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Search Results: 1 - 10 of 31040 matches for " Thomas Ried "
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Comparing biomarkers and proteomic fingerprints for classification studies  [PDF]
Brian T. Luke, Jack R. Collins, Jens K. Habermann, DaRue A. Prieto, Timothy D. Veenstra, Thomas Ried
Journal of Biomedical Science and Engineering (JBiSE) , 2013, DOI: 10.4236/jbise.2013.64057

Early disease detection is extremely important in the treatment and prognosis of many diseases, especially cancer. Often, proteomic fingerprints and a pattern recognition algorithm are used to classify the pathological condition of a given individual. It has been argued that accurate classification of the existing data implies an underlying biological significance. Two fingerprint-based classifiers, decision tree and medoid classification algorithm, and a biomarker-based classifier were examined using a published dataset of mass spectral peaks from 81 healthy individuals and 78 individuals with benign prostate hyperplasia (BPH). For all three methods, classifiers were constructed using the original data and the data after permuting the labels of the samples (BPH and healthy). The fingerprint-based classifiers produced accurate results for the original data, though the peaks used in a given classifier depended upon which samples were placed in the training set. Accurate results were also obtained for the dataset with permuted labels. In contrast, only three unique peaks were identified as putative biomarkers, producing a small number of reasonably accurate biomarker-based classifiers. The dataset with permuted labels was poorly classified. Since fingerprint-based classifiers accurately classified the dataset with permuted labels, the argument for biological significance from a fingerprint-based classifier must be questioned.

Acute kidney injury in septua- and octogenarians after cardiac surgery
Michael Ried, Thomas Puehler, Assad Haneya, Christof Schmid, Claudius Diez
BMC Cardiovascular Disorders , 2011, DOI: 10.1186/1471-2261-11-52
Abstract: A retrospective study between 01/2006 and 08/2009 with 299 octogenarians, who were matched for gender and surgical procedure to 299 septuagenarians at a university hospital. Primary endpoint was AKI after surgery as proposed by the RIFLE definition (Risk, Injury, Failure, Loss, End-stage kidney disease). Secondary endpoint was 30-day mortality. Perioperative mortality was predicted with the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE).Octogenarians significantly had a mean higher logistic EuroSCORE compared to septuagenarians (13.2% versus 8.5%; p < 0.001) and a higher proportion of patients with an estimated glomerular filtration rate (eGFR) < 60 ml × min-1 × 1.73 m-2. In contrast, septuagenarians showed a slightly higher median body mass index (28 kg × m-2 versus 26 kg × m-2) and were more frequently active smoker at time of surgery (6.4% versus 1.6%, p < 0.001). Acute kidney injury and failure developed in 21.7% of septuagenarians and in 21.4% of octogenarians, whereas more than 30% of patients were at risk for AKI (30% and 36.3%, respectively). Greater degrees of AKI were associated with a stepwise increase in risk for death, renal replacement therapy and prolonged stays at the intensive care unit and at the hospital in both age groups, but without differences between them. Overall 30-day mortality was 6% in septuagenarians and 7.7% in octogenarians (p = 0.52).The RIFLE classification provided accurate risk assessment for 30-day mortality and fair discriminatory power.The RIFLE criteria allow identifying patients with AKI after cardiac surgery. The high incidence of AKI in septua- and octogenarians after cardiac surgery should prompt the use of RIFLE criteria to identify patients at risk and should stimulate institutional measures that target AKI as a quality improvement initiative for patients at advanced age.Recent estimates showed that significant proportions of the United States and Western European population are greater than 6
On the economic impact of a regional management of multidrug-resistant bacteria
Ried, Walter
GMS Krankenhaushygiene Interdisziplin?r , 2011,
Abstract: The increasing number of people who are colonized or infected with multidrug-resistant bacteria imposes a high economic burden on society which includes the negative impact on health status as an intangible cost. An economic analysis leads to the conclusion that currently too little is done to prevent or control infections. The reasons include insufficient incentives for health care providers, a lack of reliable data on both the prevalence and the effects of infection, and a lack of coordination among the different branches of the health care sector. A regional management of multidrugresistant bacteria which does not focus on a single branch but rather on the health care sector overall can achieve a substantial reduction in the number of infected people and of the associated economic cost for society.
Garlic, Chocolate, or Tomatoes for (Pre-) Hypertension?
Ried K
Journal für Hypertonie , 2011,
Abstract: Aged garlic extract, dark chocolate, or lycopene-rich tomato products have been linked with blood pressure-lowering properties in hypertensive people. There is consistent evidence for garlic supplements, in particular in the form of Kyolic aged garlic extract, to be effective in lowering blood pressure comparable to first-line standard antihypertensive medication. Dark chocolate appears to be beneficial for blood pressure reduction as well, albeit to a lesser extent than Kyolic . Lycopene in tomato extract has a protective effect on serum cholesterol similar to low-dose statins, and may also be beneficial for lowering blood pressure in hypertensive people.
Effect of garlic on blood pressure: A systematic review and meta-analysis
Karin Ried, Oliver R Frank, Nigel P Stocks, Peter Fakler, Thomas Sullivan
BMC Cardiovascular Disorders , 2008, DOI: 10.1186/1471-2261-8-13
Abstract: We searched the Medline and Embase databases for studies published between 1955 and October 2007. Randomised controlled trials with true placebo groups, using garlic-only preparations, and reporting mean systolic and/or diastolic blood pressure (SBP/DBP) and standard deviations were included in the meta-analysis. We also conducted subgroup meta-analysis by baseline blood pressure (hypertensive/normotensive), for the first time. Meta-regression analysis was performed to test the associations between blood pressure outcomes and duration of treatment, dosage, and blood pressure at start of treatment.Eleven of 25 studies included in the systematic review were suitable for meta-analysis. Meta-analysis of all studies showed a mean decrease of 4.6 ± 2.8 mm Hg for SBP in the garlic group compared to placebo (n = 10; p = 0.001), while the mean decrease in the hypertensive subgroup was 8.4 ± 2.8 mm Hg for SBP (n = 4; p < 0.001), and 7.3 ± 1.5 mm Hg for DBP (n = 3; p < 0.001). Regression analysis revealed a significant association between blood pressure at the start of the intervention and the level of blood pressure reduction (SBP: R = 0.057; p = 0.03; DBP: R = -0.315; p = 0.02).Our meta-analysis suggests that garlic preparations are superior to placebo in reducing blood pressure in individuals with hypertension.Hypertension (systolic blood pressure (SBP) ≥ 140 mm Hg; diastolic blood pressure (DBP) ≥ 90 mm Hg) is a known risk factor for cardiovascular morbidity and mortality, affecting an estimated 1 billion individuals worldwide [1]. Recently updated guidelines for the treatment of high blood pressure stress the importance of preventive strategies, and recommend extending the management of blood pressure to include pre-hypertensive individuals (SBP 120–139/DBP 80–89 mm Hg) [1]. Primary management should include relevant lifestyle modifications such as increased exercise, weight loss and dietary changes which could incorporate dietary supplementation.Garlic (Allium sativum) h
Evaluating annotations of an Agilent expression chip suggests that many features cannot be interpreted
E Michael Gertz, Kundan Sengupta, Michael J Difilippantonio, Thomas Ried, Alejandro A Sch?ffer
BMC Genomics , 2009, DOI: 10.1186/1471-2164-10-566
Abstract: Out of 42683 reporters, we found that 25505 (60%) passed all our tests and are considered "fully valid". 9964 (23%) reporters did not have a meaningful identifier, mapped to the wrong chromosome, or did not pass basic alignment tests preventing us from correlating the expression values of these reporters with a unique annotated human gene. The remaining 7214 (17%) reporters could be associated with either a unique gene or a unique intergenic location, but could not be mapped to a transcript in RefSeq. The 7214 reporters are further partitioned into three different levels of validity.Expression array studies should evaluate the annotations of reporters and remove those reporters that have suspect annotations. This evaluation can be done systematically and semi-automatically, but one must recognize that data sources are frequently updated leading to slightly changing validation results over time.Agilent-014850 Whole Human Genome Microarray 4 × 44K G4112F consists of 43,376 oligonucleotides 60 nucleotides in length, most of which are annotated as corresponding to the sequence of a known or predicted human gene, along with a number of probes that function as controls. Agilent supplies an annotation file for the array. The file provides the sequence of each oligonucleotide, its position on the NCBI human reference assembly, and the gene and transcript putatively associated with it. The annotation file states "This multi-pack (4 × 44K) formatted microarray represents a compiled view of the human genome as it is understood today." From here on, we refer to each oligonucleotide as a "reporter", rather than the more commonly used terms oligo, probe, or 60-mer, to indicate that each oligonucleotide is supposed to "report" the expression of a single gene unambiguously. Some reporters unambiguously distinguish between transcripts of a single gene, but others hybridize with more than one transcript of the same gene.We sought to validate the annotations against the current inform
Does chocolate reduce blood pressure? A meta-analysis
Karin Ried, Thomas Sullivan, Peter Fakler, Oliver R Frank, Nigel P Stocks
BMC Medicine , 2010, DOI: 10.1186/1741-7015-8-39
Abstract: We searched Medline, Cochrane and international trial registries between 1955 and 2009 for randomised controlled trials investigating the effect of cocoa as food or drink compared with placebo on systolic and diastolic blood pressure (SBP/DBP) for a minimum duration of 2 weeks. We conducted random effects meta-analysis of all studies fitting the inclusion criteria, as well as subgroup analysis by baseline blood pressure (hypertensive/normotensive). Meta-regression analysis explored the association between type of treatment, dosage, duration or baseline blood pressure and blood pressure outcome. Statistical significance was set at P < 0.05.Fifteen trial arms of 13 assessed studies met the inclusion criteria. Pooled meta-analysis of all trials revealed a significant blood pressure-reducing effect of cocoa-chocolate compared with control (mean BP change ± SE: SBP: -3.2 ± 1.9 mmHg, P = 0.001; DBP: -2.0 ± 1.3 mmHg, P = 0.003). However, subgroup meta-analysis was significant only for the hypertensive or prehypertensive subgroups (SBP: -5.0 ± 3.0 mmHg; P = 0.0009; DBP: -2.7 ± 2.2 mm Hg, P = 0.01), while BP was not significantly reduced in the normotensive subgroups (SBP: -1.6 ± 2.3 mmHg, P = 0.17; DBP: -1.3 ± 1.6 mmHg, P = 0.12). Nine trials used chocolate containing 50% to 70% cocoa compared with white chocolate or other cocoa-free controls, while six trials compared high- with low-flavanol cocoa products. Daily flavanol dosages ranged from 30 mg to 1000 mg in the active treatment groups, and interventions ran for 2 to 18 weeks. Meta-regression analysis found study design and type of control to be borderline significant but possibly indirect predictors for blood pressure outcome.Our meta-analysis suggests that dark chocolate is superior to placebo in reducing systolic hypertension or diastolic prehypertension. Flavanol-rich chocolate did not significantly reduce mean blood pressure below 140 mmHg systolic or 80 mmHg diastolic.Flavanol-rich chocolate and cocoa products hav
CKAP2 Ensures Chromosomal Stability by Maintaining the Integrity of Microtubule Nucleation Sites
Chanelle M. Case, Dan L. Sackett, Danny Wangsa, Tatiana Karpova, James G. McNally, Thomas Ried, Jordi Camps
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0064575
Abstract: Integrity of the microtubule spindle apparatus and intact cell division checkpoints are essential to ensure the fidelity of distributing chromosomes into daughter cells. Cytoskeleton-associated protein 2, CKAP2, is a microtubule-associated protein that localizes to spindle poles and aids in microtubule stabilization, but the exact function and mechanism of action are poorly understood. In the present study, we utilized RNA interference to determine the extent to which the expression of CKAP2 plays a role in chromosome segregation. CKAP2-depleted cells showed a significant increase of multipolar mitoses and other spindle pole defects. Notably, when interrogated for microtubule nucleation capacity, CKAP2-depleted cells showed a very unusual phenotype as early as two minutes after release from mitotic block, consisting of dispersal of newly polymerized microtubule filaments through the entire chromatin region, creating a cage-like structure. Nevertheless, spindle poles were formed after one hour of mitotic release suggesting that centrosome-mediated nucleation remained dominant. Finally, we showed that suppression of CKAP2 resulted in a higher incidence of merotelic attachments, anaphase lagging, and polyploidy. Based on these results, we conclude that CKAP2 is involved in the maintenance of microtubule nucleation sites, focusing microtubule minus ends to the spindle poles in early mitosis, and is implicated in maintaining genome stability.
Algorithms to Model Single Gene, Single Chromosome, and Whole Genome Copy Number Changes Jointly in Tumor Phylogenetics
Salim Akhter Chowdhury,Stanley E. Shackney,Kerstin Heselmeyer-Haddad,Thomas Ried,Alejandro A. Sch?ffer,Russell Schwartz
PLOS Computational Biology , 2014, DOI: doi/10.1371/journal.pcbi.1003740
Abstract: We present methods to construct phylogenetic models of tumor progression at the cellular level that include copy number changes at the scale of single genes, entire chromosomes, and the whole genome. The methods are designed for data collected by fluorescence in situ hybridization (FISH), an experimental technique especially well suited to characterizing intratumor heterogeneity using counts of probes to genetic regions frequently gained or lost in tumor development. Here, we develop new provably optimal methods for computing an edit distance between the copy number states of two cells given evolution by copy number changes of single probes, all probes on a chromosome, or all probes in the genome. We then apply this theory to develop a practical heuristic algorithm, implemented in publicly available software, for inferring tumor phylogenies on data from potentially hundreds of single cells by this evolutionary model. We demonstrate and validate the methods on simulated data and published FISH data from cervical cancers and breast cancers. Our computational experiments show that the new model and algorithm lead to more parsimonious trees than prior methods for single-tumor phylogenetics and to improved performance on various classification tasks, such as distinguishing primary tumors from metastases obtained from the same patient population.
Inflammation-Mediated Genetic and Epigenetic Alterations Drive Cancer Development in the Neighboring Epithelium upon Stromal Abrogation of TGF-β Signaling
B. R. Achyut,David A. Bader,Ana I. Robles,Darawalee Wangsa,Curtis C. Harris,Thomas Ried,Li Yang
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003251
Abstract: Deletion of tumor suppressor genes in stromal fibroblasts induces epithelial cancer development, suggesting an important role of stroma in epithelial homoeostasis. However, the underlying mechanisms remain to be elucidated. Here we report that deletion of the gene encoding TGFβ receptor 2 (Tgfbr2) in the stromal fibroblasts (Tgfbr2fspKO) induces inflammation and significant DNA damage in the neighboring epithelia of the forestomach. This results in loss or down-regulation of cyclin-dependent kinase inhibitors p15, p16, and p21, which contribute to the development of invasive squamous cell carcinoma (SCC). Anti-inflammation treatment restored p21 expression, delayed tumorigenesis, and increased survival of Tgfbr2fspKO mice. Our data demonstrate for the first time that inflammation is a critical player in the epigenetic silencing of p21 in tumor progression. Examination of human esophageal SCC showed a down-regulation of TGFβ receptor 2 (TβRII) in the stromal fibroblasts, as well as increased inflammation, DNA damage, and loss or decreased p15/p16 expression. Our study suggests anti-inflammation may be a new therapeutic option in treating human SCCs with down-regulation of TβRII in the stroma.
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