bluuebunny/crossref_metadata_2025_split huggingface dataset:
Economic sanctions, military activity, and road traffic crashes in Vojvodina, Serbia
Authors: Đurić P , Peek-Asa C 
Published: December 2008

Background:Political violence has not been examined as a risk factor for traumatic injuries from road traffic crashes.Objective:To identify trends in road traffic crashes related to war-related military activity and international economic sanctions in the Autonomous Province of Vojvodina, Serbia.Methods:Overall road traffic crashes and crashes leading to hospitalization and fatality in Vojvodina, Serbia were examined from 1996 through 2005. Rates were calculated per 100 000 population and per 10 000 registered vehicles. Three time periods were examined: years with international sanctions and military activity (1996–1999); years with international sanctions but no military activity (2000–2001); years with neither sanctions nor military activity (2002–2005).Results:Compared with the period with neither sanctions nor military activity, severe injury crashes were 1.23 times more common (95% CI 1.19 to 1.27) during the period with sanctions and military activity and 1.21 times more common (95% CI 1.16 to 1.27) during the period with sanctions but no military activity.Conclusions:The data suggest that vehicle travel became safer after the end of military action and economic sanctions. Road traffic safety needs to be a priority during both periods of political unrest and its recovery phase.
Plasma Insulin-like Growth Factors, Insulin-like Binding Protein-3, and Outcome in Metastatic Colorectal Cancer: Results from Intergroup Trial N9741
Authors: Fuchs Charles S. , Goldberg Richard M. , Sargent Daniel J. , Meyerhardt Jeffrey A. , Wolpin Brian M. , Green Erin M. , Pitot Henry C. , Pollak Michael 
Published: December 2008

Abstract
Purpose: Insulin-like growth factor (IGF)-I and IGF-II stimulate neoplastic cell growth and inhibit apoptosis, whereas IGF-binding protein-3 (IGFBP-3) inhibits the bioavailability of IGF-I and has independent proapoptotic activity. We examined the influence of baseline plasma levels of IGF-I, IGF-II, IGFBP-3, and C-peptide on outcome among patients receiving first-line chemotherapy for metastatic colorectal cancer.
Experimental Design: The plasma levels of IGF-I, IGF-II, IGFBP-3, and C-peptide as well as data on prognostic factors and body size were measured at baseline among 527 patients participating in a randomized trial of first-line chemotherapy for metastatic colorectal cancer.
Results: Higher baseline plasma IGFBP-3 levels were associated with a significantly greater chemotherapy response rate (P = 0.03) after adjusting for other prognostic factors, whereas neither IGF-I nor IGF-II levels significantly predicted tumor response. Higher levels of IGF-I, IGF-II, and IGFBP-3 were all univariately associated with improved overall survival (P = 0.0001 for all). In a model that mutually adjusted for IGF-I and IGFBP-3, as well as other prognostic factors, increasing baseline-circulating IGFBP-3 was associated with a significantly longer time to tumor progression (P = 0.03), whereas circulating IGF-I was not associated with disease progression (P = 0.95). Levels of C-peptide were not associated with any measure of patient outcome.
Conclusion: Among colorectal cancer patients receiving first-line chemotherapy, increasing levels of IGFBP-3, an endogenous antagonist to IGF-I, are associated with an improved objective treatment response and a prolonged time to cancer progression. The IGF pathway may represent an important target for future treatment strategies.
Mesoscale Convective Systems and Critical Clusters
Authors: Peters Ole , Neelin J. David , Nesbitt Stephen W. 
Published: December 2008

AbstractSize distributions and other geometric properties of mesoscale convective systems (MCSs), identified as clusters of adjacent pixels exceeding a precipitation threshold in satellite radar images, are examined with respect to a recently identified critical range of water vapor. Satellite microwave estimates of column water vapor and precipitation show that the onset of convection and precipitation in the tropics can be described as a phase transition, where the rain rate and likelihood of rainfall suddenly increase as a function of water vapor. This is confirmed in Tropical Rainfall Measuring Mission radar data used here. Percolation theory suggests that cluster properties should be highly sensitive to changes in the density of occupied pixels, which here translates into a rainfall probability, which in turn sensitively depends on the water vapor. To confirm this, clusters are categorized by their prevalent water vapor. As expected, mean cluster size and radius of gyration strongly increase as the critical water vapor is approached from below. In the critical region one finds scale-free size distributions spanning several orders of magnitude. Large clusters are typically from the critical region: at low water vapor most clusters are small, and supercritical water vapor values are too rare to contribute much. The perimeter of the clusters confirms previous observations in satellite, field, and model data of robust nontrivial scaling. The well-known area–perimeter scaling is fully compatible with the quantitative prediction from the plausible null model of gradient percolation, where the accessible hull is a fractal object with dimension 4/3.
Projected Midlatitude Continental Summer Drying: North America versus Europe
Authors: Rowell David P. 
Published: December 2008

Abstract
A common signal in climate model projections is a decline in average summer rainfall over midlatitude continents due to anthropogenic warming. Most models suggest this rainfall decline will be less severe over North America than over Europe. This study aims to understand this difference in continental response and make inferences about its reliability. Data are primarily derived from a “perturbed physics” ensemble of models [Quantifying Uncertainty in Model Predictions project, subensemble S4 (QUMP-S4)] and are also compared with data from a multimodel ensemble [the Coupled Model Intercomparison Project phase 3 (CMIP3)]. A description of the uncertainty of predicted summer rainfall decline over both continents and its broad similarity between the two ensembles suggests the possibility that the QUMP-S4 ensemble may include many of the mechanisms that cause the differential continental response in the CMIP3 ensemble. Analysis of the QUMP-S4 mechanisms and their variability across the ensemble lead to the following conclusions. Over western North America, it is judged that the change in summer rainfall is more uncertain than models suggest, with a decline that could be either more or less severe than that over Europe. This is due to the western North American region’s dependence on uncertain modeling of high-elevation winter–spring surface hydrology. Over eastern North America, it seems likely that summer rainfall will decline. In particular, this decline is likely to be less severe than that over continental Europe since this difference primarily depends on reliable aspects of the models. However, a further, but speculative, conclusion is that these mechanisms could also lead to a larger increase in extreme rainfall events over eastern North America than over Europe.
Response to a Steady Poleward Outflow. Part I: The Linear, Quasigeostrophic Problem
Authors: Durland Theodore S. , Pedlosky Joseph , Spall Michael A. 
Published: December 2008

Abstract
The response of a zonal channel to a uniform, switched-on but subsequently steady poleward outflow is presented. An eastward coastal current with a Kelvin wave’s cross-shore structure is found to be generated instantly upon initiation of the outflow. The current is essentially in geostrophic balance everywhere except for the vicinity of the outflow channel mouth, where the streamlines must cross planetary vorticity contours to feed the current. The adjustment of this region generates a plume that propagates westward at Rossby wave speeds. The cross-shore structure of the plume varies with longitude, and at any given longitude it evolves with time. The authors show that the plume evolution can be understood both conceptually and quantitatively as the westward propagation of the Kelvin current’s meridional spectrum, with each spectral element propagating at its own Rossby wave group velocity.
Association of ACE I/D Gene Polymorphism With Vascular Dementia: A Meta-Analysis
Authors: Hua Liu  , Ming Liu  , Wei Li  , Bo Wu  , Zhang Shi-hong , Yuan Fang  , Yi Wang  
Published: December 2008

Background: Vascular dementia is the second common cause of dementia, only second to Alzheimer's disease in later life, and has a greater mortality risk than Alzheimer's disease among the elderly population group. The angiotensin-converting enzyme insertion/deletion polymorphism as a risk factor in vascular dementia has been suggested, but direct evidence from genetic association studies remain inconclusive. We performed a meta-analysis pooling data from all relevant studies in order to determine the effect of the insertion/deletion polymorphism on the vascular dementia. Methods: We applied a random-effects model or fixed-effects model to combine odds ratio and 95% confidence intervals. Q statistic was used to evaluate the homogeneity, and Egger's test and Funnel plot were used to assess publication bias. Results: A total of 10 studies were included worldwide. Publication bias was not observed. There was no evidence of the association of angiotensin-converting enzyme insertion/deletion polymorphism with the vascular dementia in general or in the Asian populations or in the Caucasian populations. Conclusions: The angiotensin-converting enzyme insertion/deletion polymorphism might be neutral to vascular dementia.
Association of programmed cell death 1 polymorphisms and systemic lupus erythematosus: a meta-analysis
Authors: Lee YH , Woo JH , Choi SJ , Ji JD , Song GG 
Published: December 2008

Programmed cell death 1 ( PDCD1 or PD1) polymorphisms have been inconsistently reported to be associated with systemic lupus erythematosus (SLE). The aim of this study was to explore whether the PDCD1 polymorphisms confer a susceptibility to SLE and lupus nephritis (LN). We conducted a meta-analysis on the association of PDCD1 polymorphisms with SLE in overall and specific ethnic populations. A total of 15 separate comparisons were included in this meta-analysis consisting of nine Europeans, two Latin Americans, two Africans, one Asian and one unknown participant. In subgroup analysis, the PD1.3A allele was significantly associated with SLE in Latin Americans (OR = 3.073, 95% CI = 1.416–6.461, P = 0.003), but not in patients of European and African decent. The PD1.3A allele was a risk factor for LN in European descendants (OR = 2.207, 95% CI = 1.488–3.467, P < 0.001). The PD1.5C allele was a risk factor for SLE in Europeans (OR = 1.297, 95% CI = 1.024–1.643, P = 0.031). In conclusion, this meta-analysis demonstrated an association of the PD1.3A allele with LN in European and SLE in Latin-American populations. Furthermore, the PD1.5C allele was associated with SLE susceptibility in Europeans.
Thrombotic thrombocytopenic purpura in systemic lupus erythematosus: risk factors and clinical outcome: a single centre study
Authors: Kwok SK , Ju JH , Cho CS , Kim HY , Park SH 
Published: December 2008

The study was undertaken to investigate clinical characteristics of thrombotic thrombocytopenic purpura (TTP) in patients with SLE and to determine risk factors and clinical outcome of TTP in patients with SLE. Among the 1203 patients with SLE admitted to catholic medical centre of the catholic university of Korea from January 1990 to December 2006, 26 patients with SLE were found to admit with TTP. TTP was defined if microangiopathic haemolytic anaemia, thrombocytopenia and negative Coombs’ test were present and when at least one of the following signs was noted: renal impairment, neurologic deficit or fever. Eighty-seven patients with SLE who admitted with other manifestations, matched for age and sex, were included as disease controls. Data were retrospectively analysed based on medical records. There were no significant demographic characteristics between SLE patients with TTP and those with other manifestations. Multivariate analysis showed that independent risk factors for the development of TTP included high SLE disease activity index score (SLEDAI > 10, P = 0.006) and coexisting nephritis ( P = 0.004). Among the 26 SLE patients with TTP, 12 died during admission period (in-hospital mortality rate: 46.1%). SLE patients with infection or neurologic manifestations had higher mortality rates. Multivariate analysis showed that infection is the only independent risk factor for mortality in SLE patients with TTP ( P = 0.035). Patients with SLE who are in the active stage or who have renal involvement have the increased risk for TTP. Development of TTP in patients with SLE can be fatal. Therefore, intensive therapy will be needed especially in the presence of infection.
Effects of rituximab on resistant SLE disease including lung involvement
Authors: Reynolds JA , Toescu V , Yee CS , Prabu A , Situnayake D , Gordon C 
Published: December 2008

We present a retrospective review of 11 patients with refractory systemic lupus erythematosus (SLE) treated with rituximab after failing corticosteroids and at least one other immunosuppressive drug. We measured clinical response using the Classic British Isles Lupus Assessment Group (BILAG) index, serum complement and reduction in maintenance prednisolone dose. B cells were measured using flow cytometry, and lung function testing was used to assess severe pulmonary disease (three patients). The median patient age was 42 years (range, 25–64) with median disease duration 6 years (range, 2–12). In all, 10 of 11 patients responded initially, with median global BILAG reduction of 7.5 at 6 months ( P = 0.007), with loss of all A and B scores by 7 months. Rituximab treatment was associated with normalisation of complement (C3 P = 0.008, C4 P = 0.018) and reduction in steroid requirement, median reduction 15 mg/day ( P = 0.036). In 9 of 10 patients who responded, all other immunosuppressants were stopped. There was no significant difference in anti-dsDNA antibody titres in these responders, but they were negative or had low titres at baseline. B-cell depletion continued for median 4 months (range, 2–9), and disease flare occurred at a median 6.6 months (range, 1.5–23) and was preceded by B-cell recovery in all but two patients. Rituximab was beneficial in refractory SLE including severe neurological and cardiorespiratory disease by inducing disease remission, allowing withdrawal of other agents and reduction in steroid requirement. Rituximab appeared to stabilise and possibly improve progressive lung disease.
Acute Myeloid Leukemia: The Challenge of Capturing Disease Variety
Authors: Löwenberg Bob 
Published: December 2008

AbstractThe difference between success and failure of treatment of acute myeloid leukemia (AML) is largely determined by genotypic leukemia-specific differences among patients. The diversity of AML genotypes result from somatic genetic alterations settling down in succession in an individual’s leukemia clone during the development of the disease. Gene mutations, gene expression abnormalities and other molecular alterations (e.g., microRNA variations) affect critical functions in AML cells, and may exert profound effects on the therapeutic response and outcome of the disease. Prototypes of common clinically significant gene aberrations involve transcription factors, signaling molecules and growth factor receptors. The expanding knowledge in this area allowing for risk stratified therapy decisions and the development of targeted drug therapy, is becoming an increasingly important part of the modern individualized clinical management of AML. This chapter highlights recent insights into the diagnostic, prognostic and therapeutic impact of chromosomal (e.g., the so-called monosomal karyotype) as well as particular genomic abnormalities, and presents examples of decision algorithms for individualized therapy.
Recognizing and Managing Chronic Graft-Versus-Host Disease
Authors: Lee Stephanie J. , Flowers Mary E. D. 
Published: December 2008

Abstract
Chronic graft-versus-host disease (GVHD) is an immune-mediated disorder that occurs frequently after allogeneic hematopoietic cell transplantation (HCT). Most cases are diagnosed within the first year at a median of 4 to 6 months after HCT, but 5–10% of cases are initially diagnosed beyond the first post-transplant year. Chronic GVHD most often involves the skin and mouth, but almost any other organ system can be involved. Correct diagnosis is critical so that appropriate therapy can be started promptly to minimize symptoms and prevent irreversible organ damage. Initial treatment should be with cortico-steroid-based therapy. Optimal secondary treatment as not been established, although a large number of agents may provide benefits. A 2004 NIH conference focused on development of consensus criteria for chronic GVHD. Six papers published in 2005 and 2006 propose consensus definitions for chronic GVHD diagnosis and scoring, pathology, biomarkers, response criteria, supportive care and design of clinical trials.
This review will focus on common clinical presentations and principles for managing chronic GVHD. The most frequently used secondary therapies and ongoing trials are summarized. New concepts from the NIH consensus conference are discussed.
Old and New Cancers after Hematopoietic-Cell Transplantation
Authors: Majhail Navneet S. 
Published: December 2008

Abstract
Relapse of primary disease and occurrence of new cancers can cause significant morbidity and mortality in recipients of autologous and allogeneic hematopoietic-cell transplantation (HCT). Treatment options for relapse are generally limited and can include disease-specific chemotherapy or targeted therapy. Additional relapse-directed therapies that are available for allogeneic HCT recipients include withdrawal of immunosuppression and donor lymphocyte infusion. Selected patients can be offered a second transplant procedure. Newer strategies to eliminate minimal residual disease and, in allogeneic HCT recipients, to augment the graft-versus-tumor effect are needed for patients who are at high risk for relapse after HCT. Second cancers after HCT include post-transplant lymphoproliferative disorder, hematologic malignancies and new solid cancers. The incidence of second solid cancers continues to rise without a plateau with increasing follow up of HCT survivors. Secondary myelodysplastic syndrome and acute leukemia are almost exclusively seen in autologous HCT recipients while post-transplant lymphoproliferative disorders complicate recipients of allogeneic HCT. Appropriate screening evaluations should be performed in HCT survivors to facilitate early detection and treatment of second cancers.
Mechanisms of Vasculopathy in Sickle Cell Disease and Thalassemia
Authors: Morris Claudia R. 
Published: December 2008

AbstractMany mechanisms contribute to the complex pathophysiology of sickle cell disease (SCD), with dysfunction of the vascular endothelium as a unifying theme. Specifically, hemolysis-associated low arginine and nitric oxide (NO) bioavailability, amplified by NO synthase uncoupling, elevated arginase activity, superoxide production, oxidative stress, accumulation of arginine analogs such as asymmetric dimethylarginine, ischemia-reperfusion injury, inflammation, apolipoprotein A-1 depletion, and a hypercoagulable state are significant mechanisms contributing to endothelial dysfunction. Genetic polymorphisms also influence disease severity. Clearly the variable spectrum of disease is the consequence of multiple events and genetic susceptibility that go beyond the occurrence of a single amino acid substitution in the beta globin chain of hemoglobin. Recent studies begin to demonstrate overlap among these seemingly unrelated processes. Impaired NO bioavailability represents the central feature of endothelial dysfunction, and is a common denominator in the pathogenesis of vasculopathy in SCD. The consequences of decreased NO bioavailability include endothelial cell activation, upregulation of the potent vasoconstrictor endothelin-1, vasoconstriction, platelet activation, increased tissue factor, and activation of coagulation, all of which ultimately translate into the clinical manifestations of SCD. Evidence supporting vasculopathy subphenotypes in SCD, including pulmonary hypertension, priapism, cutaneous leg ulceration, and stroke, will be reviewed and relevance to other hemolytic disorders including the thalassemia syndromes will be considered.
New Strategies for the Optimal Use of Platelet Transfusions
Authors: Blajchman Morris A. , Slichter Sherrill J. , Heddle Nancy M. , Murphy Michael F. 
Published: December 2008

Abstract
Patients with severe thrombocytopenia are presumed to be at increased risk for bleeding, and consequently it has been standard practice for the past four decades to give allogeneic platelet transfusions to severely thrombocytopenic patients as supportive care. Platelet transfusions may be given either prophylactically to reduce the risk of bleeding, in the absence of clinical hemorrhage (prophylactic transfusions), or to control active bleeding when present (therapeutic transfusions). While no one would argue with the need for platelet transfusions in the face of severe bleeding, important questions remain about what constitutes clinically significant bleeding and whether a strategy of prophylactic platelet transfusions is effective in reducing the risk of bleeding in clinically stable patients. It is now uncommon for patients undergoing intensive chemotherapy or bone marrow transplantation to die of hemorrhage, but it is open to debate as to what degree platelet transfusions have been responsible for this change in outcome, given the many other advances in other aspects of supportive care.
If a prophylactic strategy is followed, the optimal transfusion trigger or quantity of platelets to be transfused prophylactically per transfusion episode needs to be addressed in adequately powered clinical trials, but these remain highly controversial issues. This is because, until recently, there have been few high-quality, prospective, randomized clinical trial (RCT) data for evaluating the relative effects of different platelet transfusion regimens or platelet doses on clinical outcomes. Moreover, most of these RCTs have not used bleeding as the primary outcome measure. Two such studies on platelet dose have now been undertaken, the PLADO (Prophylactic PLAtelet DOse) and the SToP (Strategies for the Transfusion of Platelets) trials. Data from these RCTs are not contained in this overview, as these data have not yet been completely analyzed or submitted for peer review publication.
In addition to the above, several recent observational studies have raised the possibility that there is not a clear association between the occurrence of a major clinical bleeding episode and the platelet count in thrombocytopenic patients. Such findings have led to the questioning of the efficacy of prophylactic platelet transfusions in all clinically stable patients, and whether a policy of therapeutic transfusions used only when patients have clinical bleeding might be as effective and safe for selected patients. At least two RCTs evaluating the relative value of prophylactic versus therapeutic platelet transfusions have been initiated in thrombocytopenic patients with hematological malignancies. One such study, known as the TOPPS (Trial of Prophylactic Platelets Study) study, is currently underway in the U.K.