TY - JOUR A1 - Koehler, Friedrich A1 - Koehler, Kerstin A1 - Deckwart, Oliver A1 - Prescher, Sandra A1 - Wegscheider, Karl A1 - Winkler, Sebastian A1 - Vettorazzi, Eik A1 - Polze, Andreas A1 - Stangl, Karl A1 - Hartmann, Oliver A1 - Marx, Almuth A1 - Neuhaus, Petra A1 - Scherf, Michael A1 - Kirwan, Bridget-Anne A1 - Anker, Stefan D. T1 - Telemedical Interventional Management in Heart Failure II (TIM-HF2), a randomised, controlled trial investigating the impact of telemedicine on unplanned cardiovascular hospitalisations and mortality in heart failure patients BT - study design and description of the intervention JF - European Journal of Heart Failure N2 - Background Heart failure (HF) is a complex, chronic condition that is associated with debilitating symptoms, all of which necessitate close follow-up by health care providers. Lack of disease monitoring may result in increased mortality and more frequent hospital readmissions for decompensated HF. Remote patient management (RPM) in this patient population may help to detect early signs and symptoms of cardiac decompensation, thus enabling a prompt initiation of the appropriate treatment and care before a manifestation of HF decompensation. Objective The objective of the present article is to describe the design of a new trial investigating the impact of RPM on unplanned cardiovascular hospitalisations and mortality in HF patients. Methods The TIM-HF2 trial is designed as a prospective, randomised, controlled, parallel group, open (with randomisation concealment), multicentre trial with pragmatic elements introduced for data collection. Eligible patients with HF are randomised (1:1) to either RPM + usual care or to usual care only and are followed for 12 months. The primary outcome is the percentage of days lost due to unplanned cardiovascular hospitalisations or all-cause death. The main secondary outcomes are all-cause and cardiovascular mortality. Conclusion The TIM-HF2 trial will provide important prospective data on the potential beneficial effect of telemedical monitoring and RPM on unplanned cardiovascular hospitalisations and mortality in HF patients. KW - Chronic heart failure KW - Telemonitoring KW - Remote patient management KW - Hospitalisation Y1 - 2018 U6 - https://doi.org/10.1002/ejhf.1300 SN - 1388-9842 SN - 1879-0844 VL - 20 IS - 10 SP - 1485 EP - 1493 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Melcher, Ralph A1 - Hartmann, Elena A1 - Zopf, Waltraud A1 - Herterich, Sabine A1 - Wilke, Philipp A1 - Mueller, Ludwig A1 - Rosler, Eduard A1 - Kudlich, Theodor A1 - Al-Taie, Oliver A1 - Rosenwald, Andreas A1 - Katzenberger, Tiemo A1 - Scholtka, Bettina A1 - Seibold, Stefan A1 - Rogoll, Dorothee A1 - Scheppach, Wolfgang A1 - Scheurlen, Michael A1 - Luehrs, Hardi T1 - LOH and copy neutral LOH (cnLOH) act as alternative mechanism in sporadic colorectal cancers with chromosomal and microsatellite instability JF - Carcinogenesis : a comprehensive survey N2 - Background and aims. Tumor suppressor genes are often located in frequently deleted chromosomal regions of colorectal cancers (CRCs). In contrast to microsatellite stable (MSS) tumors, only few loss of heterozygosity (LOH) studies were performed in microsatellite instable (MSI) tumors, because MSI carcinomas are generally considered to be chromosomally stable and classical LOH studies are not feasible due to MSI. The single nucleotide polymorphism (SNP) array technique enables LOH studies also in MSI CRC. The aim of our study was to analyse tissue from MSI and MSS CRC for the existence of (frequently) deleted chromosomal regions and tumor suppressor genes located therein. Methods and results. We analyzed tissues from 32 sporadic CRCs and their corresponding normal mucosa (16 MSS and 16 MSI tumors) by means of 50K SNP array analysis. MSS tumors displayed chromosomal instability that resulted in multiple deleted (LOH) and amplified regions and led to the identification of MTUS1 (8p22) as a candidate tumor suppressor gene in this region. Although the MSI tumors were chromosomally stable, we found several copy neutral LOHs (cnLOH) in the MSI tumors; these appear to be instrumental in the inactivation of the tumor suppressor gene hMLH1 and a gene located in chromosomal region 6pter-p22. Discussion. Our results suggest that in addition to classical LOH, cnLOH is an important mutational event in relation to the carcinogenesis of MSS and MSI tumors, causing the inactivation of a tumor suppressor gene without copy number alteration of the respective region; this is crucial for the development of MSI tumors and for some chromosomal regions in MSS tumors. Y1 - 2011 U6 - https://doi.org/10.1093/carcin/bgr011 SN - 0143-3334 VL - 32 IS - 4 SP - 636 EP - 642 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Burleigh, J. Gordon A1 - Bansal, Mukul S. A1 - Eulenstein, Oliver A1 - Hartmann, Stefanie A1 - Wehe, Andre A1 - Vision, Todd J. T1 - Genome-Scale Phylogenetics inferring the plant tree of life from 18,896 gene trees JF - Systematic biology N2 - Phylogenetic analyses using genome-scale data sets must confront incongruence among gene trees, which in plants is exacerbated by frequent gene duplications and losses. Gene tree parsimony (GTP) is a phylogenetic optimization criterion in which a species tree that minimizes the number of gene duplications induced among a set of gene trees is selected. The run time performance of previous implementations has limited its use on large-scale data sets. We used new software that incorporates recent algorithmic advances to examine the performance of GTP on a plant data set consisting of 18,896 gene trees containing 510,922 protein sequences from 136 plant taxa (giving a combined alignment length of >2.9 million characters). The relationships inferred from the GTP analysis were largely consistent with previous large-scale studies of backbone plant phylogeny and resolved some controversial nodes. The placement of taxa that were present in few gene trees generally varied the most among GTP bootstrap replicates. Excluding these taxa either before or after the GTP analysis revealed high levels of phylogenetic support across plants. The analyses supported magnoliids sister to a eudicot + monocot clade and did not support the eurosid I and II clades. This study presents a nuclear genomic perspective on the broad-scale phylogenic relationships among plants, and it demonstrates that nuclear genes with a history of duplication and loss can be phylogenetically informative for resolving the plant tree of life. KW - Gene tree-species tree reconciliation KW - gene tree parsimony KW - plant phylogeny KW - phylogenomics Y1 - 2011 U6 - https://doi.org/10.1093/sysbio/syq072 SN - 1063-5157 VL - 60 IS - 2 SP - 117 EP - 125 PB - Oxford Univ. Press CY - Oxford ER -