bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the Prediction of Winter Precipitation and Temperature over the Continental United States: Role of the ENSO State in Developing Multimodel Combinations
Authors: Devineni Naresh , Sankarasubramanian A. 
Published: December 2009

AbstractRecent research into seasonal climate prediction has focused on combining multiple atmospheric general circulation models (GCMs) to develop multimodel ensembles. A new approach to combining multiple GCMs is proposed by analyzing the skill levels of candidate models contingent on the relevant predictor(s) state. To demonstrate this approach, historical simulations of winter (December–February, DJF) precipitation and temperature from seven GCMs were combined by evaluating their skill—represented by mean square error (MSE)—over similar predictor (DJF Niño-3.4) conditions. The MSE estimates are converted into weights for each GCM for developing multimodel tercile probabilities. A total of six multimodel schemes are considered that include combinations based on pooling of ensembles as well as on the long-term skill of the models. To ensure the improved skill exhibited by the multimodel scheme is statistically significant, rigorous hypothesis tests were performed comparing the skill of multimodels with each individual model’s skill. The multimodel combination contingent on Niño-3.4 shows improved skill particularly for regions whose winter precipitation and temperature exhibit significant correlation with Niño-3.4. Analyses of these weights also show that the proposed multimodel combination methodology assigns higher weights for GCMs and lesser weights for climatology during El Niño and La Niña conditions. On the other hand, because of the limited skill of GCMs during neutral Niño-3.4 conditions, the methodology assigns higher weights for climatology resulting in improved skill from the multimodel combinations. Thus, analyzing GCMs’ skill contingent on the relevant predictor state provides an alternate approach for multimodel combinations such that years with limited skill could be replaced with climatology.
Improving Seasonal Forecast Skill of North American Surface Air Temperature in Fall Using a Postprocessing Method
Authors: Jia XiaoJing , Lin Hai , Derome Jacques 
Published: December 2009

Abstract
A statistical postprocessing approach is applied to seasonal forecasts of surface air temperatures (SAT) over North America in fall, when the original uncalibrated predictions have little skill. The data used are ensemble-mean seasonal forecasts from four atmospheric general circulation models (GCMs) in the Canadian Historical Forecasting Project (HFP2) during the period 1969–2001. The statistical postprocessing uses the relationship between the predicted 500-hPa geopotential height (Z500) and the observed SAT to calibrate the SAT forecasts. The dimensions of the predicted Z500 fields are reduced to three modes with fixed spatial structures but time-dependent amplitudes. The latter are obtained through a singular value decomposition (SVD) analysis linking the variability of the ensemble-mean predicted Z500 to the tropical Pacific sea surface temperatures (SSTs). Results show that the postprocessing significantly improves the predictive skill of North American SAT in fall. The distributions of the SAT temporal standard deviation and the skill of the postprocessed ensemble forecasts are consistent among the GCMs, indicating that the approach is effective in reducing the model-dependent part of the errors associated with GCMs.
A Mass-Conserving Quasi-Monotonic Filter for Use in Semi-Lagrangian Models
Authors: Kaas Eigil , Nielsen Joakim R. 
Published: December 2009

Abstract
A new mass-conserving and quasi-monotonic antidiffusive filter has been designed for application in semi-Lagrangian-type models. The filter redistributes local mass such that the resulting values are brought closer to target values. The target values, in turn, are specified from a nonlinear antidiffusion of the original nonfiltered forecast. To achieve quasi-monotonicity, the target values are constrained to a certain interval, defined by the minimum and maximum value of the upstream grid cells surrounding the semi-Lagrangian departure point. Allowing a less local reorganization of mass the filter can be made fully monotonic and positive definite.
The filter has been applied to the recently developed locally mass-conserving semi-Lagrangian (LMCSL) scheme. A number of idealized test simulations in one and two dimensions demonstrates that the combined scheme is stable and quasi monotonic. Furthermore, the accuracy is enhanced considerably as compared to the original LMCSL scheme, particularly near sharp changes in gradients. When tested in the geophysical flow environment of a shallow-water model, the proposed filter, in practice, ensures monotonicity and positive definiteness without generation of spurious features. In its present implementation the computational cost of the combined scheme is approximately twice the cost of the LMCSL scheme.
Results and factors influencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: impact of center size: an analysis on behalf of the Acute Leukemia and Pediatric Disease Working Parties of the European Blood and Marrow Transplant group
Authors: Klingebiel Thomas , Cornish Jacqueline , Labopin Myriam , Locatelli Franco , Darbyshire Philippe , Handgretinger Rupert , Balduzzi Adriana , Owoc-Lempach Joanna , Fagioli Franca , Or Reuven , Peters Christina , Aversa Franco , Polge Emmanuelle , Dini Giorgio , Rocha Vanderson 
Published: December 2009

Abstract
T cell–depleted haploidentical hematopoietic stem cell transplantation (haploHSCT) is an option to treat children with very high-risk acute lymphoblastic leukemia (ALL) lacking an HLA-identical donor. We analyzed 127 children with ALL who underwent haploHSCT in first (n = 22), second (n = 48), or third (n = 32), complete remission or in relapse (n = 25). The 5-year leukemia-free survival (LFS) was 30%, 34%, 22%, and 0%, respectively. A risk-factor analysis was performed for patients who underwent transplantation in remission (n = 102). Five-year nonrelapse mortality (NRM), relapse incidence (RI), and LFS were 37%, 36%, and 27%, respectively. A trend of improved LFS rate and decreased RI was observed for children given a graft with higher number of CD34+ cells (adjusted P = .09 and P = .07, respectively). In a multivariate analysis, haploHSCT performed in larger centers (performing ≥ 231 allotransplantations in the studied period) was associated with improved LFS rate and decreased RI (adjusted P = .01 and P = .04, respectively), adjusting for different patient-, disease-, and transplant-related factors such as number of previous autotransplantations, cytomegalovirus serology status, type of T-cell depletion, and use of total body irradiation and antithymocyte globulin. In conclusion, higher CD34+ cell dose and better patient selection may improve outcomes of children with ALL who undergo a haploHSCT. Transplant centers initiating programs on haploHSCT for children may collaborate with more experienced centers.
Aberrant immunophenotype of blasts in myelodysplastic syndromes is a clinically relevant biomarker in predicting response to growth factor treatment
Authors: Westers Theresia M. , Alhan Canan , Chamuleau Martine E. D. , van der Vorst Maurice J. D. L. , Eeltink Corien , Ossenkoppele Gert J. , van de Loosdrecht Arjan A. 
Published: December 2009

Abstract
Myelodysplastic syndromes (MDS) are a group of clonal disorders of the bone marrow characterized by peripheral cytopenias. Standard treatment in low- and intermediate-I–risk MDS is supportive therapy consisting of regular transfusions and growth factors, that is, erythropoietin (Epo) and granulocyte-colony-stimulating factor (G-CSF). Because flow cytometric analysis of MDS bone marrow samples can identify clinically relevant subgroups regarding transfusion dependency and disease progression, we addressed the question whether flow cytometry (FCM) was instrumental in predicting response. In 46 patients with low- and intermediate-I–risk MDS that were treated with Epo/G-CSF, low Epo level and low transfusion need were associated with response to Epo/G-CSF. Interestingly, aberrant phenotype of myeloblasts identified nonresponders among patients with the greatest response probability according to the predictive model of Hellström-Lindberg et al. Moreover, aberrant FCM of myeloblasts acted as a significant biomarker for treatment failure in multivariate analysis. A new predictive model based on the basis FCM combined with previously validated Epo levels is proposed defining 3 subgroups with 94%, 17%, and 11% response probability. In conclusion, FCM may add significantly to well-known predictive parameters in selecting MDS patients eligible for Epo/G-CSF treatment. This is of relevance regarding prevention of treatment failure.
Molecular evolution of the pDo500 satellite DNA family in Dolichopoda cave crickets (Rhaphidophoridae)
Authors: Martinsen Lene , Venanzetti Federica , Johnsen Arild , Sbordoni Valerio , Bachmann Lutz 
Published: December 2009

AbstractBackgroundNon-coding satellite DNA (satDNA) usually has a high turn-over rate frequently leading to species specific patterns. However, some satDNA families evolve more slowly and can be found in several related species. Here, we analyzed the mode of evolution of thepDo500satDNA family ofDolichopodacave crickets. In addition, we discuss the potential of slowly evolving satDNAs as phylogenetic markers.ResultsWe sequenced 199 genomic or PCR amplified satDNA repeats of thepDo500family from 12Dolichopodaspecies. For the 38 populations under study, 39pDo500consensus sequences were deduced. Phylogenetic analyses using Bayesian, Maximum Parsimony, and Maximum Likelihood approaches yielded largely congruent tree topologies. The vast majority ofpDo500sequences grouped according to species designation. Scatter plots and statistical tests revealed a significant correlation between genetic distances for satDNA and mitochondrial DNA. Sliding window analyses showed species specific patterns of variable and conserved regions. The evolutionary rate of thepDo500satDNA was estimated to be 1.63-1.78% per lineage per million years.ConclusionsThepDo500satDNA evolves gradually at a rate that is only slightly faster than previously published rates of insect mitochondrial COI sequences. ThepDo500phylogeny was basically congruent with the previously published mtDNA phylogenies. Accordingly, the slowly evolvingpDo500satDNA family is indeed informative as a phylogenetic marker.
Identification and dynamics of a beneficial mutation in a long-term evolution experiment with Escherichia coli
Authors: Stanek Mark T , Cooper Tim F , Lenski Richard E 
Published: December 2009

AbstractBackgroundTwelve populations ofE. coliwere serially propagated for 20,000 generations in a glucose-supplemented minimal medium in order to study the dynamics of evolution. We sought to find and characterize one of the beneficial mutations responsible for the adaptation and other phenotypic changes, including increased cell size, in one of these populations.ResultsWe used transposon-tagging followed by P1-transduction into the ancestor, screening for increased cell size and fitness, co-transduction analysis, and DNA sequencing. We identified a 1-bp insertion in the BoxG1 region located upstream ofglmUS, an operon involved in cell-wall biosynthesis. When transduced into the ancestor, this mutation increased competitive fitness by about 5%. This mutation spread through its population of origin between 500 and 1500 generations. Mutations in this region were not found in the other 11 evolving populations, even after 20,000 generations.ConclusionThe 1-bp insertion in the BoxG1 region nearglmUSwas demonstrably beneficial in the environment in which it arose. The absence of similar mutations in the other evolved populations suggests that they substituted other mutations that rendered this particular mutation unimportant. These results show the unpredictability of adaptive evolution, whereas parallel substitutions at other loci in these same populations reveal the predictability.
Acute Myeloid Leukemia With Biallelic CEBPA Gene Mutations and Normal Karyotype Represents a Distinct Genetic Entity Associated With a Favorable Clinical Outcome
Authors: Dufour Annika , Schneider Friederike , Metzeler Klaus H. , Hoster Eva , Schneider Stephanie , Zellmeier Evelyn , Benthaus Tobias , Sauerland Maria-Cristina , Berdel Wolfgang E. , Büchner Thomas , Wörmann Bernhard , Braess Jan , Hiddemann Wolfgang , Bohlander Stefan K. , Spiekermann Karsten 
Published: December 2009

Purpose CEBPA mutations are found as either biallelic (biCEBPA) or monoallelic (moCEBPA). We set out to explore whether the kind of CEBPA mutation is of prognostic relevance in cytogenetically normal (CN) acute myeloid leukemia (AML). Patients and Methods Four hundred sixty-seven homogeneously treated patients with CN-AML were subdivided into moCEBPA, biCEBPA, and wild-type (wt) CEBPA patients. The subgroups were analyzed for clinical parameters and for additional mutations in the NPM1, FLT3, and MLL genes. Furthermore, we obtained gene expression profiles using oligonucleotide microarrays. Results Only patients with biCEBPA had an improved median overall survival when compared with patients with wtCEBPA (not reached v 20.4 months, respectively; P = .018), whereas patients with moCEBPA (20.9 months) and wtCEBPA had a similar outcome (P = .506). Multivariable analysis confirmed biCEBPA, but not moCEBPA, mutations as an independent favorable prognostic factor. Interestingly, biCEBPA mutations, compared with wtCEBPA, were never associated with mutated NPM1 (0% v 43%, respectively; P < .001) and rarely associated with FLT3 internal tandem duplication (ITD; 5% v 23%, respectively; P = .059), whereas patients with moCEBPA had a similar frequency of mutated NPM1 and a significantly higher association with FLT3-ITD compared with patients with wtCEBPA (44% v 23%, respectively; P = .037). Furthermore, patients with biCEBPA showed a homogeneous gene expression profile that was characterized by downregulation of HOX genes, whereas patients with moCEBPA showed greater heterogeneity in their gene expression profiles. Conclusion Biallelic disruption of the N and C terminus of CEBPA is required for the favorable clinical outcome of CEBPA-mutated patients and represents a distinct molecular subtype of CN-AML with a different frequency of associated gene mutations. These findings are of great significance for risk-adapted therapeutic strategies in AML.
Attempts to Optimize Induction and Consolidation Treatment in Acute Myeloid Leukemia: Results of the MRC AML12 Trial
Authors: Burnett Alan K. , Hills Robert K. , Milligan Donald W. , Goldstone Anthony H. , Prentice Archibald G. , McMullin Mary-Frances , Duncombe Andrew , Gibson Brenda , Wheatley Keith 
Published: December 2009

Purpose To optimize treatment for younger patients with acute myeloid leukemia and high-risk myelodysplastic syndrome by comparing induction options and the number of consolidation courses and whether consolidation should include transplantation. Patients and Methods We randomly assigned 1,658 patients younger than age 60 years to receive mitoxantrone/cytarabine/etoposide versus cytarabine/daunorubicin/etoposide and subsequently 1,193 patients to daunorubicin/cytarabine/thioguanine (DAT) where the cytarabine dose was standard (S-DAT) versus double the standard dose (H-DAT). Patients in this randomization were randomly assigned to all-trans-retinoic acid or not. In consolidation, 992 patients were randomly assigned between a total of four courses versus five courses, and 324 patients who were not good risk were randomly assigned to transplantation or chemotherapy as the final course. Results Complete remission (CR) was achieved in 74% of patients and CR without recovery was achieved in an additional 11%; overall survival (OS) at 8 years was 38%. No differences in CR, relapse-free survival, relapse, or OS were seen between any of the induction randomizations except for a reduction in relapse risk (RR) on the mitoxantrone arm, which was offset by increased myelosuppression and deaths in CR. The addition of a fifth course did not improve OS and may be detrimental in older patients. Although transplantation reduced RR, it did not improve OS for the intermediate-risk group but was probably of benefit in high-risk patients. Conclusion Several chemotherapy schedules achieved similar remission rates and OS. Four courses of chemotherapy are adequate, but the addition of transplantation as a final course does not improve OS. New agents are required to enhance conventional chemotherapy.
DNA Methylation Predicts Survival and Response to Therapy in Patients With Myelodysplastic Syndromes
Authors: Shen Lanlan , Kantarjian Hagop , Guo Yi , Lin E , Shan Jianqin , Huang Xuelin , Berry Donald , Ahmed Saira , Zhu Wei , Pierce Sherry , Kondo Yutaka , Oki Yasuhiro , Jelinek Jaroslav , Saba Hussain , Estey Eli , Issa Jean-Pierre J. 
Published: December 2009

Purpose The current classification systems of myelodysplastic syndromes (MDS), including the International Prognostic Scoring System (IPSS), do not fully reflect the molecular heterogeneity of the disease. Molecular characterization may predict clinical outcome and help stratify patients for targeted therapies. Epigenetic therapy using decitabine, a DNA hypomethylating agent, is clinically effective for the treatment of MDS. Therefore, we investigated the association between DNA methylation and clinical outcome in MDS. Patients and Methods We screened 24 patients with MDS for promoter CpG island methylation of 24 genes and identified aberrant hypermethylation at 10 genes. We then performed quantitative methylation analyses by bisulfite pyrosequencing of the identified genes in 317 patient samples from three independent studies and assessed relations between methylation and clinical outcome. Results In an initial training cohort of 89 patients with MDS, methylation frequencies of individual genes ranged from 7% to 70% and were highly concordant. Therefore, we defined a methylation z score based on all genes for each patient. We found that patients with higher levels of methylation, compared with patients with lower levels, had a shorter median overall survival (12.3 v 17.5 months, respectively; P = .04) and shorter median progression-free survival (6.4 v 14.9 months, respectively; P = .009). This methylation prognostic model was independent of age, sex, and IPSS group. Applied to two validation cohorts (228 patients), this model was confirmed as an independent prognostic predictor for survival. Although methylation at baseline did not correlate with clinical response to decitabine, we observed a significant correlation between reduced methylation over time and clinical responses. Conclusion DNA methylation predicts overall and progression-free survival in MDS.
Does Childhood Cancer Affect Parental Divorce Rates? A Population-Based Study
Authors: Syse Astri , Loge Jon H. , Lyngstad Torkild H. 
Published: December 2009

Purpose Cancer in children may profoundly affect parents' personal relationships in terms of psychological stress and an increased care burden. This could hypothetically elevate divorce rates. Few studies on divorce occurrence exist, so the effect of childhood cancers on parental divorce rates was explored. Patients and Methods Data on the entire Norwegian married population, age 17 to 69 years, with children age 0 to 20 years in 1974 to 2001 (N = 977,928 couples) were retrieved from the Cancer Registry, the Central Population Register, the Directorate of Taxes, and population censuses. Divorce rates for 4,590 couples who were parenting a child with cancer were compared with those of otherwise similar couples by discrete-time hazard regression models. Results Cancer in a child was not associated with an increased risk of parental divorce overall. An increased divorce rate was observed with Wilms tumor (odds ratio [OR], 1.52) but not with any of the other common childhood cancers. The child's age at diagnosis, time elapsed from diagnosis, and death from cancer did not influence divorce rates significantly. Increased divorce rates were observed for couples in whom the mothers had an education greater than high school level (OR, 1.16); the risk was particularly high shortly after diagnosis, for CNS cancers and Wilms tumors, for couples with children 0 to 9 years of age at diagnosis, and after a child's death. Conclusion This large, registry-based study shows that cancer in children is not associated with an increased parental divorce rate, except with Wilms tumors. Couples in whom the wife is highly educated appear to face increased divorce rates after a child's cancer, and this may warrant additional study.
Recipient Toll-like receptors contribute to chronic graft dysfunction by both MyD88- and TRIF-dependent signaling
Authors: Wang Shijun , Schmaderer Christoph , Kiss Eva , Schmidt Claudia , Bonrouhi Mahnaz , Porubsky Stefan , Gretz Norbert , Schaefer Liliana , Kirschning Carsten J. , Popovic Zoran V. , Gröne Hermann-Josef 
Published: December 2009

SUMMARYToll-like receptors (TLRs) recognize specific molecular patterns derived from microbial components (exogenous ligands) or stressed cells (endogenous ligands). Stimulation of these receptors leads to a pronounced inflammatory response in a variety of acute animal models. Chronic allograft dysfunction (CAD) was regarded as a candidate disease to test whether TLRs influence chronic fibrosing inflammation. Potential endogenous renal TLR ligands, specifically for TLR2 and TLR4, have now been detected by a significant upregulation of glucose regulated protein (GRP)-94, fibrinogen, heat shock protein (HSP)-60, HSP-70, biglycan (Bgn) and high-mobility group box chromosomal protein 1 (HMGB1) in the acute and chronic transplant setting. In a genetic approach to define the contribution of TLR2 and TLR4, and their adaptor proteins MyD88 and TRIF [Toll/interleukin (IL)-1 receptor domain-containing adaptor-protein inducing interferon β], to CAD, kidney transplantation of TLR wild-type grafts to recipients who were deficient in TLR2, TLR4, TLR2/4, MyD88 and TRIF was performed. TLR and adaptor protein deficiencies significantly improved the excretory function of chronic kidney grafts by between 65% and 290%, and histopathologic signs of chronic allograft damage were significantly ameliorated. T cells, dendritic cells (DCs) and foremost macrophages were reduced in grafts by up to 4.5-fold. The intragraft concentrations of IL-6, IL-10, monocyte chemotactic protein-1 (MCP-1) and IL-12p70 were significantly lower. TLR-, MyD88- and TRIF-deficient recipients showed a significant reduction in fibrosis. α-smooth muscle actin (α-SMA)-positive cells were decreased by up to ninefold, and collagen I and III were reduced by up to twofold. These findings highlight the functional relevance of TLRs and their two major signaling pathways in graft-infiltrating mononuclear cells in the pathophysiology of CAD. A TLR signaling blockade may be a therapeutic option for the prevention of CAD.