scispace - formally typeset
Search or ask a question

Showing papers by "University of Washington published in 2005"


Journal ArticleDOI
TL;DR: The authors delineate analytic procedures specific to each approach and techniques addressing trustworthiness with hypothetical examples drawn from the area of end-of-life care.
Abstract: Content analysis is a widely used qualitative research technique. Rather than being a single method, current applications of content analysis show three distinct approaches: conventional, directed, or summative. All three approaches are used to interpret meaning from the content of text data and, hence, adhere to the naturalistic paradigm. The major differences among the approaches are coding schemes, origins of codes, and threats to trustworthiness. In conventional content analysis, coding categories are derived directly from the text data. With a directed approach, analysis starts with a theory or relevant research findings as guidance for initial codes. A summative content analysis involves counting and comparisons, usually of keywords or content, followed by the interpretation of the underlying context. The authors delineate analytic procedures specific to each approach and techniques addressing trustworthiness with hypothetical examples drawn from the area of end-of-life care.

31,398 citations


Journal ArticleDOI
TL;DR: In patients with NYHA class II or III CHF and LVEF of 35 percent or less, amiodarone has no favorable effect on survival, whereas single-lead, shock-only ICD therapy reduces overall mortality by 23 percent.
Abstract: background Sudden death from cardiac causes remains a leading cause of death among patients with congestive heart failure (CHF). Treatment with amiodarone or an implantable cardioverter–defibrillator (ICD) has been proposed to improve the prognosis in such patients. methods We randomly assigned 2521 patients with New York Heart Association (NYHA) class II or III CHF and a left ventricular ejection fraction (LVEF) of 35 percent or less to conventional therapy for CHF plus placebo (847 patients), conventional therapy plus amiodarone (845 patients), or conventional therapy plus a conservatively programmed, shockonly, single-lead ICD (829 patients). Placebo and amiodarone were administered in a double-blind fashion. The primary end point was death from any cause. results The median LVEF in patients was 25 percent; 70 percent were in NYHA class II, and 30 percent were in class III CHF. The cause of CHF was ischemic in 52 percent and nonischemic in 48 percent. The median follow-up was 45.5 months. There were 244 deaths (29 percent) in the placebo group, 240 (28 percent) in the amiodarone group, and 182 (22 percent) in the ICD group. As compared with placebo, amiodarone was associated with a similar risk of death (hazard ratio, 1.06; 97.5 percent confidence interval, 0.86 to 1.30; P=0.53) and ICD therapy was associated with a decreased risk of death of 23 percent (0.77; 97.5 percent confidence interval, 0.62 to 0.96; P=0.007) and an absolute decrease in mortality of 7.2 percentage points after five years in the overall population. Results did not vary according to either ischemic or nonischemic causes of CHF, but they did vary according to the NYHA class. conclusions In patients with NYHA class II or III CHF and LVEF of 35 percent or less, amiodarone has no favorable effect on survival, whereas single-lead, shock-only ICD therapy reduces overall mortality by 23 percent.

5,903 citations


Journal ArticleDOI
John W. Belmont1, Andrew Boudreau, Suzanne M. Leal1, Paul Hardenbol  +229 moreInstitutions (40)
27 Oct 2005
TL;DR: A public database of common variation in the human genome: more than one million single nucleotide polymorphisms for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted.
Abstract: Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.

5,479 citations


Journal ArticleDOI
TL;DR: In this paper, a large-scale correlation function measured from a spectroscopic sample of 46,748 luminous red galaxies from the Sloan Digital Sky Survey is presented, which demonstrates the linear growth of structure by gravitational instability between z ≈ 1000 and the present and confirms a firm prediction of the standard cosmological theory.
Abstract: We present the large-scale correlation function measured from a spectroscopic sample of 46,748 luminous red galaxies from the Sloan Digital Sky Survey. The survey region covers 0.72h −3 Gpc 3 over 3816 square degrees and 0.16 < z < 0.47, making it the best sample yet for the study of large-scale structure. We find a well-detected peak in the correlation function at 100h −1 Mpc separation that is an excellent match to the predicted shape and location of the imprint of the recombination-epoch acoustic oscillations on the low-redshift clustering of matter. This detection demonstrates the linear growth of structure by gravitational instability between z ≈ 1000 and the present and confirms a firm prediction of the standard cosmological theory. The acoustic peak provides a standard ruler by which we can measure the ratio of the distances to z = 0.35 and z = 1089 to 4% fractional accuracy and the absolute distance to z = 0.35 to 5% accuracy. From the overall shape of the correlation function, we measure the matter density mh 2 to 8% and find agreement with the value from cosmic microwave background (CMB) anisotropies. Independent of the constraints provided by the CMB acoustic scale, we find m = 0.273 ±0.025+0.123(1+ w0)+0.137K. Including the CMB acoustic scale, we find that the spatial curvature is K = −0.010 ± 0.009 if the dark energy is a cosmological constant. More generally, our results provide a measurement of cosmological distance, and hence an argument for dark energy, based on a geometric method with the same simple physics as the microwave background anisotropies. The standard cosmological model convincingly passes these new and robust tests of its fundamental properties. Subject headings: cosmology: observations — large-scale structure of the universe — distance scale — cosmological parameters — cosmic microwave background — galaxies: elliptical and lenticular, cD

4,428 citations


Journal ArticleDOI
TL;DR: This paper found that the majority of managers would avoid initiating a positive NPV project if it meant falling short of the current quarter's consensus earnings, and more than three-fourths of the surveyed executives would give up economic value in exchange for smooth earnings.

4,341 citations


Journal ArticleDOI
TL;DR: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them as mentioned in this paper.
Abstract: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in ∼50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

4,258 citations


Journal ArticleDOI
TL;DR: In vivo, antibody to IL- 17 inhibited chemokine expression in the brain during experimental autoimmune encephalomyelitis, whereas overexpression of IL-17 in lung epithelium caused Chemokine production and leukocyte infiltration, indicating a unique T helper lineage that regulates tissue inflammation.
Abstract: Interleukin 17 (IL-17) has been linked to autoimmune diseases, although its regulation and function have remained unclear. Here we have evaluated in vitro and in vivo the requirements for the differentiation of naive CD4 T cells into effector T helper cells that produce IL-17. This process required the costimulatory molecules CD28 and ICOS but was independent of the cytokines and transcription factors required for T helper type 1 or type 2 differentiation. Furthermore, both IL-4 and interferon-γ negatively regulated T helper cell production of IL-17 in the effector phase. In vivo, antibody to IL-17 inhibited chemokine expression in the brain during experimental autoimmune encephalomyelitis, whereas overexpression of IL-17 in lung epithelium caused chemokine production and leukocyte infiltration. Thus, IL-17 expression characterizes a unique T helper lineage that regulates tissue inflammation.

4,196 citations


Journal ArticleDOI
17 Nov 2005-Nature
TL;DR: In a warmer world, less winter precipitation falls as snow and the melting of winter snow occurs earlier in spring, which leads to a shift in peak river runoff to winter and early spring, away from summer and autumn when demand is highest.
Abstract: All currently available climate models predict a near-surface warming trend under the influence of rising levels of greenhouse gases in the atmosphere. In addition to the direct effects on climate--for example, on the frequency of heatwaves--this increase in surface temperatures has important consequences for the hydrological cycle, particularly in regions where water supply is currently dominated by melting snow or ice. In a warmer world, less winter precipitation falls as snow and the melting of winter snow occurs earlier in spring. Even without any changes in precipitation intensity, both of these effects lead to a shift in peak river runoff to winter and early spring, away from summer and autumn when demand is highest. Where storage capacities are not sufficient, much of the winter runoff will immediately be lost to the oceans. With more than one-sixth of the Earth's population relying on glaciers and seasonal snow packs for their water supply, the consequences of these hydrological changes for future water availability--predicted with high confidence and already diagnosed in some regions--are likely to be severe.

3,831 citations


Journal ArticleDOI
TL;DR: It is estimated that each year in the United States there are 190,600 cases of acute lung injury, which are associated with 74,500 deaths and 3.6 million hospital days, considerably higher than previous reports have suggested.
Abstract: BACKGROUND Acute lung injury is a critical illness syndrome consisting of acute hypoxemic respiratory failure with bilateral pulmonary infiltrates that are not attributed to left atrial hypertension. Despite recent advances in our understanding of the mechanism and treatment of acute lung injury, its incidence and outcomes in the United States have been unclear. METHODS We conducted a prospective, population-based, cohort study in 21 hospitals in and around King County, Washington, from April 1999 through July 2000, using a validated screening protocol to identify patients who met the consensus criteria for acute lung injury. RESULTS A total of 1113 King County residents undergoing mechanical ventilation met the criteria for acute lung injury and were 15 years of age or older. On the basis of this figure, the crude incidence of acute lung injury was 78.9 per 100,000 person-years and the age-adjusted incidence was 86.2 per 100,000 person-years. The in-hospital mortality rate was 38.5 percent. The incidence of acute lung injury increased with age from 16 per 100,000 person-years for those 15 through 19 years of age to 306 per 100,000 person-years for those 75 through 84 years of age. Mortality increased with age from 24 percent for patients 15 through 19 years of age to 60 percent for patients 85 years of age or older (P<0.001). We estimate that each year in the United States there are 190,600 cases of acute lung injury, which are associated with 74,500 deaths and 3.6 million hospital days. CONCLUSIONS Acute lung injury has a substantial impact on public health, with an incidence in the United States that is considerably higher than previous reports have suggested.

3,358 citations


Book
01 Jan 2005
TL;DR: Haug, Sorensen, Gruber, Song, Relapse Prevention for Opioid Dependence, and Wheeler, George, Stoner, Enhancing the Relapse prevention model for Sex Offenders: Adding Recidivism Risk Reduction Therapy to Target Offenders' Dynamic Risk Needs.
Abstract: Marlatt, Witkiewitz, Relapse Prevention for Alcohol and Drug Problems. Blume, de la Cruz, Relapse Prevention among Diverse Populations. Kadden, Cooney, Treating Alcohol Problems. Shiffman, Kassel, Gwaltney, McChargue, Relapse Prevention for Smoking. Carroll, Rawson, Relapse Prevention for Stimulant Dependence. Haug, Sorensen, Gruber, Song, Relapse Prevention for Opioid Dependence. Roffman, Stephens, Relapse Prevention for Cannabis Abuse and Dependence. Kilmer, Cronce, Palmer, Relapse Prevention for Abuse of Club Drugs, Hallucinogens, Inhalants, and Steroids. Collins, Relapse Prevention for Eating Disorders and Obesity. Shaffer, LaPlante, Treatment of Gambling Disorders. Wheeler, George, Stoner, Enhancing the Relapse Prevention Model for Sex Offenders: Adding Recidivism Risk Reduction Therapy to Target Offenders' Dynamic Risk Needs. Zawacki, Stoner, George, Relapse Prevention for Sexually Risky Behaviors.

2,866 citations


Journal ArticleDOI
Joseph Adams1, Madan M. Aggarwal2, Zubayer Ahammed3, J. Amonett4  +363 moreInstitutions (46)
TL;DR: In this paper, the most important experimental results from the first three years of nucleus-nucleus collision studies at RHIC were reviewed, with emphasis on results of the STAR experiment.

Journal ArticleDOI
TL;DR: It is provided evidence that this value of shear viscosity to volume density of entropy may serve as a lower bound for a wide class of systems, thus suggesting that black hole horizons are dual to the most ideal fluids.
Abstract: The ratio of shear viscosity to volume density of entropy can be used to characterize how close a given fluid is to being perfect. Using string theory methods, we show that this ratio is equal to a universal value of [h-bar]/4pikB for a large class of strongly interacting quantum field theories whose dual description involves black holes in anti–de Sitter space. We provide evidence that this value may serve as a lower bound for a wide class of systems, thus suggesting that black hole horizons are dual to the most ideal fluids.

Journal ArticleDOI
TL;DR: In this paper, the authors present longitudinal measures of five-year change in the regional brain volumes in healthy adults and assess the average and individual differences in volume changes and the effects of age, sex and hypertension with latent difference score modeling.
Abstract: Brain aging research relies mostly on cross-sectional studies, which infer true changes from age differences. We present longitudinal measures of five-year change in the regional brain volumes in healthy adults. Average and individual differences in volume changes and the effects of age, sex and hypertension were assessed with latent difference score modeling. The caudate, the cerebellum, the hippocampus and the association cortices shrunk substantially. There was minimal change in the entorhinal and none in the primary visual cortex. Longitudinal measures of shrinkage exceeded cross-sectional estimates. All regions except the inferior parietal lobule showed individual differences in change. Shrinkage of the cerebellum decreased from young to middle adulthood, and increased from middle adulthood to old age. Shrinkage of the hippocampus, the entorhinal cortices, the inferior temporal cortex and the prefrontal white matter increased with age. Moreover, shrinkage in the hippocampus and the cerebellum accelerated with age. In the hippocampus, both linear and quadratic trends in incremental age-related shrinkage were limited to the hypertensive participants. Individual differences in shrinkage correlated across some regions, suggesting common causes. No sex differences in age trends except for the caudate were observed. We found no evidence of neuroprotective effects of larger brain size or educational attainment.

Journal ArticleDOI
22 Sep 2005-Nature
TL;DR: The isolation of a marine crenarchaeote that grows chemolithoautotrophically by aerobically oxidizing ammonia to nitrite—the first observation of nitrification in the Archaea is reported, suggesting that nitrifying marine Cren archaeota may be important to global carbon and nitrogen cycles.
Abstract: For years, microbiologists characterized the Archaea as obligate extremophiles that thrive in environments too harsh for other organisms. The limited physiological diversity among cultivated Archaea suggested that these organisms were metabolically constrained to a few environmental niches. For instance, all Crenarchaeota that are currently cultivated are sulphur-metabolizing thermophiles. However, landmark studies using cultivation-independent methods uncovered vast numbers of Crenarchaeota in cold oxic ocean waters. Subsequent molecular surveys demonstrated the ubiquity of these low-temperature Crenarchaeota in aquatic and terrestrial environments. The numerical dominance of marine Crenarchaeota--estimated at 10(28) cells in the world's oceans--suggests that they have a major role in global biogeochemical cycles. Indeed, isotopic analyses of marine crenarchaeal lipids suggest that these planktonic Archaea fix inorganic carbon. Here we report the isolation of a marine crenarchaeote that grows chemolithoautotrophically by aerobically oxidizing ammonia to nitrite--the first observation of nitrification in the Archaea. The autotrophic metabolism of this isolate, and its close phylogenetic relationship to environmental marine crenarchaeal sequences, suggests that nitrifying marine Crenarchaeota may be important to global carbon and nitrogen cycles.

Journal ArticleDOI
12 Jan 2005-JAMA
TL;DR: Substantial evidence supports screening all patients with diabetes to identify those at risk for foot ulceration and recommending certain prophylactic interventions, including patient education, prescription footwear, intensive podiatric care, and evaluation for surgical interventions.
Abstract: ContextAmong persons diagnosed as having diabetes mellitus, the prevalence of foot ulcers is 4% to 10%, the annual population-based incidence is 1.0% to 4.1%, and the lifetime incidence may be as high as 25%. These ulcers frequently become infected, cause great morbidity, engender considerable financial costs, and are the usual first step to lower extremity amputation.ObjectiveTo systematically review the evidence on the efficacy of methods advocated for preventing diabetic foot ulcers in the primary care setting.Data Sources, Study Selection, and Data ExtractionThe EBSCO, MEDLINE, and the National Guideline Clearinghouse databases were searched for articles published between January 1980 and April 2004 using database-specific keywords. Bibliographies of retrieved articles were also searched, along with the Cochrane Library and relevant Web sites. We reviewed the retrieved literature for pertinent information, paying particular attention to prospective cohort studies and randomized clinical trials.Data SynthesisPrevention of diabetic foot ulcers begins with screening for loss of protective sensation, which is best accomplished in the primary care setting with a brief history and the Semmes-Weinstein monofilament. Specialist clinics may quantify neuropathy with biothesiometry, measure plantar foot pressure, and assess lower extremity vascular status with Doppler ultrasound and ankle-brachial blood pressure indices. These measurements, in conjunction with other findings from the history and physical examination, enable clinicians to stratify patients based on risk and to determine the type of intervention. Educating patients about proper foot care and periodic foot examinations are effective interventions to prevent ulceration. Other possibly effective clinical interventions include optimizing glycemic control, smoking cessation, intensive podiatric care, debridement of calluses, and certain types of prophylactic foot surgery. The value of various types of prescription footwear for ulcer prevention is not clear.ConclusionsSubstantial evidence supports screening all patients with diabetes to identify those at risk for foot ulceration. These patients might benefit from certain prophylactic interventions, including patient education, prescription footwear, intensive podiatric care, and evaluation for surgical interventions.


Journal ArticleDOI
TL;DR: With the growing understanding of polymer gene-delivery mechanisms and continued efforts of creative polymer chemists, it is likely that polymer-based gene-Delivery systems will become an important tool for human gene therapy.
Abstract: The lack of safe and efficient gene-delivery methods is a limiting obstacle to human gene therapy. Synthetic gene-delivery agents, although safer than recombinant viruses, generally do not possess the required efficacy. In recent years, a variety of effective polymers have been designed specifically for gene delivery, and much has been learned about their structure–function relationships. With the growing understanding of polymer gene-delivery mechanisms and continued efforts of creative polymer chemists, it is likely that polymer-based gene-delivery systems will become an important tool for human gene therapy.

Journal ArticleDOI
01 Mar 2005-Immunity
TL;DR: Analysis of Foxp3 expression during thymic development suggests that this mechanism is not hard-wired but is dependent on TCR/MHC ligand interactions, and it is shown that expression ofFoxp3 is highly restricted to the subset alphabeta of T cells and, irrespective of CD25 expression, correlates with suppressor activity.

Journal ArticleDOI
TL;DR: The International League Against Epilepsy (ILAE) and the International Bureau for Epilepsia (IBE) have come to consensus definitions for the terms epileptic seizure and epilepsy.
Abstract: The International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) have come to consensus definitions for the terms epileptic seizure and epilepsy. An epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epileptic seizure.

Journal ArticleDOI
TL;DR: The molecular relationships and physiological functions of these calcium channel proteins are presented and comprehensive information on their molecular, genetic, physiological, and pharmacological properties is provided.
Abstract: The family of voltage-gated sodium channels initiates action potentials in all types of excitable cells. Nine members of the voltage-gated sodium channel family have been characterized in mammals, and a 10th member has been recognized as a related protein. These distinct sodium channels have similar structural and functional properties, but they initiate action potentials in different cell types and have distinct regulatory and pharmacological properties. This article presents the molecular relationships and physiological roles of these sodium channel proteins and provides comprehensive information on their molecular, genetic, physiological, and pharmacological properties.

Journal ArticleDOI
15 Oct 2005-Blood
TL;DR: The new simple index provided valid and reliable scoring of pretransplant comorbidities that predicted nonrelapse mortality and survival and will be useful for clinical trials and patient counseling before HCT.

Journal ArticleDOI
TL;DR: It is concluded that the MPO system plays an important role in the microbicidal activity of phagocytes and the role of theMPO system in tissue injury.
Abstract: Neutrophilic polymorphonuclear leukocytes (neutrophils) are highly specialized for their primary function, the phagocytosis and destruction of microorganisms. When coated with opsonins (generally complement and/or antibody), microorganisms bind to specific receptors on the surface of the phagocyte and invagination of the cell membrane occurs with the incorporation of the microorganism into an intracellular phagosome. There follows a burst of oxygen consumption, and much, if not all, of the extra oxygen consumed is converted to highly reactive oxygen species. In addition, the cytoplasmic granules discharge their contents into the phagosome, and death of the ingested microorganism soon follows. Among the antimicrobial systems formed in the phagosome is one consisting of myeloperoxidase (MPO), released into the phagosome during the degranulation process, hydrogen peroxide (H2O2), formed by the respiratory burst and a halide, particularly chloride. The initial product of the MPO-H2O2-chloride system is hypochlorous acid, and subsequent formation of chlorine, chloramines, hydroxyl radicals, singlet oxygen, and ozone has been proposed. These same toxic agents can be released to the outside of the cell, where they may attack normal tissue and thus contribute to the pathogenesis of disease. This review will consider the potential sources of H2O2 for the MPO-H2O2-halide system; the toxic products of the MPO system; the evidence for MPO involvement in the microbicidal activity of neutrophils; the involvement of MPO-independent antimicrobial systems; and the role of the MPO system in tissue injury. It is concluded that the MPO system plays an important role in the microbicidal activity of phagocytes.

Proceedings ArticleDOI
06 Oct 2005
TL;DR: Opine is introduced, an unsupervised information-extraction system which mines reviews in order to build a model of important product features, their evaluation by reviewers, and their relative quality across products.
Abstract: Consumers are often forced to wade through many on-line reviews in order to make an informed product choice. This paper introduces Opine, an unsupervised information-extraction system which mines reviews in order to build a model of important product features, their evaluation by reviewers, and their relative quality across products.Compared to previous work, Opine achieves 22% higher precision (with only 3% lower recall) on the feature extraction task. Opine's novel use of relaxation labeling for finding the semantic orientation of words in context leads to strong performance on the tasks of finding opinion phrases and their polarity.

Journal ArticleDOI
TL;DR: It is the recommendation of this committee that patients with soft-tissue infection be distinguished by signs and symptoms of systemic toxicity (e.g., fever or hypothermia, tachycardia [heart rate,] and so on).
Abstract: EXECUTIVE SUMMARYSoft-tissue infections are common, generally of mild tomodest severity, and are easily treated with a variety ofagents. An etiologic diagnosis of simple cellulitis is fre-quently difficult and generally unnecessary for patientswith mild signs and symptoms of illness. Clinical as-sessment of the severity of infection is crucial, and sev-eral classification schemes and algorithms have beenproposed to guide the clinician [1]. However, mostclinical assessments have been developed from eitherretrospective studies or from an author’s own “clinicalexperience,” illustrating the need for prospectivestudieswith defined measurements of severity coupled to man-agement issues and outcomes.Until then, it is the recommendation of this com-mittee that patients with soft-tissue infection accom-panied by signs and symptoms of systemic toxicity (e.g.,fever or hypothermia, tachycardia [heart rate,

Journal ArticleDOI
TL;DR: A wide variety of pathogenic microorganisms have been demonstrated to cause eukaryotic cell death, either as a consequence of infecting host cells or by producing toxic products, and apoptosis in many of these systems is characterized as apoptosis.
Abstract: A wide variety of pathogenic microorganisms have been demonstrated to cause eukaryotic cell death, either as a consequence of infecting host cells or by producing toxic products. Pathogen-induced host cell death has been characterized as apoptosis in many of these systems. It is increasingly being

Journal ArticleDOI
TL;DR: The advantages and challenges of polyploidy, and its evolutionary potential, are considered.
Abstract: Polyploids — organisms that have multiple sets of chromosomes — are common in certain plant and animal taxa, and can be surprisingly stable. The evidence that has emerged from genome analyses also indicates that many other eukaryotic genomes have a polyploid ancestry, suggesting that both humans and most other eukaryotes have either benefited from or endured polyploidy. Studies of polyploids soon after their formation have revealed genetic and epigenetic interactions between redundant genes. These interactions can be related to the phenotypes and evolutionary fates of polyploids. Here, I consider the advantages and challenges of polyploidy, and its evolutionary potential.

Journal ArticleDOI
TL;DR: This work introduces “surrogate variable analysis” (SVA) to overcome the problems caused by heterogeneity in expression studies and shows that SVA increases the biological accuracy and reproducibility of analyses in genome-wide expression studies.
Abstract: It has unambiguously been shown that genetic, environmental, demographic, and technical factors may have substantial effects on gene expression levels. In addition to the measured variable(s) of interest, there will tend to be sources of signal due to factors that are unknown, unmeasured, or too complicated to capture through simple models. We show that failing to incorporate these sources of heterogeneity into an analysis can have widespread and detrimental effects on the study. Not only can this reduce power or induce unwanted dependence across genes, but it can also introduce sources of spurious signal to many genes. This phenomenon is true even for well-designed, randomized studies. We introduce “surrogate variable analysis” (SVA) to overcome the problems caused by heterogeneity in expression studies. SVA can be applied in conjunction with standard analysis techniques to accurately capture the relationship between expression and any modeled variables of interest. We apply SVA to disease class, time course, and genetics of gene expression studies. We show that SVA increases the biological accuracy and reproducibility of analyses in genome-wide expression studies.

Journal ArticleDOI
TL;DR: Gene expression analysis showed that IL-2 signaling was required for maintenance of the expression of genes involved in the regulation of cell growth and metabolism, which seems to be critically required for maintaining the homeostasis and competitive fitness of Treg cells in vivo.
Abstract: Regulatory T cells (T(reg) cells) expressing the forkhead family transcription factor Foxp3 are critical mediators of dominant immune tolerance to self. Most T(reg) cells constitutively express the high-affinity interleukin 2 (IL-2) receptor alpha-chain (CD25); however, the precise function of IL-2 in T(reg) cell biology has remained controversial. To directly assess the effect of IL-2 signaling on T(reg) cell development and function, we analyzed mice containing the Foxp3(gfp) knock-in allele that were genetically deficient in either IL-2 (Il2(-/-)) or CD25 (Il2ra(-/-)). We found that IL-2 signaling was dispensable for the induction of Foxp3 expression in thymocytes from these mice, which indicated that IL-2 signaling does not have a nonredundant function in the development of T(reg) cells. Unexpectedly, Il2(-/-) and Il2ra(-/-) T(reg) cells were fully able to suppress T cell proliferation in vitro. In contrast, Foxp3 was not expressed in thymocytes or peripheral T cells from Il2rg(-/-) mice. Gene expression analysis showed that IL-2 signaling was required for maintenance of the expression of genes involved in the regulation of cell growth and metabolism. Thus, IL-2 signaling seems to be critically required for maintaining the homeostasis and competitive fitness of T(reg) cells in vivo.

Journal ArticleDOI
TL;DR: The authors proposed a statistical method for postprocessing ensembles based on Bayesian model averaging (BMA), which is a standard method for combining predictive distributions from different sources, and demonstrated that BMA performs reasonably well when the underlying ensemble is calibrated, or even overdispersed.
Abstract: Ensembles used for probabilistic weather forecasting often exhibit a spread-error correlation, but they tend to be underdispersive. This paper proposes a statistical method for postprocessing ensembles based on Bayesian model averaging (BMA), which is a standard method for combining predictive distributions from different sources. The BMA predictive probability density function (PDF) of any quantity of interest is a weighted average of PDFs centered on the individual bias-corrected forecasts, where the weights are equal to posterior probabilities of the models generating the forecasts and reflect the models’ relative contributions to predictive skill over the training period. The BMA weights can be used to assess the usefulness of ensemble members, and this can be used as a basis for selecting ensemble members; this can be useful given the cost of running large ensembles. The BMA PDF can be represented as an unweighted ensemble of any desired size, by simulating from the BMA predictive distribution. The BMA predictive variance can be decomposed into two components, one corresponding to the between-forecast variability, and the second to the within-forecast variability. Predictive PDFs or intervals based solely on the ensemble spread incorporate the first component but not the second. Thus BMA provides a theoretical explanation of the tendency of ensembles to exhibit a spread-error correlation but yet be underdispersive. The method was applied to 48-h forecasts of surface temperature in the Pacific Northwest in January– June 2000 using the University of Washington fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5) ensemble. The predictive PDFs were much better calibrated than the raw ensemble, and the BMA forecasts were sharp in that 90% BMA prediction intervals were 66% shorter on average than those produced by sample climatology. As a by-product, BMA yields a deterministic point forecast, and this had root-mean-square errors 7% lower than the best of the ensemble members and 8% lower than the ensemble mean. Similar results were obtained for forecasts of sea level pressure. Simulation experiments show that BMA performs reasonably well when the underlying ensemble is calibrated, or even overdispersed.

Journal ArticleDOI
TL;DR: Management of HUS remains supportive; there are no specific therapies to ameliorate the course, and the best way to prevent HUS is to prevent primary infection with Shiga-toxin-producing bacteria.