Filter and export

Publications

959 Publications visible to you, out of a total of 959
Secretory phospholipase A(2)-IIA and cardiovascular disease: a mendelian randomization study
Genetical Statistics and Systems Biology

Abstract (Expand)

OBJECTIVES\backslashr\backslashnThis study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease.\backslashr\backslashnBACKGROUND\backslashr\backslashnHigher … circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA2 inhibitor (varespladib) was stopped prematurely for lack of efficacy.\backslashr\backslashnMETHODS\backslashr\backslashnWe conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA2-IIA isoenzyme, as an instrumental variable.\backslashr\backslashnRESULTS\backslashr\backslashnPLA2G2A rs11573156 C allele associated with lower circulating sPLA2-IIA mass (38% to 44%) and sPLA2 enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA2-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE.\backslashr\backslashnCONCLUSIONS\backslashr\backslashnReducing sPLA2-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.

Authors: Michael V. Holmes, Tabassome Simon, Holly J. Exeter, Lasse Folkersen, Folkert W. Asselbergs, Montse Guardiola, Jackie A. Cooper, Jutta Palmen, Jaroslav A. Hubacek, Kathryn F. Carruthers, Benjamin D. Horne, Kimberly D. Brunisholz, Jessica L. Mega, Erik P A van Iperen, Mingyao Li, Maarten Leusink, Stella Trompet, Jeffrey J W Verschuren, G. Kees Hovingh, Abbas Dehghan, Christopher P. Nelson, Salma Kotti, Nicolas Danchin, Markus Scholz, Christiane L. Haase, Dietrich Rothenbacher, Daniel I. Swerdlow, Karoline B. Kuchenbaecker, Eleonora Staines-Urias, Anuj Goel, Ferdinand van ’t Hooft, Karl Gertow, Ulf de Faire, Andrie G. Panayiotou, Elena Tremoli, Damiano Baldassarre, Fabrizio Veglia, Lesca Miriam Holdt, Frank Beutner, Ron T. Gansevoort, Gerjan J. Navis, Irene Mateo Leach, Lutz P. Breitling, Hermann Brenner, Joachim Thiery, Dhayana Dallmeier, Anders Franco-Cereceda, Jolanda M A Boer, Jeffrey W. Stephens, Marten H. Hofker, Alain Tedgui, Albert Hofman, André G. Uitterlinden, Vera Adamkova, Jan Pitha, N. Charlotte Onland-Moret, Maarten J. Cramer, Hendrik M. Nathoe, Wilko Spiering, Olaf H. Klungel, Meena Kumari, Peter H. Whincup, David A. Morrow, Peter S. Braund, Alistair S. Hall, Anders G. Olsson, Pieter A. Doevendans, Mieke D. Trip, Martin D. Tobin, Anders Hamsten, Hugh Watkins, Wolfgang Koenig, Andrew N. Nicolaides, Daniel Teupser, Ian N M Day, John F. Carlquist, Tom R. Gaunt, Ian Ford, Naveed Sattar, Sotirios Tsimikas, Gregory G. Schwartz, Debbie A. Lawlor, Richard W. Morris, Manjinder S. Sandhu, Rudolf Poledne, Anke H Maitland-van der Zee, Kay-Tee Khaw, Brendan J. Keating, Pim van der Harst, Jackie F. Price, Shamir R. Mehta, Salim Yusuf, Jaqueline C M Witteman, Oscar H. Franco, J. Wouter Jukema, Peter de Knijff, Anne Tybjaerg-Hansen, Daniel J. Rader, Martin Farrall, Nilesh J. Samani, Mika Kivimaki, Keith A A Fox, Steve E. Humphries, Jeffrey L. Anderson, S. Matthijs Boekholdt, Tom M. Palmer, Per Eriksson, Guillaume Paré, Aroon D. Hingorani, Marc S. Sabatine, Ziad Mallat, Juan P. Casas, Philippa J. Talmud

Date Published: 1st Nov 2013

Publication Type: Journal article

Prevalence of minor depression in elderly persons with and without mild cognitive impairment: a systematic review.
LIFE Adult

Abstract (Expand)

BACKGROUND: Minor depression (MinD) and mild cognitive impairment (MCI) are common disorders in late life that often coexist. The aim of the present review is to demonstrate prevalence rates of minor … depression in older patients with and without MCI. METHODS: Electronic database searches were performed through Medline, ISI Web of Knowledge, Psycinfo, and Cochrane library. Two independent reviewers extracted the original studies based on inclusion criteria: representative study population aged 55 and older, diagnostics of MinD according to DSM. Data on prevalence rates, risk factors, comorbidity and health care usage were analyzed. RESULTS: Point prevalence for MinD is higher in medical settings (median 14.4%) than in the community-based settings (median 10.4%) and primary care patients (median 7.7%). Although minor depression is rarely investigated in elderly persons with MCI, nearly 20% of patients with MCI seem to suffer from MinD. No data was found on the prevalence of MCI in patients with MinD. Risk factors associated with MinD include female gender, history of cerebrovascular diseases, generalized anxiety disorder, loneliness, and long-term institutional care. LIMITATIONS: Methodological differences of included studies resulted in a broad range of prevalence rates. No data is shown regarding the prevalence of MCI in MinD group due to insufficient evidence. CONCLUSIONS: Our review indicates that MinD is frequent in elderly population. MCI among those subjects has not been sufficiently investigated. Future studies based on clinical structured interviews should be performed in longitudinal design in order to differentiate late-life depression from progressive MCI or early manifestation of Alzheimer's disease.

Authors: M. Polyakova, N. Sonnabend, C. Sander, R. Mergl, M. L. Schroeter, J. Schroeder, P. Schonknecht

Date Published: 10th Oct 2013

Publication Type: Not specified

Human Diseases: mental depression

The pore size of PLGA bone implants determines the de novo formation of bone tissue in tibial head defects in rats
Genetical Statistics and Systems Biology

Abstract (Expand)

PURPOSE\backslashr\backslashnThe influence of the pore size of biodegradable poly(lactic-co-glycolic acid) scaffolds on bone regeneration was investigated.\backslashr\backslashnMETHODS\backslashr\backslashnCylindrical … poly(lactic-co-glycolic acid) scaffolds were implanted into a defect in the tibial head of rats. Pore sizes of 100-300, 300-500, and 500-710 \textgreekmm were tested and compared to untreated defects as control. Two and four weeks after implantation, the specimens were explanted and defect regeneration and de novo extracellular matrix generation were investigated by MRI, quantitative solid-state NMR, and mass spectrometry.\backslashr\backslashnRESULTS\backslashr\backslashnThe pore size of the scaffolds had a pronounced influence on the quantity of the extracellular matrix synthesized in the graft; most collagen was synthesized within the first 2 weeks of implantation, while the amount of hydroxyapatite increased in the second 2 weeks. After 4 weeks, the scaffolds contained large quantities of newly formed lamellar bone while the control defects were filled by inhomogenous woven bone. Best results were obtained for scaffolds of a pore size of 300-500 \textgreekmm.\backslashr\backslashnCONCLUSION\backslashr\backslashnOur analysis showed that the structure and dynamics of the regenerated extracellular matrix was very similar to that of the native bone, suggesting that biomineralization was significantly enhanced by the choice of the most appropriate implant material.

Authors: Anja Penk, Yvonne Förster, Holger A. Scheidt, Ariane Nimptsch, Michael C. Hacker, Michaela Schulz-Siegmund, Peter Ahnert, Jürgen Schiller, Stefan Rammelt, Daniel Huster

Date Published: 1st Oct 2013

Publication Type: Journal article

Behandlung der Patienten mit einem Venenastverschluss in Abhängigkeit von der Verschlussdauer
Genetical Statistics and Systems Biology

Abstract (Expand)

PURPOSE\backslashr\backslashnThe aim of this study was to evaluate the effects of intravitreal treatment with bevacizumab (IVB) compared with triamcinolone (IVT) in patients with macular edema due to … branch retinal vein occlusion (BRVO) depending on the duration of BRVO.\backslashr\backslashnMETHODS\backslashr\backslashnA total of 65 BRVO patients were divided into 2 subgroups: group 1 with early treatment (≤ 3 months since onset of BRVO) and group 2 with late treatment (\textgreater 3 months since onset). For the two groups IVB was injected into 17 eyes as early (IVB1) and into 18 eyes as late (IVB2) treatment. For comparison IVT was injected into 14 eyes as early (IVT1) and into 16 eyes as late (IVT2) treatment. Best corrected visual acuity (BCVA) and central retinal thickness (CRT) were analyzed at baseline, 1, 3 and 6 months after treatment.\backslashr\backslashnRESULTS\backslashr\backslashnIn both subgroups a significant improvement of BCVA and CRwas observed. After 6 months, for patients with early treatment, IVB1 showed better results than IVT1 (BCVA: p = 0.008, CRT: p = 0.021). In the late treatment no significant differences between IVT2 and IVB2 were found.\backslashr\backslashnCONCLUSIONS\backslashr\backslashnBevacizumab and triamcinolone significantly improved BCVA and CRT in patients with BRVO. The best BCVA was found if bevacizumab was used as early treatment. In the late treatment no significant differences between bevacizumab and triamcinolone were observed.

Authors: Matus Rehak, E. Spies, Markus Scholz, Peter Wiedemann

Date Published: 1st Oct 2013

Publication Type: Journal article

The comprehensive IT-Infrastructure for epidemiological Research in LIFE
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

Introduction LIFE is a large epidemiological study aiming at causes of common civilization diseases including adiposity, dementia, and depression. Participants of the study are probands and patients. … Probands are randomly selected and invited from the set of Leipzig (Germany) inhabitants while patients with known diseases are recruited from several local hospitals. The management of these participants, their invitation and contact after successful attendance as well as the support of nearly all ambulance processes requires a complex ambulance management. Each participant is examined by a set of investigation instruments including interviews, questionnaires, device-specific investigations, specimen extrac- tions and analyses. This necessitates a complex management of the participantspecific examination program but also specific input forms and systems allowing to capture administrative (measurement and process environment or specific set-ups) and scientific data. Additionally, the taken and prepared specimens need to be labeled and registered from which participant they stem and in which fridge or bio-tank they are stored. At the end, all captured data from ambu- lance management, investigation instruments and laboratory analyses need to be integrated before they can be analyzed. These complex processes and requirements necessitate a comprehensive IT-infrastructure. Methods Our IT-infrastructure modularly consists of several software applications. A main application is responsible for the complex participant and ambulance man- agement. The participant management cope with selected participant data and contact information. To protect participant’s privacy, a participant identifier (PID) is created for each participant that is associated to all data which is managed and captured in the following. In ambulance management, each participant is associated with a predefined investigation program. This investigation program is represented in our systems by a tracking card that is available as print-out and electronically. The electronic version of tracking cards is utilized by two software applications, the Assessment Battery and the CryoLab. The former system coordinates the input of scientific data into online input forms. The input forms are designed in the open source system LimeSurvey. Moreover, the Assessment Battery is used to monitor the input process, i.e., it shows which investigations are already completed and which of them are still to do. The Cryolab system registers and tracks all taken specimens and is used to annotate extraction and specific preparation processes, e.g., for DNA isolation. Moreover, it tracks specimen storage in fridges and bio-tanks. A central component is the metadata repository collecting metadata from ambulance management and data input systems. It is the base for the integra- tion of relevant scientific data into a central research database. The integration follows a mapping-based approach. The research database makes raw data and special pre-computations called derivatives available for later data analysis. Results & Discussion We designed and implemented a complex and comprehensive IT-infrastructure for the epidemiological research in LIFE. This infrastructure consists of several software applications which are loosely coupled over specified interfaces. Most of the software applications are new implementations; only for capturing scientific data external software application are applied.

Authors: Toralf Kirsten, A. Kiel, M. Kleinert, R. Speer, M. Rühle, Hans Binder, Markus Löffler

Date Published: 30th Sep 2013

Publication Type: Not specified

Curation-DB: Curating Scientific Data in LIFE
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

Introduction LIFE is a epidemiological study aiming at discovering causes of common disorders as well as therapy and diagnostic possibilities. It applies a huge set (currently more then 400) of complex … instruments including different kinds of interviews, questionnaires, and technically founded investigations on thousands of Leipzig inhabitants. Correlations in data, e.g., between diseases on the one hand and a combination of life conditions on the other requires high quality data. Data errors affect this data quality. However, avoiding every error is nearly impossible. Therefore, the captured data routinely needs to be validated and revised (curated) in case of error. Methods From the data-perspective, we differentiate between two main types of data errors, syntax or format errors and semantic errors. Syntax errors mostly occur when the data needs to be converted to change its data type, e.g., from text to number or from text to date/time fields. This is often the case when data is captured as text by the data input system but should be centrally managed and analyzed in a different format. Hence, the data conversion is only successful when the input data contains the data in the right format. Data conversion is applied when the data is transfered from data input systems to the central research database collecting all captured data in an integrated and harmonized form. Corrupted data that cannot be converted to the target data type is replaced by a missing value (also called null value, nil etc.). The definition of a default value is not sufficient since the default usually depends on the corresponding question or measurement input field and can strain analysis results when they are not concerned. Moreover, the definition process for every question/input field would be to time-consuming. Semantic errors are much harder to detect than syntax errors. Typically, they are semantically implausible outliers or are part of other artefacts, e.g.,when data of two input fields is mixed up. Currently, we let the detection of semantic errors to a epidemiological quality analysis that is performed by several statisticians. Conversely, syntax errors can be easily technically detected; they are logged when they occur in the process of transferring data from data input systems to the central research database. With respect to both types of errors, syntax and semantic errors, we designed and implemented a software application called Curation-DB allowing to curate (adapt and change) data. In particular, the system lists the logged syntax errors occurring during the data conversion step daily at night. A user can adapt the current input value by specifying a new (target) value for a listed syntax problem. With this specification, the corresponding input value is replaced by the specified value before the next conversion step is started. This specification process can be iteratively applied for a corresponding input value when the syntax problem is not solved by the current specification. The semantic errors need to be first detected separately. Then, a user can specify value changes replacing an existing value with the new specified one. Results & Discussion The Curation-DB application is already in use. Currently, selected quality managers routinely check the listed syntax errors. There are currently more than 2000 of such errors curated. In near future, we will extend this software to manage rules validating research data semantically to automatically detect obvious semantic errors.

Authors: J. Wagner, A. Kiel, Toralf Kirsten

Date Published: 30th Sep 2013

Publication Type: Not specified

Long-term survival in primary glioblastoma with versus without isocitrate dehydrogenase mutations.
GGN - German Glioma Network

Abstract (Expand)

PURPOSE: The determinants of long-term survival in glioblastoma have remained largely obscure. Isocitrate dehydrogenase (IDH) 1 or 2 mutations are common in World Health Organization (WHO) grades II … and III gliomas, but rare in primary glioblastomas, and associated with longer survival. EXPERIMENTAL DESIGN: We compared clinical and molecular characteristics of 69 patients with centrally confirmed glioblastoma and survival >36 months (LTS-36), including 33 patients surviving >60 months (LTS-60), with 257 patients surviving <36 months. MGMT promoter methylation, 1p/19q codeletions, EGFR amplification, TP53 mutations, and IDH1/2 mutations were determined by standard techniques. RESULTS: The rate of IDH1/2 mutations in LTS-36 patients was 34% (23 of 67 patients) as opposed to 4.3% in controls (11 of 257 patients). Long-term survivors with IDH1/2-mutant glioblastomas were younger, had almost no EGFR amplifications, but exhibited more often 1p/19q codeletions and TP53 mutations than LTS patients with IDH1/2 wild-type glioblastomas. Long-term survivors with IDH1/2 wild-type showed no distinguishing features from other patients with IDH1/2 wild-type glioblastomas except for a higher rate of MGMT promoter methylation. Similarly, among 11 patients with IDH1/2-mutant glioblastomas without long-term survival, the only difference to IDH1/2-mutant long-term survivors was less-frequent MGMT promoter methylation. Compared with LTS-36 patients, LTS-60 patients had less frequently TP53 mutations and radiotherapy alone as initial treatment. CONCLUSIONS: IDH1/2 mutations define a subgroup of tumors of LTS patients that exhibit molecular characteristics of WHO grade II/III gliomas and secondary glioblastomas. Determinants of LTS with IDH1/2 wild-type glioblastomas, which exhibit typical molecular features of primary glioblastomas, beyond MGMT promoter methylation, remain to be identified.

Authors: C. Hartmann, B. Hentschel, M. Simon, M. Westphal, G. Schackert, J. C. Tonn, M. Loeffler, G. Reifenberger, T. Pietsch, A. von Deimling, M. Weller

Date Published: 15th Sep 2013

Publication Type: Not specified

Human Diseases: glioblastoma multiforme

Navigate

Health Atlas - Local Data Hub/Leipzig

The Health Atlas - Local Data Hub/Leipzig is an alliance of medical ontologists, medical systems biologists and clinical trials groups to design and implement a multi-functional and quality-assured atlas. It provides models, data and metadata on specific use cases from medical research fields.

Registered Repository

re3data.org Badge
Powered by
 (v.1.13.0-master)
Health Atlas | Funding and Programmes | Credits | Terms & Conditions | Privacy Policy | Imprint
Copyright © 2008 - 2021 The University of Manchester and HITS gGmbH
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig

By continuing to use this site you agree to the use of cookies