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Search Results: 1 - 10 of 2290 matches for " Magdalena Murawska "
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A Two-Stage Joint Model for Nonlinear Longitudinal Response and a Time-to-Event with Application in Transplantation Studies
Magdalena Murawska,Dimitris Rizopoulos,Emmanuel Lesaffre
Journal of Probability and Statistics , 2012, DOI: 10.1155/2012/194194
Abstract: In transplantation studies, often longitudinal measurements are collected for important markers prior to the actual transplantation. Using only the last available measurement as a baseline covariate in a survival model for the time to graft failure discards the whole longitudinal evolution. We propose a two-stage approach to handle this type of data sets using all available information. At the first stage, we summarize the longitudinal information with nonlinear mixed-effects model, and at the second stage, we include the Empirical Bayes estimates of the subject-specific parameters as predictors in the Cox model for the time to allograft failure. To take into account that the estimated subject-specific parameters are included in the model, we use a Monte Carlo approach and sample from the posterior distribution of the random effects given the observed data. Our proposal is exemplified on a study of the impact of renal resistance evolution on the graft survival. 1. Introduction Many medical studies involve analyzing responses together with event history data collected for each patient. A well-known and broadly studied example can be found in AIDS research, where CD4 cell counts taken at different time points are related to the time to death. These data need to be analyzed using a joint modeling approach in order to properly take into account the association between the longitudinal data and the event times. The requirement for a joint modeling approach is twofold. Namely, when focus is on the longitudinal outcome, events cause nonrandom dropout that needs to be accounted for in order to obtain valid inferences. When focus is on the event times, the longitudinal responses cannot be simply included in a relative risk model because they represent the output of an internal time-dependent covariate [1]. In this paper, we focus on a setting that shares some similarities with the standard joint modeling framework described above, but also has important differences. In particular, we are interested in the association between longitudinal responses taken before the actual followup for the time-to-event has been initiated. This setting is frequently encountered in transplantation studies, where patients in the waiting list provide a series of longitudinal outcomes that may be related to events occurring after transplantation. A standard analysis in transplantation studies is to ignore the longitudinal information and use only the last available measurement as a baseline covariate in a model for the allograft survival. It is, however, evident that such an approach
Asymptotic Bayes optimality under sparsity for generally distributed effect sizes under the alternative
Florian Frommlet,Arijit Chakrabarti,Magdalena Murawska,Malgorzata Bogdan
Statistics , 2010,
Abstract: Recent results concerning asymptotic Bayes-optimality under sparsity (ABOS) of multiple testing procedures are extended to fairly generally distributed effect sizes under the alternative. An asymptotic framework is considered where both the number of tests m and the sample size m go to infinity, while the fraction p of true alternatives converges to zero. It is shown that under mild restrictions on the loss function nontrivial asymptotic inference is possible only if n increases to infinity at least at the rate of log m. Based on this assumption precise conditions are given under which the Bonferroni correction with nominal Family Wise Error Rate (FWER) level alpha and the Benjamini- Hochberg procedure (BH) at FDR level alpha are asymptotically optimal. When n is proportional to log m then alpha can remain fixed, whereas when n increases to infinity at a quicker rate, then alpha has to converge to zero roughly like n^(-1/2). Under these conditions the Bonferroni correction is ABOS in case of extreme sparsity, while BH adapts well to the unknown level of sparsity. In the second part of this article these optimality results are carried over to model selection in the context of multiple regression with orthogonal regressors. Several modifications of Bayesian Information Criterion are considered, controlling either FWER or FDR, and conditions are provided under which these selection criteria are ABOS. Finally the performance of these criteria is examined in a brief simulation study.
Stress-Induced PARP Activation Mediates Recruitment of Drosophila Mi-2 to Promote Heat Shock Gene Expression
Magdalena Murawska,Markus Hassler,Renate Renkawitz-Pohl,Andreas Ladurner,Alexander Brehm
PLOS Genetics , 2011, DOI: 10.1371/journal.pgen.1002206
Abstract: Eukaryotic cells respond to genomic and environmental stresses, such as DNA damage and heat shock (HS), with the synthesis of poly-[ADP-ribose] (PAR) at specific chromatin regions, such as DNA breaks or HS genes, by PAR polymerases (PARP). Little is known about the role of this modification during cellular stress responses. We show here that the nucleosome remodeler dMi-2 is recruited to active HS genes in a PARP–dependent manner. dMi-2 binds PAR suggesting that this physical interaction is important for recruitment. Indeed, a dMi-2 mutant unable to bind PAR does not localise to active HS loci in vivo. We have identified several dMi-2 regions which bind PAR independently in vitro, including the chromodomains and regions near the N-terminus containing motifs rich in K and R residues. Moreover, upon HS gene activation, dMi-2 associates with nascent HS gene transcripts, and its catalytic activity is required for efficient transcription and co-transcriptional RNA processing. RNA and PAR compete for dMi-2 binding in vitro, suggesting a two step process for dMi-2 association with active HS genes: initial recruitment to the locus via PAR interaction, followed by binding to nascent RNA transcripts. We suggest that stress-induced chromatin PARylation serves to rapidly attract factors that are required for an efficient and timely transcriptional response.
Dynamic Predictions with Time-Dependent Covariates in Survival Analysis using Joint Modeling and Landmarking
Dimitris Rizopoulos,Magdalena Murawska,Eleni-Rosalina Andrinopoulou,Geert Molenberghs,Johanna J. M. Takkenberg,Emmanuel Lesaffre
Statistics , 2013,
Abstract: A key question in clinical practice is accurate prediction of patient prognosis. To this end, nowadays, physicians have at their disposal a variety of tests and biomarkers to aid them in optimizing medical care. These tests are often performed on a regular basis in order to closely follow the progression of the disease. In this setting it is of medical interest to optimally utilize the recorded information and provide medically-relevant summary measures, such as survival probabilities, that will aid in decision making. In this work we present and compare two statistical techniques that provide dynamically-updated estimates of survival probabilities, namely landmark analysis and joint models for longitudinal and time-to-event data. Special attention is given to the functional form linking the longitudinal and event time processes, and to measures of discrimination and calibration in the context of dynamic prediction.
Changes in the level and quality of life of the population in rural areas in Poland
Anna Murawska
Journal of Agribusiness and Rural Development , 2012,
Abstract: One of the main priorities of the European Union is to strengthen the policy of rural areas in order to improve the level and quality of life. The aim of this study was to provide the level and quality of life in rural areas in Poland and analyse the changes that have occurred in this area since 2003. Coefficients of variation, asymmetry and dynamic factor were calculated utilizing the applied methods. On the basis of the analysis it can be stated that there were significant changes in the equipment in rural areas in the technical infrastructure. Improved housing conditions and increased satisfaction withmaterial and the housing situation were also observed.
Multiple Aspects of ATP-Dependent Nucleosome Translocation by RSC and Mi-2 Are Directed by the Underlying DNA Sequence
Joke J. F. A. van Vugt, Martijn de Jager, Magdalena Murawska, Alexander Brehm, John van Noort, Colin Logie
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006345
Abstract: Background Chromosome structure, DNA metabolic processes and cell type identity can all be affected by changing the positions of nucleosomes along chromosomal DNA, a reaction that is catalysed by SNF2-type ATP-driven chromatin remodelers. Recently it was suggested that in vivo, more than 50% of the nucleosome positions can be predicted simply by DNA sequence, especially within promoter regions. This seemingly contrasts with remodeler induced nucleosome mobility. The ability of remodeling enzymes to mobilise nucleosomes over short DNA distances is well documented. However, the nucleosome translocation processivity along DNA remains elusive. Furthermore, it is unknown what determines the initial direction of movement and how new nucleosome positions are adopted. Methodology/Principal Findings We have used AFM imaging and high resolution PAGE of mononucleosomes on 600 and 2500 bp DNA molecules to analyze ATP-dependent nucleosome repositioning by native and recombinant SNF2-type enzymes. We report that the underlying DNA sequence can control the initial direction of translocation, translocation distance, as well as the new positions adopted by nucleosomes upon enzymatic mobilization. Within a strong nucleosomal positioning sequence both recombinant Drosophila Mi-2 (CHD-type) and native RSC from yeast (SWI/SNF-type) repositioned the nucleosome at 10 bp intervals, which are intrinsic to the positioning sequence. Furthermore, RSC-catalyzed nucleosome translocation was noticeably more efficient when beyond the influence of this sequence. Interestingly, under limiting ATP conditions RSC preferred to position the nucleosome with 20 bp intervals within the positioning sequence, suggesting that native RSC preferentially translocates nucleosomes with 15 to 25 bp DNA steps. Conclusions/Significance Nucleosome repositioning thus appears to be influenced by both remodeler intrinsic and DNA sequence specific properties that interplay to define ATPase-catalyzed repositioning. Here we propose a successive three-step framework consisting of initiation, translocation and release steps to describe SNF2-type enzyme mediated nucleosome translocation along DNA. This conceptual framework helps resolve the apparent paradox between the high abundance of ATP-dependent remodelers per nucleus and the relative success of sequence-based predictions of nucleosome positioning in vivo.
The Drosophila Mi-2 Chromatin-Remodeling Factor Regulates Higher-Order Chromatin Structure and Cohesin Dynamics In Vivo
Barbara Fasulo,Renate Deuring,Magdalena Murawska,Maria Gause,Kristel M. Dorighi,Cheri A. Schaaf,Dale Dorsett,Alexander Brehm,John W. Tamkun
PLOS Genetics , 2012, DOI: 10.1371/journal.pgen.1002878
Abstract: dMi-2 is a highly conserved ATP-dependent chromatin-remodeling factor that regulates transcription and cell fates by altering the structure or positioning of nucleosomes. Here we report an unanticipated role for dMi-2 in the regulation of higher-order chromatin structure in Drosophila. Loss of dMi-2 function causes salivary gland polytene chromosomes to lose their characteristic banding pattern and appear more condensed than normal. Conversely, increased expression of dMi-2 triggers decondensation of polytene chromosomes accompanied by a significant increase in nuclear volume; this effect is relatively rapid and is dependent on the ATPase activity of dMi-2. Live analysis revealed that dMi-2 disrupts interactions between the aligned chromatids of salivary gland polytene chromosomes. dMi-2 and the cohesin complex are enriched at sites of active transcription; fluorescence-recovery after photobleaching (FRAP) assays showed that dMi-2 decreases stable association of cohesin with polytene chromosomes. These findings demonstrate that dMi-2 is an important regulator of both chromosome condensation and cohesin binding in interphase cells.
Journal of Central European Agriculture , 2008,
Abstract: The experimental materials consisted of Koluda White geese, 128 males and 128 females, raised for 12 weeks and fed standard diets ad libitum. Starting from the second week, 28 birds (sex ratio 1:1) were slaughtered at 14-day intervals. Chilled carcasses were dissected into neck, wings, legs, breast and back. Over the experimental period, the body weights of males and females increased on average from 158 g and 112 g on the first day to 5483 g and 5045 g at 12 weeks, respectively. Sexual dimorphism was observed from 4 weeks of age, both in body weight and carcass weight. At the initial growth stage, the percentage content of wings in the carcass increased rapidly (from 5.03% at 2 weeks to 17.44% at 6 weeks), while the proportion of legs decreased (from 40.5% at 2 weeks to 25.55% at 8 weeks). Breast percentage showed a growing tendency (from 19.38% at 2 weeks to 32.70% at 12 weeks), whereas neck and back – a falling one (from 10.13 and 24.96% to 7.73 and 19.61%, respectively).
Nuclear survivin expression is a positive prognostic factor in taxane-platinum-treated ovarian cancer patients
Anna Felisiak-Golabek, Alina Rembiszewska, Iwona K Rzepecka, Lukasz Szafron, Radoslaw Madry, Magdalena Murawska, Tomasz Napiorkowski, Piotr Sobiczewski, Beata Osuch, Jolanta Kupryjanczyk, the Polish Ovarian Cancer Study Group (POCSG)
Journal of Ovarian Research , 2011, DOI: 10.1186/1757-2215-4-20
Abstract: Survivin and TP53 expression was evaluated immunohistochemically in 435 archival samples of ovarian carcinomas (244 patients were treated with platinum/cyclophosphamide-PC/PAC; 191-with taxane-platinum (TP) agents). Univariate and multivariate statistical analyses were performed in patients groups divided according to the administered chemotherapeutic regimen, and in subgroups with and without TP53 accumulation (TP53+ and TP53-, respectively).Nuclear and cytoplasmic survivin expression was observed in 92% and 74% of the carcinomas, respectively. In patients treated with TP, high nuclear survivin expression decreased the risk of disease recurrence and death, and increased the probability of high platinum sensitivity (p < 0.01), but only in the TP53(+) group, and not in the TP53(-) group.It appears that TP53 status determines the clinical importance of nuclear survivin expression in taxane-platinum treated ovarian cancer patients.Recently molecular anticancer therapies have undergone rapid development. Survivin, the smallest member of the family of the protein inhibitors of apoptosis (IAP) [1], is considered to be a potential target for molecular therapy [2]. Target survivin arose from data obtained from cancer cell lines, showing that survivin inhibition contributes to increased tumour response to various anticancer agents [3]. The results of clinical analyses are less consistent, as high survivin expression had been associated with both favourable and unfavourable prognosis [4].Ovarian cancer is the most lethal gynaecological malignancy. In the last decade, taxanes combined with cisplatin or its analogues (TP therapy) have been considered standard first-line treatment for ovarian cancer [5,6]. Although the introduction of taxanes has significantly improved treatment results, still 20% to 30% of the patients fail to achieve complete remission [6-8].Taxanes interact with β-tubulin and increase its polymerisation and stabilisation. In the presence of paclitaxel, cells
Pediatryczna domowa opieka paliatywna w Polsce (2009)
Tomasz Dangel,Ma?gorzata Murawska,Wojciech Marciniak
Medycyna Paliatywna , 2010,
Abstract: Celem badania by a ocena aktualnego stanu pediatrycznej domowej opieki paliatywnej w Polsce.Za pomoc ankiety oceniono roczn liczb pacjentów i zgonów, rozpoznania i wiek chorych.Obliczono wska nik okre laj cy liczb leczonych dzieci na milion mieszkańców. Uzyskano daneo 900 pa cjentach leczonych przez 32 hospicja, w tym o 852 dzieciach i 48 m odych doros ych zeschorzeniami, które rozpocz y si w dzieciństwie. Ludno zamieszkuj ca rejony obj te opiek przez badane hospicja to 93% populacji kraju. Liczba leczonych pacjentów pediatrycznych namilion mieszkańców jest zró nicowana w poszczególnych województwach, najwy sza w województwiepodkarpackim, a najni sza w lubuskim. Nadal w naszym kraju istniej obszary, gdziedomowa opieka paliatywna nad dzie mi nie jest dost pna.
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