancements are on the horizon for the new system? The panelists will discuss these and other issues in a session designed for active audience participation

Dietary patterns associated with dental caries in adults in the United States

ObjectivesDental caries experience, which affects 91% of US adults, is a consequence of a carious process influenced by diet. Although individual foods have been implicated, we hypothesized that dietary patterns might be important predictors of caries presence.MethodsWe analysed data from 4467 people ≥18 years old participating in the 2013‐2014 National Health and Nutrition Examination Survey, a nationally representative sample of the US population. Data from 24‐hour dietary recalls were classified into standard food categories and reduced to three dietary patterns using principal components (PCs) analysis. We used regression to model the log‐transformed decayed, missing and filled teeth (DMFT) score and the prevalence of any caries experience by quartiles of PC scores, controlling for potential confounders. Dietary patterns differed by age with respect to dental caries so 18‐30‐year‐olds (n = 1074) and >30‐year‐olds (n = 3393) were analysed separately.ResultsSimilar dietary patterns existed among individuals aged 18‐30 and >30 years, but the prevalence of DMFT score >0 and the median of DMFT was greater in those >30:78.7% (95% CI: 76.1, 81.3) vs 92.6% (95% CI: 91.4, 93.7) and 4 (95% CI: 4, 5) vs 12 DMFT (95% CI: 11, 13), respectively. In those 18‐30, no dietary pattern was associated with greater prevalence or severity of dental caries experience. Among those >30, the prevalence of DMFT>0 was higher by 2% for those in each subsequent quartile of a diet high in sugar‐sweetened beverages and sandwiches (adjusted PR: 1.02, 95% CI: 1.001, 1.03)—thus, the prevalence of dental caries experience was 6% higher among those in the uppermost quartile than in the lowest quartile. For every subsequent quartile in the same pattern, there was a 1.98% higher (95% CI: 0.15, 3.85) DMFT score. However, analysis using the two strongest loading food groups from any of the PCs did not identify any predictors of caries experience.ConclusionsDietary patterns were associated with the prevalence of dental caries experience, with differing findings by age. Although effect sizes were small, the population impact may be substantial. While food groups high in sugar were associated with caries prevalence and severity, associations were more apparent in the context of overall diet. Prospective studies are needed to confirm whether particular dietary patterns are causally related to the development of dental caries.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154279/1/cdoe12509_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154279/2/cdoe12509.pd

Dental Educators’ Perceptions of Educational Learning Domains

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153618/1/jddjde019010.pd

Postpartum Mastitis and Community-acquired Methicillin-resistant Staphylococcus aureus

This single-center, case-control study documents a relative increase in methicillin resistance among 48 cases of Staphylococcus aureus–associated postpartum mastitis during 1998–2005. Of 21 cases with methicillin resistance, 17 (81%) occurred in 2005. Twenty (95%) isolates contained the Staphylococcus cassette chromosome mec type IV gene; this suggests that the increase is due to community-acquired methicillin-resistant Staphylococcus aureus

The present state of research into industrial clusters and districts. Content analysis of material published 1997-2006

[EN] The aim of this work is to help gain a better understanding of the research conducted on territorial agglomerations of firms at a multidisciplinary level. To this end, an analysis was performed of the contents of the most significant scientific literature on economics, management, planning and development, urban studies and geography published over the period 1997-2006. From the results, a database of 142 papers from 43 journals was then elaborated. An analysis of these works reveals the level of development of the main lines of research in this field and, consequently, makes it possible to detect the topics that require greater attention and that can be the object of future research for researchers and academics. The main conclusions include the growing number of studies conducted on the subject in recent years, as well as a greater predominance of empirical research over conceptual work, and the existence of a significant change in the topics or lines of research throughout the period under study. © 2012 Copyright Taylor and Francis Group, LLC.This research was financed by the Spanish Ministry of Education and Science, National R&D & Innovation Plan 2007–2010, under the project entitled “El Distrito Industrial: el impacto del Capital Social sobre la Gestio´n de la Cadena de Suministro” (The Industrial District: the impact of Social Capital on the management of the Supply Chain) (SEJ2007- 62876/ECON).Martinez-Fernandez, M.; Capó Vicedo, J.; Vallet-Bellmunt, T. (2012). The present state of research into industrial clusters and districts. Content analysis of material published 1997-2006. European Planning Studies. 20(2):281-304. doi:10.1080/09654313.2012.650906S28130420

The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that usually affects elderly people. It has a poor prognosis and there are limited therapies. Since epigenetic alterations are associated with IPF, histone deacetylase (HDAC) inhibitors offer a novel therapeutic strategy to address the unmet medical need. This study investigated the potential of romidepsin, an FDA-approved HDAC inhibitor, as an anti-fibrotic treatment and evaluated biomarkers of target engagement that may have utility in future clinical trials. The anti-fibrotic effects of romidepsin were evaluated both in vitro and in vivo together with any harmful effect on alveolar type II cells (ATII). Bronchoalveolar lavage fluid (BALF) from IPF or control donors was analyzed for the presence of lysyl oxidase (LOX). In parallel with an increase in histone acetylation, romidepsin potently inhibited fibroblast proliferation, myofibroblast differentiation and LOX expression. ATII cell numbers and their lamellar bodies were unaffected. In vivo, romidepsin inhibited bleomycin-induced pulmonary fibrosis in association with suppression of LOX expression. LOX was significantly elevated in BALF of IPF patients compared to controls. These data show the anti-fibrotic effects of romidepsin, supporting its potential use as novel treatment for IPF with LOX as a companion biomarker for evaluation of early on-target effects

Dog breed differences in visual communication with humans

Domestic dogs (Canis familiaris) have developed a close relationship with humans through the process of domestication. In human-dog interactions, eye contact is a key element of relationship initiation and maintenance. Previous studies have suggested that canine ability to produce human-directed communicative signals is influenced by domestication history, from wolves to dogs, as well as by recent breed selection for particular working purposes. To test the genetic basis for such abilities in purebred dogs, we examined gazing behavior towards humans using two types of behavioral experiments: the `visual contact task' and the `unsolvable task'. A total of 125 dogs participated in the study. Based on the genetic relatedness among breeds subjects were classified into five breed groups: Ancient, Herding, Hunting, Retriever-Mastiff and Working). We found that it took longer time for Ancient breeds to make an eye-contact with humans, and that they gazed at humans for shorter periods of time than any other breed group in the unsolvable situation. Our findings suggest that spontaneous gaze behavior towards humans is associated with genetic similarity to wolves rather than with recent selective pressure to create particular working breeds

Circulating Biomarkers and Resistance to Endocrine Therapy in Metastatic Breast Cancers: Correlative Results from AZD9496 Oral SERD Phase I Trial.

PURPOSE: Common resistance mechanisms to endocrine therapy (ET) in estrogen receptor (ER)-positive metastatic breast cancers include, among others, ER loss and acquired activating mutations in the ligand-binding domain of the ER gene (ESR1LBDm). ESR1 mutational mediated resistance may be overcome by selective ER degraders (SERD). During the first-in-human study of oral SERD AZD9496, early changes in circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) were explored as potential noninvasive tools, alongside paired tumor biopsies, to assess pharmacodynamics and early efficacy. EXPERIMENTAL DESIGN: CTC were enumerated/phenotyped for ER and Ki67 using CellSearch in serial blood draws. ctDNA was assessed for the most common ESR1LBDm by droplet digital PCR (BioRad). RESULTS: Before starting AZD9496, 11 of 43 (25%) patients had ≥5 CTC/7.5 mL whole blood (WB), none of whom underwent reduction to <5 CTC/7.5 mL WB on C1D15. Five of 11 patients had baseline CTC-ER+, two of whom had CTC-ER+ reduction. CTC-Ki67 status did not change appreciably. Patients with ≥5 CTC/7.5 mL WB before treatment had worse progression-free survival (PFS) than patients with <5 CTC (P = 0.0003). Fourteen of 45 (31%) patients had ESR1LBDm + ctDNA at baseline, five of whom had ≥2 unique mutations. Baseline ESR1LBDm status was not prognostic. Patients with persistently elevated CTC and/or ESR1LBDm + ctDNA at C1D15 had worse PFS than patients who did not (P = 0.0007). CONCLUSIONS: Elevated CTC at baseline was a strong prognostic factor in this cohort. Early on-treatment changes were observed in CTC-ER+ and ESR1LBDm + ctDNA, but not in overall CTC number. Integrating multiple biomarkers in prospective trials may improve outcome prediction and ET resistance mechanisms' identification over a single biomarker

Serial monitoring of genomic alterations in circulating tumor cells of ER-positive/HER2-negative advanced breast cancer: feasibility of precision oncology biomarker detection.

Nearly all estrogen receptor (ER)-positive (POS) metastatic breast cancers become refractory to endocrine (ET) and other therapies, leading to lethal disease presumably due to evolving genomic alterations. Timely monitoring of the molecular events associated with response/progression by serial tissue biopsies is logistically difficult. Use of liquid biopsies, including circulating tumor cells (CTC) and circulating tumor DNA (ctDNA), might provide highly informative, yet easily obtainable, evidence for better precision oncology care. Although ctDNA profiling has been well investigated, the CTC precision oncology genomic landscape and the advantages it may offer over ctDNA in ER-POS breast cancer remain largely unexplored. Whole-blood (WB) specimens were collected at serial time points from patients with advanced ER-POS/HER2-negative (NEG) advanced breast cancer in a phase I trial of AZD9496, an oral selective ER degrader (SERD) ET. Individual CTC were isolated from WB using tandem CellSearch® /DEPArray™ technologies and genomically profiled by targeted single-cell DNA next-generation sequencing (scNGS). High-quality CTC (n = 123) from 12 patients profiled by scNGS showed 100% concordance with ctDNA detection of driver estrogen receptor α (ESR1) mutations. We developed a novel CTC-based framework for precision medicine actionability reporting (MI-CTCseq) that incorporates novel features, such as clonal predominance and zygosity of targetable alterations, both unambiguously identifiable in CTC compared to ctDNA. Thus, we nominated opportunities for targeted therapies in 73% of patients, directed at alterations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), fibroblast growth factor receptor 2 (FGFR2), and KIT proto-oncogene, receptor tyrosine kinase (KIT). Intrapatient, inter-CTC genomic heterogeneity was observed, at times between time points, in subclonal alterations. Our analysis suggests that serial monitoring of the CTC genome is feasible and should enable real-time tracking of tumor evolution during progression, permitting more combination precision medicine interventions

Do bone mineral content and density determine fracture in children? A possible threshold for physical activity

BackgroundRelations between bone parameters, physical exertion, and childhood fractures are complex. We aimed to estimate the associations between fracture history and bone mineral content (BMC) and areal bone mineral density (aBMD) at 7 years of age, by levels of physical activity, as a proxy for trauma frequency.MethodsWe used data collected from 2,261 children of the Generation XXI birth cohort, assembled in 2005/6 in Porto, Portugal. At the age of 7 years (2012/4), fracture history, time spent per week in active play, and sports practice were reported by parents. Subtotal and lumbar spine (LS) BMC and aBMD were measured using whole-body dual-energy X-ray absorptiometry.ResultsBoys and girls in the highest categories of time spent in sports practice or active play generally had higher BMC and aBMD. Among girls, BMC and aBMD were protective of fracture only in the highest quarter of active play (>660 min/week)-odds ratios (OR; 95% confidence interval (95% CI)) for subtotal BMC=0.27 (0.11-0.67), subtotal aBMD=0.18 (0.06-0.49), and LS aBMD=0.41 (0.22-0.75). For boys in the highest quarter of sports practice (>240 min/week), subtotal and LS BMC were protective of fracture-OR=0.39 (0.16-0.98) and 0.51 (0.27-0.96), respectively.ConclusionIn prepubertal children, BMC and aBMD predicted fracture history only in the highest levels of physical activity.info:eu-repo/semantics/publishedVersio