bluuebunny/crossref_metadata_2025 huggingface dataset:
Satin
Authors: Van Nieuwpoort Rob V. , Wrzesińska Gosia , Jacobs Ceriel J. H. , Bal Henri E.
Published: March 2010

Computational grids have an enormous potential to provide compute power. However, this power remains largely unexploited today for most applications, except trivially parallel programs. Developing parallel grid applications simply is too difficult. Grids introduce several problems not encountered before, mainly due to the highly heterogeneous and dynamic computing and networking environment. Furthermore, failures occur frequently, and resources may be claimed by higher-priority jobs at any time.

In this article, we solve these problems for an important class of applications: divide-and-conquer. We introduce a system called Satin that simplifies the development of parallel grid applications by providing a rich high-level programming model that completely hides communication. All grid issues are transparently handled in the runtime system, not by the programmer. Satin's programming model is based on Java, features spawn-sync primitives and shared objects, and uses asynchronous exceptions and an abort mechanism to support speculative parallelism.

To allow an efficient implementation, Satin consistently exploits the idea that grids are hierarchically structured. Dynamic load-balancing is done with a novel cluster-aware scheduling algorithm that hides the long wide-area latencies by overlapping them with useful local work. Satin's shared object model lets the application define the consistency model it needs. If an application needs only loose consistency, it does not have to pay high performance penalties for wide-area communication and synchronization.

We demonstrate how grid problems such as resource changes and failures can be handled transparently and efficiently. Finally, we show that adaptivity is important in grids. Satin can increase performance considerably by adding and removing compute resources automatically, based on the application's requirements and the utilization of the machines and networks in the grid.

Using an extensive evaluation on real grids with up to 960 cores, we demonstrate that it is possible to provide a simple high-level programming model for divide-and-conquer applications, while achieving excellent performance on grids. At the same time, we show that the divide-and-conquer model scales better on large systems than the master-worker approach, since it has no single central bottleneck.
Formula Caching in DPLL
Authors: Beame Paul , Impagliazzo Russell , Pitassi Toniann , Segerlind Nathan
Published: March 2010

We consider extensions of the DPLL approach to satisfiability testing that add a version ofmemoization, in which formulas that the algorithm has previously shown to be unsatisfiable are remembered for later use. Suchformula cachingalgorithms have been suggested for satisfiability and stochastic satisfiability by several authors. We formalize these methods by developing extensions of the fruitful connection that has previously been developed between DPLL algorithms for satisfiability and tree-like resolution proofs of unsatisfiability. We analyze a number of variants of these formula caching methods and characterize their strength in terms of proof systems. These proof systems are new and simple, and have a rich structure. We compare them to several studied proof systems: tree-like resolution, regular resolution, general resolution, Res(k), and Frege systems and present both simulation and separations. One of our most interesting results is the introduction of a natural and implementable form of DPLL with caching, FCWreason. This system is surprisingly powerful: we prove that it can polynomially simulate regular resolution, and furthermore, it can produce short proofs of some formulas that require exponential-size resolution proofs.
Planarity, Determinants, Permanents, and (Unique) Matchings
Authors: Datta Samir , Kulkarni Raghav , Limaye Nutan , Mahajan Meena
Published: March 2010

Viewing the computation of the determinant and the permanent of integer matrices as combinatorial problems on associated graphs, we explore the restrictiveness of planarity on their complexities and show that both problems remain as hard as in the general case, that is, GapL- and P- complete. On the other hand, both bipartite planarity and bimodal planarity bring the complexity of permanents down (but no further) to that of determinants. The permanent or the determinant modulo 2 is complete for ⊕L, and we show that parity of paths in a layered grid graph (which is bimodal planar) is also complete for this class. We also relate the complexity of grid graph reachability to that of testing existence/uniqueness of a perfect matching in a planar bipartite graph.
SherLog
Authors: Yuan Ding , Mai Haohui , Xiong Weiwei , Tan Lin , Zhou Yuanyuan , Pasupathy Shankar
Published: March 2010

Computer systems often fail due to many factors such as software bugs or administrator errors. Diagnosing such production run failures is an important but challenging task since it is difficult to reproduce them in house due to various reasons: (1) unavailability of users' inputs and file content due to privacy concerns; (2) difficulty in building the exact same execution environment; and (3) non-determinism of concurrent executions on multi-processors.

Therefore, programmers often have to diagnose a production run failure based on logs collected back from customers and the corresponding source code. Such diagnosis requires expert knowledge and is also too time-consuming, tedious to narrow down root causes. To address this problem, we propose a tool, called SherLog, that analyzes source code by leveraging information provided by run-time logs to infer what must or may have happened during the failed production run. It requires neither re-execution of the program nor knowledge on the log's semantics. It infers both control and data value information regarding to the failed execution.

We evaluate SherLog with 8 representative
real world
software failures (6 software bugs and 2 configuration errors) from 7 applications including 3 servers. Information inferred by SherLog are very useful for programmers to diagnose these evaluated failures. Our results also show that SherLog can analyze large server applications such as Apache with thousands of logging messages within only 40 minutes.
Fairness via source throttling
Authors: Ebrahimi Eiman , Lee Chang Joo , Mutlu Onur , Patt Yale N.
Published: March 2010

Cores in a chip-multiprocessor (CMP) system share multiple hardware resources in the memory subsystem. If resource sharing is unfair, some applications can be delayed significantly while others are unfairly prioritized. Previous research proposed separate fairness mechanisms in each individual resource. Such resource-based fairness mechanisms implemented independently in each resource can make contradictory decisions, leading to low fairness and loss of performance. Therefore, a coordinated mechanism that provides fairness in the entire shared memory system is desirable.

This paper proposes a new approach that provides fairness in the
entire shared memory system
, thereby eliminating the need for and complexity of developing fairness mechanisms for each individual resource. Our technique, Fairness via Source Throttling (FST), estimates the unfairness in the entire shared memory system. If the estimated unfairness is above a threshold set by system software, FST throttles down cores causing unfairness by limiting the number of requests they can inject into the system and the frequency at which they do. As such, our
source-based
fairness control ensures fairness decisions are made in tandem in the entire memory system. FST also enforces thread priorities/weights, and enables system software to enforce different fairness objectives and fairness-performance tradeoffs in the memory system.

Our evaluations show that FST provides the best system fairness and performance compared to four systems with no fairness control and with state-of-the-art fairness mechanisms implemented in both shared caches and memory controllers.
An asymmetric distributed shared memory model for heterogeneous parallel systems
Authors: Gelado Isaac , Stone John E. , Cabezas Javier , Patel Sanjay , Navarro Nacho , Hwu Wen-mei W.
Published: March 2010

Heterogeneous computing combines general purpose CPUs with accelerators to efficiently execute both sequential control-intensive and data-parallel phases of applications. Existing programming models for heterogeneous computing rely on programmers to explicitly manage data transfers between the CPU system memory and accelerator memory.

This paper presents a new programming model for heterogeneous computing, called Asymmetric Distributed Shared Memory (ADSM), that maintains a shared logical memory space for CPUs to access objects in the accelerator physical memory but not vice versa. The asymmetry allows light-weight implementations that avoid common pitfalls of symmetrical distributed shared memory systems. ADSM allows programmers to assign data objects to performance critical methods. When a method is selected for accelerator execution, its associated data objects are allocated within the shared logical memory space, which is hosted in the accelerator physical memory and transparently accessible by the methods executed on CPUs.

We argue that ADSM reduces programming efforts for heterogeneous computing systems and enhances application portability. We present a software implementation of ADSM, called GMAC, on top of CUDA in a GNU/Linux environment. We show that applications written in ADSM and running on top of GMAC achieve performance comparable to their counterparts using programmer-managed data transfers. This paper presents the GMAC system and evaluates different design choices. We further suggest additional architectural support that will likely allow GMAC to achieve higher application performance than the current CUDA model.
Inter-core cooperative TLB for chip multiprocessors
Authors: Bhattacharjee Abhishek , Martonosi Margaret
Published: March 2010

Translation Lookaside Buffers (TLBs) are commonly employed in modern processor designs and have considerable impact on overall system performance. A number of past works have studied TLB designs to lower access times and miss rates, specifically for uniprocessors. With the growing dominance of chip multiprocessors (CMPs), it is necessary to examine TLB performance in the context of parallel workloads.

This work is the first to present TLB prefetchers that exploit commonality in TLB miss patterns across cores in CMPs. We propose and evaluate two Inter-Core Cooperative (ICC) TLB prefetching mechanisms, assessing their effectiveness at eliminating TLB misses both individually and together. Our results show these approaches require at most modest hardware and can collectively eliminate 19% to 90% of data TLB (D-TLB) misses across the surveyed parallel workloads.

We also compare performance improvements across a range of hardware and software implementation possibilities. We find that while a fully-hardware implementation results in average performance improvements of 8-46% for a range of TLB sizes, a hardware/software approach yields improvements of 4-32%. Overall, our work shows that TLB prefetchers exploiting inter-core correlations can effectively eliminate TLB misses.
An interview with video quality experts
Authors: Mu Mu
Published: March 2010

Through previous studies in the field, SIGMM members have recognised that research in multimedia must consider aspects of human perception and user preference. Ultimately the improvement of the user level quality-of-experience is more desirable than the more easily measurable quality-of-service.
Topic models for image retrieval on large-scale databases
Authors: Hörster Eva , Lienhart Rainer , Effelsberg Wolfgang , Möller Bernhard
Published: March 2010

With the explosion of the number of images in personal and on-line collections, efficient techniques for navigating, indexing, labeling and searching images become more and more important. In this work we will rely on the image content as the main source of information to retrieve images. We study the representation of images by topic models in its various aspects and extend the current models. Starting from a bag-of-visual-words image description based on local image features, images representations are learned in an unsupervised fashion and each image is modeled as a mixture of topics/object parts depicted in the image. Thus topic models allow us to automatically extract high-level image content descriptions which in turn can be used to find similar images. Further, the typically lowdimensional topic-model-based representation enables efficient and fast search, especially in very large databases.
PPAR/RXR Regulation of Fatty Acid Metabolism and Fatty Acidω‐Hydroxylase (CYP4) Isozymes: Implications for Prevention of Lipotoxicity in Fatty Liver Disease
Authors: Hardwick James P. , Osei-Hyiaman Douglas , Wiland Homer , Abdelmegeed Mohamed A. , Song Byoung-Joon
Published: March 2010

Fatty liver disease is a common lipid metabolism disorder influenced by the combination of individual genetic makeup, drug exposure, and life‐style choices that are frequently associated with metabolic syndrome, which encompasses obesity, dyslipidemia, hypertension, hypertriglyceridemia, and insulin resistant diabetes. Common to obesity related dyslipidemia is the excessive storage of hepatic fatty acids (steatosis), due to a decrease in mitochondriaβ‐oxidation with an increase in both peroxisomalβ‐oxidation, and microsomalω‐oxidation of fatty acids through peroxisome proliferator activated receptors (PPARs). How steatosis increases PPARαactivated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acidβ‐oxidation andω‐oxidation of fatty acids genes regardless of whether dietary fatty acids are polyunsaturated (PUFA), monounsaturated (MUFA), or saturated (SFA) may be determined by the interplay of PPARs and HNF4αwith the fatty acid transport proteins L‐FABP and ACBP. In hepatic steatosis and steatohepatitis, theω‐oxidation cytochrome P450CYP4Agene expression is increased even with reduced hepatic levels of PPARα. Although numerous studies have suggested the role ethanol‐inducibleCYP2E1in contributing to increased oxidative stress,Cyp2e1‐null mice still develop steatohepatitis with a dramatic increase inCYP4Agene expression. This strongly implies thatCYP4Afatty acidω‐hydroxylase P450s may play an important role in the development of steatohepatitis. In this review and tutorial, we briefly describe how fatty acids are partitioned by fatty acid transport proteins to either anabolic or catabolic pathways regulated by PPARs, and we explore how medium‐chain fatty acid (MCFA)CYP4Aand long‐chain fatty acid (LCFA)CYP4Fω‐hydroxylase genes are regulated in fatty liver. We finally propose a hypothesis that increasedCYP4Aexpression with a decrease inCYP4Fgenes may promote the progression of steatosis to steatohepatitis.
Several New Aspects of the Foraging Behavior ofOsmia cornifronsin an Apple Orchard
Authors: Matsumoto Shogo , Maejima Tsutomu
Published: March 2010

We investigated the foraging behavior ofOsmia cornifronsRadoszkowski, which is a useful pollinator in apple orchards consisting of only one kind of commercial cultivars such as “Fuji”, and of different types of pollinizers, such as the red petal type, “Maypole” or “Makamik”. It was confirmed that, in terms of the number of foraging flowers per day, visiting flowers during low temperatures, strong wind, and reduced sunshine in an apple orchard,O. cornifronswere superior to honeybees. We indicated thatO. cornifronsseemed to use both petals and anthers as foraging indicator, and that not only female, but also males contributed to apple pollination and fertilization by the pollen grains attached to them from visiting flowers, including those at the balloon stage. It was confirmed thatO. cornifronsacts as a useful pollinator in an apple orchard consisting of one kind of cultivar with pollinizers planted not more than 10 m from commercial cultivars.
Explaining Gender Differences in Caries: A Multifactorial Approach to a Multifactorial Disease
Authors: Ferraro Maria , Vieira Alexandre R.
Published: March 2010

Many studies have demonstrated that caries rates are higher in women than in men. This review attempts to provide an explanation for this trend by examining each factor which contributes to caries and how the factor differs in men and women. Evidence has been provided to demonstrate that caries risk factors for women include a different salivary composition and flow rate, hormonal fluctuations, dietary habits, genetic variations, and particular social roles among their family. Systemic diseases that have been found to be associated with caries have also been found to have an association with the female gender. An extended exposure to the oral cavity or a more cariogenic oral microflora has not been proven to contribute to higher caries in women. Further research in these areas could be done in the future to explain their contribution, or lack thereof, to a higher caries rate in women.
Use of Alternative Tobacco Products in Multiethnic Youth from Jujuy, Argentina
Authors: Alderete Ethel , Kaplan Celia Patricia , Gregorich Steven E. , Pérez-Stable Eliseo J.
Published: March 2010

This study examines alternative tobacco use among Latin American youth. A self-administered survey in a random sample of 27 schools was administered in 2004 in Jujuy, Argentina (N=3218). Prevalence of alternative tobacco product use was 24.1%; 15.3% of youth used hand-rolled cigarettes, 7.8% smoked cigars, 2.3% chewed tobacco leaf and 1.6% smoked pipe. Among youth who never smoked manufactured cigarettes, alternative product use was rare (2.9%), except for chewing tobacco (22%). In multivariate logistic regression boys were more likely than girls to smoke pipe (OR = 3.1; 95% CI 1.1–8.7); indigenous language was associated with smoking hand-rolled cigarettes (OR = 1.4; 95% CI-1.1–1.9) and pipe (OR = 2.2; 95% CI 1.5–3.4). Working in tobacco sales was a risk factor for chewing tobacco (OR = 2.9; 95% CI: 1.7–4.9) and smoking hand-rolled cigarettes (OR = 1.4; 95% CI 1.1–1.8). Having friends who smoked was associated with chewing tobacco (OR = 1.8; 95% CI 1.0–3.2) and with smoking cigars (OR = 2.1; 95% CI 1.5–2.9). Current drinking and thrill-seeking orientation were associated with cigars and pipe smoking. Findings highlight the importance of surveillance of alternative tobacco products use and availability among youth and for addressing identified risk factors.
Metabolic and Cardiovascular Effects of Ghrelin
Authors: Tesauro Manfredi , Schinzari Francesca , Caramanti Miriam , Lauro Renato , Cardillo Carmine
Published: March 2010

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is synthesized as a preprohormone and then proteolytically processed to yield a 28-amino acid peptide.
This peptide was originally reported to induce growth hormone release; large evidence, however, has indicated many other physiological activities of ghrelin, including regulation of food intake and energy balance, as well as of lipid and glucose metabolism.
Ghrelin receptors have been detected in the hypothalamus and the pituitary, but also in the cardiovascular system, where ghrelin exerts beneficial hemodynamic activities. Ghrelin administration acutely improves endothelial dysfunction by increasing nitric oxide bioavailability and normalizes the altered balance between endothelin-1 and nitric oxide within the vasculature of patients with metabolic syndrome. Other cardiovascular effects of ghrelin include improvement of left ventricular contractility and cardiac output, as well as reduction of arterial pressure and systemic vascular resistance. In addition, antinflammatory and antiapoptotic actions of ghrelin have been reported both in vivo and in vitro.
This review summarizes the most recent findings on the metabolic and cardiovascular effects of ghrelin through GH-dependent and -independent mechanisms and the possible role of ghrelin as a therapeutic molecule for treating cardiovascular diseases.
Effect of Bifidobacterium lactis on the Incidence of Nosocomial Infections in Very-Low-Birth-Weight Infants: A Randomized Controlled Trial
Authors: Mihatsch W.A. , Vossbeck S. , Eikmanns B. , Hoegel J. , Pohlandt F.
Published: March 2010

Background: Nosocomial infections endanger preterm infants. Objective: The aim of the present controlled randomized trial was to investigate whether Bifidobacterium lactis reduces the incidence of nosocomial infections in infants with very low birth weight (VLBW; <1,500 g) <30 weeks of gestation. Patients and Methods: In a randomized controlled trial, 183 VLBW infants <30 weeks of gestation were stratified according to gestational age (23–26 and 27–29 weeks) and early antibiotic therapy (days 1–3, yes or no) and randomly assigned to have their milk feedings supplemented with B. lactis (6 × 2.0 × 109 CFU/kg/day, 12 billion CFU/kg/day) or placebo for the first 6 weeks of life. Primary outcome was the ‘incidence density’ of nosocomial infections defined as periods of elevated C-reactive protein (>10 mg/l) from day 7 after initiation of milk feedings until the 42nd day of life (number of nosocomial infections/total number of patient days). The main secondary outcome was necrotizing enterocolitis (NEC; ≧stage 2). Results: There were 93 infants in the B. lactis group and 90 in the placebo group. There was no significant difference between the two groups with regard to the incidence density of nosocomial infections (0.021 vs. 0.016; p = 0.9, χ2 test). There were 2 cases of NEC in the B. lactis group and 4 in the placebo group. None of the blood cultures grew B. lactis. Conclusion: In the present setting, B. lactis at a dosage of 6 × 2.0 × 109 CFU/kg/day (12 billion CFU/kg/day) did not reduce the incidence density of nosocomial infections in VLBW infants. No adverse effect of B. lactis was observed.
Maturation of Adrenal Function Determined by Urinary Glucocorticoid Steroid Excretion Rates in Preterm Infants of More than 30 Weeks of Gestational Age
Authors: Grofer Bianka , Bödeker Rolf-Hasso , Gortner Ludwig , Heckmann Matthias
Published: March 2010

Background: Data on the adrenal stress response of preterm infants between 30 and 36 weeks are inconsistent. Objective: To test the hypothesis that there is a positive association between illness severity and cortisol production rates (CPR) in preterm infants >30 weeks. Patients and Methods: In a prospective longitudinal observational study, glucocorticoid metabolites were profiled by gas chromatography-mass spectrometry in 24-hour urinary samples. Excretion rates of glucocorticoid metabolites were summed to calculate CPR in 61 well (mean ± SD: 33.6 ± 1.7 weeks) and 20 ill (33.2 ± 1.6 weeks) preterm infants. Illness severity was measured by the score for neonatal acute physiology (SNAP). Results: During the first week of life, SNAP were higher in the group of ill compared to well infants. Medians of CPR (µg/kg/d per mg creatinine) in ill (well) infants were: 1st day, 31 (28); 2nd day, 24 (28); 3rd day, 27 (26); 5th day, 28 (17); 2nd week, 20 (19); 3rd week, 17 (19); 4th week, 16 (16); and 2nd month, 17 (23). There was a significant association between the maximum of SNAP and the maximum of CPR (OR 3.7; 95% CI: 1.2–11.5; p = 0.02) in a logistic regression model which comprised gestational age, mode of delivery, gender and the administration of prenatal steroids as covariables. Conclusion: There was a positive association between severity of illness and CPR in preterm infants >30 weeks, indicating a maturation of the adrenal stress response.
Elevated Brain Natriuretic Peptide Is Associated with Abnormal Heart Geometry in Children with Chronic Kidney Disease
Authors: Hedvig J. , Podracká Ľ. , Potočeková D.
Published: March 2010

Aim: It was to establish whether brain natriuretic peptide (BNP) might predict cardiac dysfunction in children with chronic kidney disease (CKD). Methods: The relation between BNP, echocardiography and risk factors (hypertension, anemia, lipids, CRP, hyperparathyroidism) was investigated in 46 children (10 pre-dialysis patients, 14 on dialysis, 11 children with kidney transplants, and 11 healthy controls). Data on BNP were transformed into common logarithms (log10 BNP, log BNP). Results: log BNP was significantly higher in dialysis patients when compared to controls (2.09 ± 0.78 vs. 1.43 ± 0.34 pg/ml, p = 0.012) and patients in the pre-dialysis stage (2.09 ± 0.78 vs. 1.52 ± 0.42 pg/ml, p = 0.039). log BNP in transplanted children was not significantly different from healthy children (2.09 ± 0.78 vs. 1.71 ± 0.46 pg/ml, p = 0.19). Abnormal heart geometry (concentric and eccentric hypertrophy, concentric remodeling) was found in 19 patients (54.28%). A significant correlation was observed between log BNP and ventricular hypertrophy (r = 0.515, p = 0.001). Compared to controls higher log BNP was seen in children with eccentric hypertrophy than in children with concentric hypertrophy (2.178 ± 0.956 vs. 1.496 ± 0.395 pg/ml, p = 0.05, or 1.982 ± 0.618 vs. 1.496 ± 0.395, p = 0.04). Conclusions: BNP might predict an abnormal geometry in children with CKD.
Delays of Event Adjudication in the TRITON Trial
Authors: Serebruany Victor L.
Published: March 2010

Background: Central adjudication of clinical events in randomized controlled trials represents an attractive but still controversial approach since the adjudicated data usually match well with the investigator-reported event rates but increase affiliated costs. Purpose: The aim was to assess the timing of clinical event adjudication in the TRITON trial. Methods: A review of the FDA action package for prasugrel was conducted. Results: Adjudications for deaths and strokes were distributed evenly throughout the study period. Bleeding event adjudications were performed predominantly in the later stages of the study. Adjudications for myocardial infarction and especially stent thrombosis were significantly delayed. Conclusions: Among all clinical events, only deaths and strokes in TRITON were adjudicated without delays. Late adjudication of myocardial infarction and stent thrombosis are uncommon but at least can be explained by lack or change of event definitions. However, the delays with adjudications of revascularization procedures and especially timely recording of bleeding complications lack reasonable explanation. The regulatory authorities should consider independent audits when there is a major disagreement between centrally adjudicated and site-reported events influencing the results of a major clinical trial.
Atorvastatin Reduces Plaque Vulnerability in an Atherosclerotic Rabbit Model by Altering the 5-Lipoxygenase Pathway
Authors: Zhou Guangyi , Ge Song , Liu Dezhi , Xu Gelin , Zhang Renliang , Yin Qin , Zhu Wusheng , Chen Jieli , Liu Xinfeng
Published: March 2010

Objective: The 5-lipoxygenase catalyzed formation of leukotriene lipid mediators is a mediator for inflammatory response in arteries. The present study investigated the relationship between atorvastatin and the 5-lipoxygenase pathway in an atherosclerotic rabbit model. Methods: Thirty male New Zealand White Rabbits were randomized into negative control, positive control and atorvastatin groups. At week 4, the rabbits were subjected to carotid balloon-dilation injury or carotid balloon-dilation injury, followed by treatment with atorvastatin. At week 12, all the animals were sacrificed. Plasma lipids, LTD4, and 15-epi-lipoxin A4 were measured using the enzymatic endpoint method and ELISA, respectively. RT-PCR was performed to detect the gene expression of 5-lipoxygenase-activating protein and cysLT1R in rabbit carotid arteries. Finally, histological analysis was used to evaluate the pathophysiological changes of rabbit carotid arteries. Results: The results showed atorvastatin markedly lowered serum lipids and LTD4 levels compared with the control group. Similarly, mRNA expression of 5-lipoxygenase-activating protein and cysLT1R was significantly inhibited by atorvastatin. Decreased carotid plaque instability was evident in atorvastatin-treated animals, as demonstrated by a thickened elastic layer, less neointima hyperplasia and macrophage proliferation. Conclusions: Atorvastatin may stabilize carotid plaque by regulating the 5-lipoxygenase pathway in atherosclerotic rabbits and delay the progression of atherosclerosis by exerting anti-inflammatory effects.
Physical Activity, Health Status and Risk of Hospitalization in Patients with Severe Chronic Obstructive Pulmonary Disease
Authors: Benzo Roberto P. , Chang Chung-Chou H. , Farrell Max H. , Kaplan Robert , Ries Andrew , Martinez Fernando J. , Wise Robert , Make Barry , Sciurba Frank ,   for the NETT Research Group
Published: March 2010

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of death and 70% of the cost of COPD is due to hospitalizations. Self-reported daily physical activity and health status have been reported as predictors of a hospitalization in COPD but are not routinely assessed. Objectives: We tested the hypothesis that self-reported daily physical activity and health status assessed by a simple question were predictors of a hospitalization in a well-characterized cohort of patients with severe emphysema. Methods: Investigators gathered daily physical activity and health status data assessed by a simple question in 597 patients with severe emphysema and tested the association of those patient-reported outcomes to the occurrence of a hospitalization in the following year. Multiple logistic regression analyses were used to determine predictors of hospitalization during the first 12 months after randomization. Results: The two variables tested in the hypothesis were significant predictors of a hospitalization after adjusting for all univariable significant predictors: >2 h of physical activity per week had a protective effect [odds ratio (OR) 0.60; 95% confidence interval (95% CI) 0.41–0.88] and self-reported health status as fair or poor had a deleterious effect (OR 1.57; 95% CI 1.10–2.23). In addition, two other variables became significant in the multivariate model: total lung capacity (every 10% increase) had a protective effect (OR 0.88; 95% CI 0.78–0.99) and self-reported anxiety had a deleterious effect (OR 1.75; 95% CI 1.13–2.70). Conclusion: Self-reported daily physical activity and health status are independently associated with COPD hospitalizations. Our findings, assessed by simple questions, suggest the value of patient-reported outcomes in developing risk assessment tools that are easy to use.
Monocytes and Macrophages Regulate Immunity through Dynamic Networks of Survival and Cell Death
Authors: Parihar Arti , Eubank Timothy D. , Doseff Andrea I.
Published: March 2010

Monocytes and macrophages are central cells of the innate immune system, responsible for defending against diverse pathogens. While they originate from a common myeloid precursor and share functions in innate immunity, each has a very distinct life span finely tuned by the apoptotic caspases. Normally, circulating monocytes are short-lived and undergo spontaneous apoptosis on a daily basis. Macrophages, however, have a longer life span. In chronic inflammatory diseases and, as recently recognized, in the tumor microenvironment, the inhibition of the apoptotic program promotes monocyte survival contributing to the accumulation of macrophages and the persistence of an inflammatory milieu. A complex network of differentiation factors and inflammatory stimuli determine monocyte/macrophage life span by blocking the apoptotic pathway and activating a myriad of survival pathways. Our understanding of apoptosis has flourished over the last decade, and its relevance in the regulation of the immune system is now indisputable. Nevertheless, how the complicated networks of survival and apoptotic regulators are integrated to determine cellular life span remains elusive. This review summarizes the contribution of the caspases and their regulators in monocyte/macrophage cell fate and discusses how these molecules orchestrate the initiation, maintenance, and resolution of inflammation. More provocatively, we discuss possible strategies to control inflammation by manipulating leukocyte life span.
Prognostic Implications of Left Ventricular Filling Pressure With Exercise
Authors: Holland David J. , Prasad Sandhir B. , Marwick Thomas H.
Published: March 2010

Background—

The estimation of left ventricular (LV) filling pressure from the ratio of transmitral and annular velocities (E/e′) after exercise echocardiography may identify diastolic dysfunction in patients who complain of exertional dyspnea. This study sought to determine the relative contributions of exercise E/e′ and ischemia to outcomes in patients referred for exercise echocardiography.

Methods and Results—

Rest and exercise E/e′ were obtained in 522 patients referred for exercise echocardiography, who were followed for cardiovascular death and hospitalization over a median of 13.2 months. Exercise E/e′ >2 SD from normal was used to denote raised LV filling pressure with stress (n=75), and ischemia (n=250) was identified by inducible wall motion abnormalities. There were 65 cardiovascular hospitalizations during the follow-up period. Survival analysis showed patients without ischemia and with normal exercise E/e′ to have a better prognosis than those with ischemia, with or without raised exercise E/e′ (
P
=0.003) and the outcomes of patients with isolated raised exercise E/e′ and isolated ischemia to be similar. Exercise E/e′ was most valuable in patients with normal resting E/e′; those with elevation with exercise had a worse outcome than those with normal exercise E/e′ (
P
=0.014). Exercise capacity (hazard ratio, 0.893;
P
=0.008), exercise wall motion score index (hazard ratio, 1.507;
P
<0.001), and exercise E/e′ >14.5 (hazard ratio, 2.988;
P
=0.002) were independent predictors of outcome. The addition of exercise E/e′ to exercise capacity and wall motion score index resulted in an increment in model power to predict adverse outcome (
P
=0.006).

Conclusions—

Exercise E/e′ is associated with cardiovascular hospitalization, independent of and incremental to inducible ischemia.
Novel Associations of Multiple Genetic Loci With Plasma Levels of Factor VII, Factor VIII, and von Willebrand Factor
Authors: Smith Nicholas L. , Chen Ming-Huei , Dehghan Abbas , Strachan David P. , Basu Saonli , Soranzo Nicole , Hayward Caroline , Rudan Igor , Sabater-Lleal Maria , Bis Joshua C. , de Maat Moniek P.M. , Rumley Ann , Kong Xiaoxiao , Yang Qiong , Williams Frances M.K. , Vitart Veronique , Campbell Harry , Mälarstig Anders , Wiggins Kerri L. , Van Duijn Cornelia M. , McArdle Wendy L. , Pankow James S. , Johnson Andrew D. , Silveira Angela , McKnight Barbara , Uitterlinden Andre G. ,   Wellcome Trust Case Control Consortium;, Aleksic Nena , Meigs James B. , Peters Annette , Koenig Wolfgang , Cushman Mary , Kathiresan Sekar , Rotter Jerome I. , Bovill Edwin G. , Hofman Albert , Boerwinkle Eric , Tofler Geoffrey H. , Peden John F. , Psaty Bruce M. , Leebeek Frank , Folsom Aaron R. , Larson Martin G. , Spector Timothy D. , Wright Alan F. , Wilson James F. , Hamsten Anders , Lumley Thomas , Witteman Jacqueline C.M. , Tang Weihong , O'Donnell Christopher J.
Published: March 2010

Background—

Plasma levels of coagulation factors VII (FVII), VIII (FVIII), and von Willebrand factor (vWF) influence risk of hemorrhage and thrombosis. We conducted genome-wide association studies to identify new loci associated with plasma levels.

Methods and Results—

The setting of the study included 5 community-based studies for discovery comprising 23 608 European-ancestry participants: Atherosclerosis Risk In Communities Study, Cardiovascular Health Study, British 1958 Birth Cohort, Framingham Heart Study, and Rotterdam Study. All subjects had genome-wide single-nucleotide polymorphism (SNP) scans and at least 1 phenotype measured: FVII activity/antigen, FVIII activity, and vWF antigen. Each study used its genotype data to impute to HapMap SNPs and independently conducted association analyses of hemostasis measures using an additive genetic model. Study findings were combined by meta-analysis. Replication was conducted in 7604 participants not in the discovery cohort. For FVII, 305 SNPs exceeded the genome-wide significance threshold of 5.0×10
−8
and comprised 5 loci on 5 chromosomes: 2p23 (smallest
P
value 6.2×10
−24
), 4q25 (3.6×10
−12
), 11q12 (2.0×10
−10
), 13q34 (9.0×10
−259
), and 20q11.2 (5.7×10
−37
). Loci were within or near genes, including 4 new candidate genes and
F7
(13q34). For vWF, 400 SNPs exceeded the threshold and marked 8 loci on 6 chromosomes: 6q24 (1.2×10
−22
), 8p21 (1.3×10
−16
), 9q34 (<5.0×10
−324
), 12p13 (1.7×10
−32
), 12q23 (7.3×10
−10
), 12q24.3 (3.8×10
−11
), 14q32 (2.3×10
−10
), and 19p13.2 (1.3×10
−9
). All loci were within genes, including 6 new candidate genes, as well as
ABO
(9q34) and
VWF
(12p13). For FVIII, 5 loci were identified and overlapped vWF findings. Nine of the 10 new findings were replicated.

Conclusions—

New genetic associations were discovered outside previously known biological pathways and may point to novel prevention and treatment targets of hemostasis disorders.
B Vitamins and the Risk of Total Mortality and Cardiovascular Disease in End-Stage Renal Disease
Authors: Heinz Judith , Kropf Siegfried , Domröse Ute , Westphal Sabine , Borucki Katrin , Luley Claus , Neumann Klaus H. , Dierkes Jutta
Published: March 2010

Background—

In observational studies, hyperhomocysteinemia has been found to be a risk factor for total mortality and cardiovascular events in patients with end-stage renal disease. These patients have grossly elevated homocysteine levels that can be lowered by supplementation with folic acid and vitamin B
12
. We conducted a randomized clinical trial with B vitamins to reduce homocysteine levels and therefore cardiovascular events and total mortality.

Methods and Results—

This randomized, double-blind multicenter study was conducted in 33 dialysis centers in north and east Germany between July 2002 and July 2008. We randomly assigned 650 patients with end-stage renal disease who were undergoing hemodialysis to 2 postdialysis treatments: 5 mg folic acid, 50 μg vitamin B
12
, and 20 mg vitamin B
6
(active treatment) or 0.2 mg folic acid, 4 μg vitamin B
12
, and 1.0 mg vitamin B
6
(placebo) given 3 times per week for an average of 2 years. The primary outcome was total mortality; the secondary outcome was fatal and nonfatal cardiovascular events. The primary outcome occurred in 102 patients (31%) receiving the active treatment and in 92 (28%) receiving placebo (hazard ratio, 1.13; 95% confidence interval, 0.85 to 1.50;
P
=0.51). The secondary outcome occurred in 83 patients (25%) receiving the active treatment and in 98 (30%) receiving placebo (hazard ratio, 0.80; 95% confidence interval, 0.60 to 1.07;
P
=0.13).

Conclusions—

Increased intake of folic acid, vitamin B
12
, and vitamin B
6
did not reduce total mortality and had no significant effect on the risk of cardiovascular events in patients with end-stage renal disease.

Clinical Trial Registration—

URL: www.anzctr.org.au. Unique identifier: ACTRN12609000911291. URL: www.cochrane-renal.org. Unique identifier: CRG010600027.
Mode of Death in Patients With Heart Failure and a Preserved Ejection Fraction
Authors: Zile Michael R. , Gaasch William H. , Anand Inder S. , Haass Markus , Little William C. , Miller Alan B. , Lopez-Sendon Jose , Teerlink John R. , White Michel , McMurray John J. , Komajda Michel , McKelvie Robert , Ptaszynska Agata , Hetzel Scott J. , Massie Barry M. , Carson Peter E.
Published: March 2010

Background—

The mode of death has been well characterized in patients with heart failure and a reduced ejection fraction; however, less is known about the mode of death in patients with heart failure and a preserved ejection fraction (HFPEF). The purpose of this study was to examine the mode of death in patients with HFPEF enrolled in the Irbesartan in Heart Failure With Preserved Ejection Fraction Study (I-Preserve) trial and to determine whether irbesartan altered the distribution of mode of death in HFPEF.

Methods and Results—

All deaths were reviewed by a clinical end-point committee, and the mode of death was assigned by consensus of the members. The annual mortality rate was 5.2% in the I-Preserve trial. There were no significant differences in mortality rate between the placebo and irbesartan groups. The mode of death was cardiovascular in 60% (including 26% sudden, 14% heart failure, 5% myocardial infarction, and 9% stroke), noncardiovascular in 30%, and unknown in 10%. There were no differences in the distribution of mode-specific mortality rates between placebo and irbesartan.

Conclusions—

Sixty percent of the deaths in patients with HFPEF were cardiovascular, with sudden death and heart failure death being the most common. Treatment with irbesartan did not affect overall mortality or the distribution of mode-specific mortality rates.

Clinical Trial Registration—

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238.
Whole Genome Survey of Copy Number Variation in the Spontaneously Hypertensive Rat
Authors: Charchar Fadi J. , Kaiser Michael , Bingham Andrew J. , Fotinatos Nina , Ahmady Fahima , Tomaszewski Maciej , Samani Nilesh J.
Published: March 2010

Copy number variation has emerged recently as an important genetic mechanism leading to phenotypic heterogeneity. The aim of our study was to determine whether copy number variants (CNVs) exist between the spontaneously hypertensive rat (SHR) and its control strain, the Wistar-Kyoto rat, whether these map to quantitative trait loci in the rat and whether CNVs associate with gene expression or blood pressure differences between the 2 strains. We performed a comparative genomic hybridization assay between SHR and Wistar-Kyoto strains using a whole-genome array. In total, 16 CNVs were identified and validated (6 because of a relative loss of copy number in the SHR and 10 because of a relative gain). CNVs were present on rat autosomes 1, 3, 4, 6, 7, 10, 14, and 17 and varied in size from 10.0 kb to 1.6 Mb. Most of these CNVs mapped to chromosomal regions within previously identified quantitative trait loci, including those for blood pressure in the SHR. Transcriptomic experiments confirmed differences in the renal expression of several genes (including Ms4a6a, Ndrg3, Egln1, Cd36, Sema3a, Ugt2b, and Idi21) located in some of the CNVs between SHR and Wistar-Kyoto rats. In F
2
animals derived from an SHR×Wistar-Kyoto cross, we also found a significant increase in blood pressure associated with an increase in copy number in the Egln1 gene. Our findings suggest that CNVs may play a role in the susceptibility to hypertension and related traits in the SHR.
Effect of the Urotensin Receptor Antagonist Palosuran in Hypertensive Patients With Type 2 Diabetic Nephropathy
Authors: Vogt Liffert , Chiurchiu Carlos , Chadha-Boreham Harbajan , Danaietash Parisa , Dingemanse Jasper , Hadjadj Samy , Krum Henry , Navis Gerjan , Neuhart Eric , Parvanova Aneliya I. , Ruggenenti Piero , Woittiez Arend Jan , Zimlichman Reuven , Remuzzi Giuseppe , de Zeeuw Dick
Published: March 2010

The urotensin system has been hypothesized to play an important role in the pathophysiology of diabetic nephropathy. In this multicenter, randomized, double-blind, placebo-controlled, 2-period crossover study, the effects of the urotensin receptor antagonist palosuran on urinary albumin excretion and blood pressure in hypertensive patients with type 2 diabetic nephropathy treated with a single blocker of the renin-angiotensin-aldosterone system were assessed. Patients with 24-hour albuminuria >0.5 and <3.0 g, systolic blood pressure >135 and <170 mm Hg, and/or diastolic blood pressure >85 and <110 mm Hg received both palosuran 125 mg BID and placebo for 4 weeks each. Fifty-four patients (20% women; mean age: 61.6 years, blood pressure: 155/84 mm Hg, and albuminuria: 1016 mg per 24 hours) were included in the per-protocol analysis. Palosuran did not affect albuminuria, blood pressure, glomerular filtration rate, or renal plasma flow significantly. These results question whether urotensin receptor antagonism represents a new treatment strategy in this high-risk patient population.
Modulation of Internal Gravity Waves in a Multiscale Model for Deep Convection on Mesoscales
Authors: Ruprecht Daniel , Klein Rupert , Majda Andrew J.
Published: March 2010

Starting from the conservation laws for mass, momentum, and energy together with a three-species bulk microphysics model, a model for the interaction of internal gravity waves and deep convective hot towers is derived using multiscale asymptotic techniques. From the leading-order equations, a closed model for the large-scale flow is obtained analytically by applying horizontal averages conditioned on the small-scale hot towers. No closure approximations are required besides adopting the asymptotic limit regime on which the analysis is based. The resulting model is an extension of the anelastic equations linearized about a constant background flow. Moist processes enter through the area fraction of saturated regions and through two additional dynamic equations describing the coupled evolution of the conditionally averaged small-scale vertical velocity and buoyancy. A two-way coupling between the large-scale dynamics and these small-scale quantities is obtained: moisture reduces the effective stability for the large-scale flow, and microscale up- and downdrafts define a large-scale averaged potential temperature source term. In turn, large-scale vertical velocities induce small-scale potential temperature fluctuations due to the discrepancy in effective stability between saturated and nonsaturated regions.

The dispersion relation and group velocity of the system are analyzed and moisture is found to have several effects: (i) it reduces vertical energy transport by waves, (ii) it increases vertical wavenumbers but decreases the slope at which wave packets travel, (iii) it introduces a new lower horizontal cutoff wavenumber in addition to the well-known high wavenumber cutoff, and (iv) moisture can cause critical layers. Numerical examples reveal the effects of moisture on steady-state and time-dependent mountain waves in the present hot-tower regime.
A Comparative Verification of Localized Aviation Model Output Statistics Program (LAMP) and Numerical Weather Prediction (NWP) Model Forecasts of Ceiling Height and Visibility
Authors: Rudack David E. , Ghirardelli Judy E.
Published: March 2010

In an effort to support aviation forecasting, the National Weather Service’s Meteorological Development Laboratory (MDL) has recently redeveloped the Localized Aviation Model Output Statistics (MOS) Program (LAMP) system. LAMP is designed to run hourly in NWS operations and produce short-range aviation forecast guidance at 1-h projections out to 25 h. This paper compares and contrasts LAMP ceiling height and visibility forecasts with forecasts produced by the 20-km Rapid Update Cycle model (RUC20), the Weather Research and Forecasting Nonhydrostatic Mesoscale Model (WRF-NMM), and the Short-Range Ensemble Forecast system (SREF). RUC20 and WRF-NMM forecasts of continuous ceiling height and visibility were interpolated to stations and converted into categorical forecasts. These interpolated forecasts were also categorized into instrument flight rule (IFR) or lower conditions and verified against LAMP forecasts at stations in the contiguous United States. LAMP and SREF probabilistic forecasts of ceiling height and visibility from LAMP and the SREF system were also verified. This study demonstrates that for the 0000 and 1200 UTC cycles over the contiguous United States, LAMP station-based categorical forecasts of ceiling height, visibility, and IFR conditions or lower are more accurate than the RUC20 and WRF-NMM ceiling height and visibility forecasts interpolated to stations. Moreover, for the 0900 and 2100 UTC forecast cycles and verification periods studied here, LAMP ceiling height and visibility probabilities exhibit better reliability and skill than the SREF system.