Common target genes of palatal and gingival fibroblasts for EMD: the microarray approach.

BACKGROUND AND OBJECTIVE Connective tissue grafts are frequently applied, together with Emdogain(®) , for root coverage. However, it is unknown whether fibroblasts from the gingiva and from the palate respond similarly to Emdogain. The aim of this study was therefore to evaluate the effect of Emdogain(®) on fibroblasts from palatal and gingival connective tissue using a genome-wide microarray approach. MATERIAL AND METHODS Human palatal and gingival fibroblasts were exposed to Emdogain(®) and RNA was subjected to microarray analysis followed by gene ontology screening with Database for Annotation, Visualization and Integrated Discovery functional annotation clustering, Kyoto Encyclopedia of Genes and Genomes pathway analysis and the Search Tool for the Retrieval of Interacting Genes/Proteins functional protein association network. Microarray results were confirmed by quantitative RT-PCR analysis. RESULTS The transcription levels of 106 genes were up-/down-regulated by at least five-fold in both gingival and palatal fibroblasts upon exposure to Emdogain(®) . Gene ontology screening assigned the respective genes into 118 biological processes, six cellular components, eight molecular functions and five pathways. Among the striking patterns observed were the changing expression of ligands targeting the transforming growth factor-beta and gp130 receptor family as well as the transition of mesenchymal epithelial cells. Moreover, Emdogain(®) caused changes in expression of receptors for chemokines, lipids and hormones, and for transcription factors such as SMAD3, peroxisome proliferator-activated receptor gamma and those of the ETS family. CONCLUSION The present data suggest that Emdogain(®) causes substantial alterations in gene expression, with similar patterns observed in palatal and gingival fibroblasts.

Temporal change in prevalence and complications of uveitis associated with juvenile idiopathic arthritis:data from a cross-sectional analysis of a prospective nationwide study

OBJECTIVES To analyse the nationwide prevalence of uveitis in JIA and its complications over a whole decade. METHODS We conducted a prospective, observational and cross-sectional study including all JIA patients from a National Paediatric Rheumatological Database (NPRD) with a uveitis add-on module in Germany (2002-2013). Temporal changes in uveitis prevalence, related secondary complications and anti-inflammatory medication were evaluated. RESULTS A total of 60 centres including 18,555 JIA patients (mean 3,863 patients/year, SD=837) were documented in the NPRD between 2002 and 2013. The mean age of the patients was 11.4±4.6 years, their mean disease duration 4.4±3.7 years. Among them, 66.9% were female and 51.7% ANA positive. Patients' mean age at arthritis onset was 6.9±4.5 years. Treatment rates with synthetic and biological DMARDs increased during the observation period (sDMARD: 39.8% to 47.2%, bDMARD: 3.3% to 21.8%). Uveitis prevalence decreased significantly from 2002 to 2013 (13.0% to 11.6%, OR = 0.98, p=0.015). The prevalence of secondary uveitis complications also decreased significantly between 2002 and 2013 (33.6% to 23.9%, OR=0.94, p<0.001). Among the complications, the most common ones were posterior synechiae, cataract and band keratopathy. A significant increase in achieving uveitis inactivity was observed at 30.6% in 2002 and 65.3% in 2013 (OR=1.15, p<0.001). CONCLUSIONS Uveitis prevalence and complications significantly decreased between 2002 and 2013. This may be associated with a more frequent use of DMARDs.

Range of Motion of the Upper Extremity in a Healthy Pediatric Population: Introduction to Normative Data.

Objective In the pediatric population traumatic injuries of the upper extremity are common. After therapy a decision has to be made if the mobility of the joint lies within a normal range. The purpose of this study was to give an introduction to normative data. We investigate if there is a significant difference in the range of motion (ROM) between male and female probands and furthermore, if an effect of the age can be detected. Methods We performed an institutional review board-approved study of healthy girls and boys aged between 2 and 16 years without any medical history of an upper extremity fracture. We investigated the active ROM of the elbow, wrist, metacarpophalangeal, and interphalangeal joints. Furthermore, age, handedness, weight, and height were recorded. A total of 171 adolescents with a mean age of 10.6 years were included and separated into four cohorts by age: 2 to 5, 6 to 10, 11 to 13, and 14 to 16 years. Results We found significant differences between the genders in the age group from 11 to 13 years for the flexion of the elbow, the pronation, the flexion of the interphalangeal joint of the thumb, as well as the flexion of the metacarpophalangeal joints of digitus II to V. Furthermore, a significant difference in the same joints except from the elbow flexion could be demonstrated between the genders. Conclusion Our study contributes normative data for upper extremity ROM in the pediatric population and presents a gender-related difference in certain joints. Clinical Relevance Normative data for the ROM of upper extremity joints in children is helpful for the evaluation of pediatric orthopedic patients and provides the framework for therapeutic resolution. Since a great number of traumatic injuries in children affect the upper extremity, this information may help the physician to estimate the impact of the injury and decide on the therapeutic management.

Detection of Malnutrition in Patients Undergoing Maintenance Haemodialysis: A Quantitative Data Analysis on 12 Parameters

Background Protein-energy-malnutrition (PEM) is common in people with end stage kidney disease (ESKD) undergoing maintenance haemodialysis (MHD) and correlates strongly with mortality. To this day, there is no gold standard for detecting PEM in patients on MHD. Aim of Study The aim of this study was to evaluate if Nutritional Risk Screening 2002 (NRS-2002), handgrip strength measurement, mid-upper arm muscle area (MUAMA), triceps skin fold measurement (TSF), serum albumin, normalised protein catabolic rate (nPCR), Kt/V and eKt/V, dry body weight, body mass index (BMI), age and time since start on MHD are relevant for assessing PEM in patients on MHD. Methods The predictive value of the selected parameters on mortality and mortality or weight loss of more than 5% was assessed. Quantitative data analysis of the 12 parameters in the same patients on MHD in autumn 2009 (n = 64) and spring 2011 (n = 40) with paired statistical analysis and multivariate logistic regression analysis was performed. Results Paired data analysis showed significant reduction of dry body weight, BMI and nPCR. Kt/Vtot did not change, eKt/v and hand grip strength measurements were significantly higher in spring 2011. No changes were detected in TSF, serum albumin, NRS-2002 and MUAMA. Serum albumin was shown to be the only predictor of death and of the combined endpoint “death or weight loss of more than 5%”. Conclusion We now screen patients biannually for serum albumin, nPCR, Kt/V, handgrip measurement of the shunt-free arm, dry body weight, age and time since initiation of MHD.

Index Tracking Using Data-Mining Techniques and Mixed-Binary Linear Programming

Index tracking has become one of the most common strategies in asset management. The index-tracking problem consists of constructing a portfolio that replicates the future performance of an index by including only a subset of the index constituents in the portfolio. Finding the most representative subset is challenging when the number of stocks in the index is large. We introduce a new three-stage approach that at first identifies promising subsets by employing data-mining techniques, then determines the stock weights in the subsets using mixed-binary linear programming, and finally evaluates the subsets based on cross validation. The best subset is returned as the tracking portfolio. Our approach outperforms state-of-the-art methods in terms of out-of-sample performance and running times.

Fertility preservation for non-medical reasons: controversial, but increasingly common.

BACKGROUND Fertility-preserving measures for women are increasingly being performed for non-medical reasons in Germany. This is now a controversial matter. METHODS The authors searched the PubMed database for pertinent publications on the basis of their clinical and scientific experience and evaluated relevant data from the registry of the German FertiPROTEKT network (www.fertiprotekt. com). The various fertility-preserving measures that are available are described and critically discussed. RESULTS In most cases, the creation of a fertility reserve currently involves the cryopreservation of unfertilized oocytes, rather than of ovarian tissue. Most of the women who decide to undergo this procedure are over 35 years old. According to data from the FertiPROTEKT registry, most such procedures carried out in the years 2012 and 2013 involved a single stimulation cycle. The theoretical probability of childbirth per stimulation is 40% in women under age 35 and 30% in women aged 35 to 39. If the oocytes are kept for use at a later date, rather than at once, the maternal risk is higher, because the mother is older during pregnancy. The risk to the child may be higher as well because of the need for in vitro fertilization (IVF). Pregnancy over age 40 often leads to complications such as gestational diabetes and pre-eclampsia. IVF may be associated with a higher risk of epigenetic abnormalities. Ethicists have upheld women's reproductive freedom while pointing out that so-called social freezing merely postpones social problems, rather than solving them. CONCLUSION Fertility preservation for non-medical reasons should be critically discussed, and decisions should be made on a case-by-case basis.

The Effect of Incidental Consolidation on Management and Outcomes in COPD Exacerbations: Data from the European COPD Audit

OBJECTIVE There is controversy regarding the significance of radiological consolidation in the context of COPD exacerbation (eCOPD). While some studies into eCOPD exclude these cases, consolidation is a common feature of eCOPD admissions in real practice. This study aims to address the question of whether consolidation in eCOPD is a distinct clinical phenotype with implications for management decisions and outcomes. PATIENTS AND METHODS The European COPD Audit was carried out in 384 hospitals from 13 European countries between 2010 and 2011 to analyze guideline adherence in eCOPD. In this analysis, admissions were split according to the presence or not of consolidation on the admission chest radiograph. Groups were compared in terms of clinical and epidemiological features, existing treatment, clinical care utilized and mortality. RESULTS 14,111 cases were included comprising 2,714 (19.2%) with consolidation and 11,397 (80.8%) without. The risk of radiographic consolidation increased with age, female gender, cardiovascular diseases, having had two or more admissions in the previous year, and sputum color change. Previous treatment with inhaled steroids was not associated. Patients with radiographic consolidation were significantly more likely to receive antibiotics, oxygen and non-invasive ventilation during the admission and had a lower survival from admission to 90-day follow-up. CONCLUSIONS Patients admitted for COPD exacerbation who have radiological consolidation have a more severe illness course, are treated more intensively by clinicians and have a poorer prognosis. We recommend that these patients be considered a distinct subset in COPD exacerbation.

Addressing missing participant outcome data in dental clinical trials

Missing outcome data are common in clinical trials and despite a well-designed study protocol, some of the randomized participants may leave the trial early without providing any or all of the data, or may be excluded after randomization. Premature discontinuation causes loss of information, potentially resulting in attrition bias leading to problems during interpretation of trial findings. The causes of information loss in a trial, known as mechanisms of missingness, may influence the credibility of the trial results. Analysis of trials with missing outcome data should ideally be handled with intention to treat (ITT) rather than per protocol (PP) analysis. However, true ITT analysis requires appropriate assumptions and imputation of missing data. Using a worked example from a published dental study, we highlight the key issues associated with missing outcome data in clinical trials, describe the most recognized approaches to handling missing outcome data, and explain the principles of ITT and PP analysis.

Shape model, reference system definition, and cartographic mapping standards for comet 67P/Churyumov-Gerasimenko Stereo-photogrammetric analysis of Rosetta/OSIRIS image data

We analyzed more than 200 OSIRIS NAC images with a pixel scale of 0.9-2.4 m/pixel of comet 67P/Churyumov-Gerasimenko (67P) that have been acquired from onboard the Rosetta spacecraft in August and September 2014 using stereo-photogrammetric methods (SPG). We derived improved spacecraft position and pointing data for the OSIRIS images and a high-resolution shape model that consists of about 16 million facets (2 m horizontal sampling) and a typical vertical accuracy at the decimeter scale. From this model, we derive a volume for the northern hemisphere of 9.35 km(3) +/- 0.1 km(3). With the assumption of a homogeneous density distribution and taking into account the current uncertainty of the position of the comet's center-of-mass, we extrapolated this value to an overall volume of 18.7 km(3) +/- 1.2 km(3), and, with a current best estimate of 1.0 X 10(13) kg for the mass, we derive a bulk density of 535 kg/m(3) +/- 35 kg/m(3). Furthermore, we used SPG methods to analyze the rotational elements of 67P. The rotational period for August and September 2014 was determined to be 12.4041 +/- 0.0004 h. For the orientation of the rotational axis (z-axis of the body-fixed reference frame) we derived a precession model with a half-cone angle of 0.14 degrees, a cone center position at 69.54 degrees/64.11 degrees (RA/Dec J2000 equatorial coordinates), and a precession period of 10.7 days. For the definition of zero longitude (x-axis orientation), we finally selected the boulder-like Cheops feature on the big lobe of 67P and fixed its spherical coordinates to 142.35 degrees right-hand-rule eastern longitude and -0.28 degrees latitude. This completes the definition of the new Cheops reference frame for 67P. Finally, we defined cartographic mapping standards for common use and combined analyses of scientific results that have been obtained not only within the OSIRIS team, but also within other groups of the Rosetta mission.

Public Commons for Geospatial Data: A Conceptual Model

A wide variety of spatial data collection efforts are ongoing throughout local, state and federal agencies, private firms and non-profit organizations. Each effort is established for a different purpose but organizations and individuals often collect and maintain the same or similar information. The United States federal government has undertaken many initiatives such as the National Spatial Data Infrastructure, the National Map and Geospatial One-Stop to reduce duplicative spatial data collection and promote the coordinated use, sharing, and dissemination of spatial data nationwide. A key premise in most of these initiatives is that no national government will be able to gather and maintain more than a small percentage of the geographic data that users want and desire. Thus, national initiatives depend typically on the cooperation of those already gathering spatial data and those using GIs to meet specific needs to help construct and maintain these spatial data infrastructures and geo-libraries for their nations (Onsrud 2001). Some of the impediments to widespread spatial data sharing are well known from directly asking GIs data producers why they are not currently involved in creating datasets that are of common or compatible formats, documenting their datasets in a standardized metadata format or making their datasets more readily available to others through Data Clearinghouses or geo-libraries. The research described in this thesis addresses the impediments to wide-scale spatial data sharing faced by GIs data producers and explores a new conceptual data-sharing approach, the Public Commons for Geospatial Data, that supports user-friendly metadata creation, open access licenses, archival services and documentation of parent lineage of the contributors and value- adders of digital spatial data sets.

Digital repository implementation: a toolbox for streamlined success

Purpose – The purpose of this paper is to describe the tools and strategies that were employed by C/W MARS to successfully develop and implement the Digital Treasures digital repository. Design/methodology/approach – This paper outlines the planning and subsequent technical issues that arise when implementing a digitization project on the scale of the large, multi-type, automated library network. Workflow solutions addressed include synchronous online metadata record submissions from multiple library sources and the delivery of collection-level use statistics to participating library administrators. The importance of standards-based descriptive metadata and the role of project collaboration are also discussed. Findings – From the time of its initial planning, the Digital Treasures repository was fully implemented in six months. The discernable and statistically quantified online discovery and access of actual digital objects greatly assisted libraries unsure of their own staffing costs/benefits to join the repository. Originality/value – This case study may serve as a possible example of initial planning, workflow and final implementation strategies for new repositories in both the general and library consortium environment. Keywords – Digital repositories, Library networks, Data management. Paper type – Case study

Gastric cancer survival amongst Hispanics- A Hispanic paradox? A case series study using the SEER 1973--2005 data registry

Stomach cancer is the fourth most common cancer in the world, and ranked 16th in the US in 2008. The age-adjusted rates among Hispanics were 2.8 times that of non-Hispanic Whites in 1998-2002. In spite of that, previous research has found that Hispanics with non-cardia adenocarcinoma of the stomach have a slightly better survival than non-Hispanic Whites. However, such previous research did not include a comparison with African-Americans, and it was limited to data released for the years 1973-2000 in the nine original Surveillance, Epidemiology, and End Results Cancer Registries. This finding was interpreted as related to the Hispanic Paradox, a phenomenon that refers to the fact that Hispanics in the USA tend to paradoxically have substantially better health than other ethnic groups in spite of what their aggregate socio-economic indicators would predict. We extended such research to the SEER 17 Registry, 1973-2005, with varying years of diagnosis per registry, and compared the survival of non-cardia adenocarcinoma of the stomach according to ethnicity (Hispanics, non-Hispanic Whites and African-Americans), while controlling for age, gender, marital status, stage of disease and treatment using Cox regression survival analysis. We found that Hispanic ethnicity by itself did not confer an advantage on survival from non-cardia adenocarcinoma of the stomach, but that being born abroad was independently associated with the apparent 'Hispanic Paradox' previously reported, and that such advantage was seen among foreign born persons across all race/ethnic groups.^

Clinical and economic outcomes of serious postoperative infections following resection of common respiratory and gastrointestinal solid tumors

Unlike infections occurring during periods of chemotherapy-induced neutropenia, postoperative infections in patients with solid malignancy remain largely understudied. The purpose of this population-based study was to evaluate the clinical and economic burden, as well as the relationship of hospital surgical volume and outcomes associated with serious postoperative infection (SPI) – i.e., bacteremia/sepsis, pneumonia, and wound infection – following resection of common solid tumors.^ From the Texas Discharge Data Research File, we identified all Texas residents who underwent resection of cancer of the lung, esophagus, stomach, pancreas, colon, or rectum between 2002 and 2006. From their billing records, we identified ICD-9 codes indicating SPI and also subsequent SPI-related readmissions occurring within 30 days of surgery. Random-effects logistic regression was used to calculate the impact of SPI on mortality, as well as the association between surgical volume and SPI, adjusting for case-mix, hospital characteristics, and clustering of multiple surgical admissions within the same patient and patients within the same hospital. Excess bed days and costs were calculated by subtracting values for patients without infections from those with infections computed using multilevel mixed-effects generalized linear model by fitting a gamma distribution to the data using log link.^ Serious postoperative infection occurred following 9.4% of the 37,582 eligible tumor resections and was independently associated with an 11-fold increase in the odds of in-hospital mortality (95% Confidence Interval [95% CI], 6.7-18.5, P < 0.001). Patients with SPI required 6.3 additional hospital days (95% CI, 6.1 - 6.5) at an incremental cost of $16,396 (95% CI, $15,927–$16,875). There was a significant trend toward lower overall rates of SPI with higher surgical volume (P=0.037). ^ Due to the substantial morbidity, mortality, and excess costs associated with SPI following solid tumor resections and given that, under current reimbursement practices, most of this heavy burden is borne by acute care providers, it is imperative for hospitals to identify more effective prophylactic measures, so that these potentially preventable infections and their associated expenditures can be averted. Additional volume-outcomes research is also needed to identify infection prevention processes that can be transferred from higher- to lower-volume providers.^

Functional data analysis approaches for genotype-phenotype association studies from next-generation sequencing

Next-generation DNA sequencing platforms can effectively detect the entire spectrum of genomic variation and is emerging to be a major tool for systematic exploration of the universe of variants and interactions in the entire genome. However, the data produced by next-generation sequencing technologies will suffer from three basic problems: sequence errors, assembly errors, and missing data. Current statistical methods for genetic analysis are well suited for detecting the association of common variants, but are less suitable to rare variants. This raises great challenge for sequence-based genetic studies of complex diseases.^ This research dissertation utilized genome continuum model as a general principle, and stochastic calculus and functional data analysis as tools for developing novel and powerful statistical methods for next generation of association studies of both qualitative and quantitative traits in the context of sequencing data, which finally lead to shifting the paradigm of association analysis from the current locus-by-locus analysis to collectively analyzing genome regions.^ In this project, the functional principal component (FPC) methods coupled with high-dimensional data reduction techniques will be used to develop novel and powerful methods for testing the associations of the entire spectrum of genetic variation within a segment of genome or a gene regardless of whether the variants are common or rare.^ The classical quantitative genetics suffer from high type I error rates and low power for rare variants. To overcome these limitations for resequencing data, this project used functional linear models with scalar response to develop statistics for identifying quantitative trait loci (QTLs) for both common and rare variants. To illustrate their applications, the functional linear models were applied to five quantitative traits in Framingham heart studies. ^ This project proposed a novel concept of gene-gene co-association in which a gene or a genomic region is taken as a unit of association analysis and used stochastic calculus to develop a unified framework for testing the association of multiple genes or genomic regions for both common and rare alleles. The proposed methods were applied to gene-gene co-association analysis of psoriasis in two independent GWAS datasets which led to discovery of networks significantly associated with psoriasis.^

Early identification of symptomatic aortic stenosis using echocardiographic data

Background: Heart failure (CHF) is the most frequent and prognostically severe symptom of aortic stenosis (AS), and the most common indication for surgery. The mainstay of treatment for AS is aortic valve replacement (AVR), and the main indication for an AVR is development of symptomatic disease. ACC/AHA guidelines define severe AS as an aortic valve area (AVA) ≤1cm², but there is little data correlating echocardiogram AVA with the onset of symptomatic CHF. We evaluated the risk of developing CHF with progressively decreasing echocardiographic AVA. We also compared echocardiographic AVA with Jet velocity (V2) and indexed AVA (AVAI) to assess the best predictor of development of symptomatic CHF.^ Methods and Results: This retrospective cohort study evaluated 518 patients with asymptomatic moderate or severe AS from a single community based cardiology practice. A total of 925 echocardiograms were performed over an 11-year period. Each echocardiogram was correlated with concurrent clinical assessments while the investigator was blinded to the echocardiogram severity of AS. The Cox Proportional hazards model was used to analyze the relationship between AVA and the development of CHF. The median age of patients at entry was 76.1 years, with 54% males. A total of 116 patients (21.8%) developed new onset CHF during follow-up. Compared to patients with AVA >1.0cm², patients with lower AVA had an exponentially increasing risk of developing CHF for each 0.2cm² decrement in AVA, becoming statistically significant only at an AVA less than 0.8 cm². Also, compared to V2 and AVAI, AVA added more information to assessing risk for development of CHF (p=0.041). ^ Conclusion: In patients with normal or mildly impaired LVEF, the risk of CHF rises exponentially with decreasing valve area and becomes statistically significant after AVA falls below 0.8cm². AVA is a better predictor of CHF when compared to V2 or AVAI.^