scispace - formally typeset
Search or ask a question

Showing papers by "Brown University published in 2009"


Journal ArticleDOI
TL;DR: In this article, the Wilkinson Microwave Anisotropy Probe (WMAP) 5-year data were used to constrain the physics of cosmic inflation via Gaussianity, adiabaticity, the power spectrum of primordial fluctuations, gravitational waves, and spatial curvature.
Abstract: The Wilkinson Microwave Anisotropy Probe (WMAP) 5-year data provide stringent limits on deviations from the minimal, six-parameter Λ cold dark matter model. We report these limits and use them to constrain the physics of cosmic inflation via Gaussianity, adiabaticity, the power spectrum of primordial fluctuations, gravitational waves, and spatial curvature. We also constrain models of dark energy via its equation of state, parity-violating interaction, and neutrino properties, such as mass and the number of species. We detect no convincing deviations from the minimal model. The six parameters and the corresponding 68% uncertainties, derived from the WMAP data combined with the distance measurements from the Type Ia supernovae (SN) and the Baryon Acoustic Oscillations (BAO) in the distribution of galaxies, are: Ω b h 2 = 0.02267+0.00058 –0.00059, Ω c h 2 = 0.1131 ± 0.0034, ΩΛ = 0.726 ± 0.015, ns = 0.960 ± 0.013, τ = 0.084 ± 0.016, and at k = 0.002 Mpc-1. From these, we derive σ8 = 0.812 ± 0.026, H 0 = 70.5 ± 1.3 km s-1 Mpc–1, Ω b = 0.0456 ± 0.0015, Ω c = 0.228 ± 0.013, Ω m h 2 = 0.1358+0.0037 –0.0036, z reion = 10.9 ± 1.4, and t 0 = 13.72 ± 0.12 Gyr. With the WMAP data combined with BAO and SN, we find the limit on the tensor-to-scalar ratio of r 1 is disfavored even when gravitational waves are included, which constrains the models of inflation that can produce significant gravitational waves, such as chaotic or power-law inflation models, or a blue spectrum, such as hybrid inflation models. We obtain tight, simultaneous limits on the (constant) equation of state of dark energy and the spatial curvature of the universe: –0.14 < 1 + w < 0.12(95%CL) and –0.0179 < Ω k < 0.0081(95%CL). We provide a set of WMAP distance priors, to test a variety of dark energy models with spatial curvature. We test a time-dependent w with a present value constrained as –0.33 < 1 + w 0 < 0.21 (95% CL). Temperature and dark matter fluctuations are found to obey the adiabatic relation to within 8.9% and 2.1% for the axion-type and curvaton-type dark matter, respectively. The power spectra of TB and EB correlations constrain a parity-violating interaction, which rotates the polarization angle and converts E to B. The polarization angle could not be rotated more than –59 < Δα < 24 (95% CL) between the decoupling and the present epoch. We find the limit on the total mass of massive neutrinos of ∑m ν < 0.67 eV(95%CL), which is free from the uncertainty in the normalization of the large-scale structure data. The number of relativistic degrees of freedom (dof), expressed in units of the effective number of neutrino species, is constrained as N eff = 4.4 ± 1.5 (68%), consistent with the standard value of 3.04. Finally, quantitative limits on physically-motivated primordial non-Gaussianity parameters are –9 < f local NL < 111 (95% CL) and –151 < f equil NL < 253 (95% CL) for the local and equilateral models, respectively.

5,904 citations


Journal ArticleDOI
TL;DR: These updated guidelines replace the previous management guidelines published in 2001 and are intended for use by health care providers who care for patients who either have these infections or may be at risk for them.
Abstract: These updated guidelines replace the previous management guidelines published in 2001. The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them.

2,828 citations


Journal ArticleDOI
24 Apr 2009-Science
TL;DR: What is known and what is needed to develop a holistic understanding of the role of fire in the Earth system are reviewed, particularly in view of the pervasive impact of fires and the likelihood that they will become increasingly difficult to control as climate changes.
Abstract: Fire is a worldwide phenomenon that appears in the geological record soon after the appearance of terrestrial plants. Fire influences global ecosystem patterns and processes, including vegetation distribution and structure, the carbon cycle, and climate. Although humans and fire have always coexisted, our capacity to manage fire remains imperfect and may become more difficult in the future as climate change alters fire regimes. This risk is difficult to assess, however, because fires are still poorly represented in global models. Here, we discuss some of the most important issues involved in developing a better understanding of the role of fire in the Earth system.

2,365 citations


Journal ArticleDOI
TL;DR: The biophysical and mechanical principles of locomotion at the small scales relevant to cell swimming, tens of micrometers and below are reviewed, with emphasis on the simple physical picture and fundamental flow physics phenomena in this regime.
Abstract: Cell motility in viscous fluids is ubiquitous and affects many biological processes, including reproduction, infection and the marine life ecosystem. Here we review the biophysical and mechanical principles of locomotion at the small scales relevant to cell swimming, tens of micrometers and below. At this scale, inertia is unimportant and the Reynolds number is small. Our emphasis is on the simple physical picture and fundamental flow physics phenomena in this regime. We first give a brief overview of the mechanisms for swimming motility, and of the basic properties of flows at low Reynolds number, paying special attention to aspects most relevant for swimming such as resistance matrices for solid bodies, flow singularities and kinematic requirements for net translation. Then we review classical theoretical work on cell motility, in particular early calculations of swimming kinematics with prescribed stroke and the application of resistive force theory and slender-body theory to flagellar locomotion. After examining the physical means by which flagella are actuated, we outline areas of active research, including hydrodynamic interactions, biological locomotion in complex fluids, the design of small-scale artificial swimmers and the optimization of locomotion strategies. (Some figures in this article are in colour only in the electronic version) This article was invited by Christoph Schmidt.

2,274 citations


Journal ArticleDOI
TL;DR: Methylation changes in cancer are at sites that vary normally in tissue differentiation, consistent with the epigenetic progenitor model of cancer, which proposes that epigenetic alterations affecting tissue-specific differentiation are the predominant mechanism by which epigenetic changes cause cancer.
Abstract: For the past 25 years, it has been known that alterations in DNA methylation (DNAm) occur in cancer, including hypomethylation of oncogenes and hypermethylation of tumor suppressor genes. However, most studies of cancer methylation have assumed that functionally important DNAm will occur in promoters, and that most DNAm changes in cancer occur in CpG islands. Here we show that most methylation alterations in colon cancer occur not in promoters, and also not in CpG islands, but in sequences up to 2 kb distant, which we term 'CpG island shores'. CpG island shore methylation was strongly related to gene expression, and it was highly conserved in mouse, discriminating tissue types regardless of species of origin. There was a notable overlap (45-65%) of the locations of colon cancer-related methylation changes with those that distinguished normal tissues, with hypermethylation enriched closer to the associated CpG islands, and hypomethylation enriched further from the associated CpG island and resembling that of noncolon normal tissues. Thus, methylation changes in cancer are at sites that vary normally in tissue differentiation, consistent with the epigenetic progenitor model of cancer, which proposes that epigenetic alterations affecting tissue-specific differentiation are the predominant mechanism by which epigenetic changes cause cancer.

2,099 citations


Journal ArticleDOI
TL;DR: In this paper, the authors conduct an empirical assessment of theories concerning risk taking by banks, their ownership structures, and national bank regulations, and show that bank risk taking varies positively with the comparative power of shareholders within the corporate governance structure of each bank.

1,965 citations


Journal ArticleDOI
TL;DR: The Wilkinson Microwave Anisotropy Probe (WMAP) is a medium-class Explorer (MIDEX) satellite aimed at elucidating cosmology through full-sky observations of the cosmic microwave background (CMB) as mentioned in this paper.
Abstract: The Wilkinson Microwave Anisotropy Probe (WMAP) is a Medium-Class Explorer (MIDEX) satellite aimed at elucidating cosmology through full-sky observations of the cosmic microwave background (CMB). The WMAP full-sky maps of the temperature and polarization anisotropy in five frequency bands provide our most accurate view to date of conditions in the early universe. The multi-frequency data facilitate the separation of the CMB signal from foreground emission arising both from our Galaxy and from extragalactic sources. The CMB angular power spectrum derived from these maps exhibits a highly coherent acoustic peak structure which makes it possible to extract a wealth of information about the composition and history of the universe. as well as the processes that seeded the fluctuations. WMAP data have played a key role in establishing ACDM as the new standard model of cosmology (Bennett et al. 2003: Spergel et al. 2003; Hinshaw et al. 2007: Spergel et al. 2007): a flat universe dominated by dark energy, supplemented by dark matter and atoms with density fluctuations seeded by a Gaussian, adiabatic, nearly scale invariant process. The basic properties of this universe are determined by five numbers: the density of matter, the density of atoms. the age of the universe (or equivalently, the Hubble constant today), the amplitude of the initial fluctuations, and their scale dependence. By accurately measuring the first few peaks in the angular power spectrum, WMAP data have enabled the following accomplishments: Showing the dark matter must be non-baryonic and interact only weakly with atoms and radiation. The WMAP measurement of the dark matter density puts important constraints on supersymmetric dark matter models and on the properties of other dark matter candidates. With five years of data and a better determination of our beam response, this measurement has been significantly improved. Precise determination of the density of atoms in the universe. The agreement between the atomic density derived from WMAP and the density inferred from the deuterium abundance is an important test of the standard big bang model. Determination of the acoustic scale at redshift z = 1090. Similarly, the recent measurement of baryon acoustic oscillations (BAO) in the galaxy power spectrum (Eisenstein et al. 2005) has determined the acoustic scale at redshift z approx. 0.35. When combined, these standard rulers accurately measure the geometry of the universe and the properties of the dark energy. These data require a nearly flat universe dominated by dark energy consistent with a cosmological constant. Precise determination of the Hubble Constant, in conjunction with BAO observations. Even when allowing curvature (Omega(sub 0) does not equal 1) and a free dark energy equation of state (w does not equal -1), the acoustic data determine the Hubble constant to within 3%. The measured value is in excellent agreement with independent results from the Hubble Key Project (Freedman et al. 2001), providing yet another important consistency test for the standard model. Significant constraint of the basic properties of the primordial fluctuations. The anti-correlation seen in the temperature/polarization (TE) correlation spectrum on 4deg scales implies that the fluctuations are primarily adiabatic and rule out defect models and isocurvature models as the primary source of fluctuations (Peiris et al. 2003).

1,870 citations


Journal ArticleDOI
TL;DR: In this paper, the authors present cosmological constraints from the Wilkinson Microwave Anisotropy Probe (WMAP) alone for both the ACDM model and a set of possible extensions.
Abstract: The Wilkinson Microwave Anisotropy Probe (WMAP), launched in 2001, has mapped out the Cosmic Microwave Background with unprecedented accuracy over the whole sky. Its observations have led to the establishment of a simple concordance cosmological model for the contents and evolution of the universe, consistent with virtually all other astronomical measurements. The WMAP first-year and three-year data have allowed us to place strong constraints on the parameters describing the ACDM model. a flat universe filled with baryons, cold dark matter, neutrinos. and a cosmological constant. with initial fluctuations described by nearly scale-invariant power law fluctuations, as well as placing limits on extensions to this simple model (Spergel et al. 2003. 2007). With all-sky measurements of the polarization anisotropy (Kogut et al. 2003; Page et al. 2007), two orders of magnitude smaller than the intensity fluctuations. WMAP has not only given us an additional picture of the universe as it transitioned from ionized to neutral at redshift z approx.1100. but also an observation of the later reionization of the universe by the first stars. In this paper we present cosmological constraints from WMAP alone. for both the ACDM model and a set of possible extensions. We also consider tlle consistency of WMAP constraints with other recent astronomical observations. This is one of seven five-year WMAP papers. Hinshaw et al. (2008) describe the data processing and basic results. Hill et al. (2008) present new beam models arid window functions, Gold et al. (2008) describe the emission from Galactic foregrounds, and Wright et al. (2008) the emission from extra-Galactic point sources. The angular power spectra are described in Nolta et al. (2008), and Komatsu et al. (2008) present and interpret cosmological constraints based on combining WMAP with other data. WMAP observations are used to produce full-sky maps of the CMB in five frequency bands centered at 23, 33, 41, 61, and 94 GHz (Hinshaw et al. 2008). With five years of data, we are now able to place better limits on the ACDM model. as well as to move beyond it to test the composition of the universe. details of reionization. sub-dominant components, characteristics of inflation, and primordial fluctuations. We have more than doubled the amount of polarized data used for cosmological analysis. allowing a better measure of the large-scale E-mode signal (Nolta et al. 2008). To this end we describe an alternative way to remove Galactic foregrounds from low resolution polarization maps in which Galactic emission is marginalized over, providing a cross-check of our results. With longer integration we also better probe the second and third acoustic peaks in the temperature angular power spectrum, and have many more year-to-year difference maps available for cross-checking systematic effects (Hinshaw et al. 2008).

1,600 citations


Journal ArticleDOI
TL;DR: Treatment of mild gestational diabetes mellitus did not significantly reduce the frequency of a composite outcome that included stillbirth or perinatal death and several neonatal complications, but it did reduce the risks of fetal overgrowth, shoulder dystocia, cesarean delivery, and hypertensive disorders.
Abstract: Background It is uncertain whether treatment of mild gestational diabetes mellitus improves pregnancy outcomes. Methods Women who were in the 24th to 31st week of gestation and who met the criteria for mild gestational diabetes mellitus (i.e., an abnormal result on an oral glucose-tolerance test but a fasting glucose level below 95 mg per deciliter [5.3 mmol per liter]) were randomly assigned to usual prenatal care (control group) or dietary intervention, self-monitoring of blood glucose, and insulin therapy, if necessary (treatment group). The primary outcome was a composite of stillbirth or perinatal death and neonatal complications, including hyperbilirubinemia, hypoglycemia, hyperinsulinemia, and birth trauma. Results A total of 958 women were randomly assigned to a study group — 485 to the treatment group and 473 to the control group. We observed no significant difference between groups in the frequency of the composite outcome (32.4% and 37.0% in the treatment and control groups, respectively; P=0.1...

1,587 citations


Proceedings ArticleDOI
04 Nov 2009
TL;DR: In this paper, the authors evaluate datapath validation and adaptive beaconing in CTP Noe, a sensor network tree collection protocol, on both interference-free and interference-prone channels.
Abstract: This paper presents and evaluates two principles for wireless routing protocols. The first is datapath validation: data traffic quickly discovers and fixes routing inconsistencies. The second is adaptive beaconing: extending the Trickle algorithm to routing control traffic reduces route repair latency and sends fewer beacons.We evaluate datapath validation and adaptive beaconing in CTP Noe, a sensor network tree collection protocol. We use 12 different testbeds ranging in size from 20--310 nodes, comprising seven platforms, and six different link layers, on both interference-free and interference-prone channels. In all cases, CTP Noe delivers > 90% of packets. Many experiments achieve 99.9%. Compared to standard beaconing, CTP Noe sends 73% fewer beacons while reducing topology repair latency by 99.8%. Finally, when using low-power link layers, CTP Noe has duty cycles of 3% while supporting aggregate loads of 30 packets/minute.

1,516 citations


Posted Content
TL;DR: A statistical framework is developed that uses satellite data on lights growth to augment existing income growth measures, under the assumption that measurement error in using observed light as an indicator of income is uncorrelated with measurementerror in national income accounts.
Abstract: GDP growth is often measured poorly for countries and rarely measured at all for cities or subnational regions. We propose a readily available proxy: satellite data on lights at night. We develop a statistical framework that uses lights growth to augment existing income growth measures, under the assumption that measurement error in using observed light as an indicator of income is uncorrelated with measurement error in national income accounts. For countries with good national income accounts data, information on growth of lights is of marginal value in estimating the true growth rate of income, while for countries with the worst national income accounts, the optimal estimate of true income growth is a composite with roughly equal weights. Among poor-data countries, our new estimate of average annual growth differs by as much as 3 percentage points from official data. Lights data also allow for measurement of income growth in sub- and supranational regions. As an application, we examine growth in Sub Saharan African regions over the last 17 years. We find that real incomes in non-coastal areas have grown faster by 1/3 of an annual percentage point than coastal areas; non-malarial areas have grown faster than malarial ones by 1/3 to 2/3 annual percent points; and primate city regions have grown no faster than hinterland areas. Such applications point toward a research program in which "empirical growth" need no longer be synonymous with "national income accounts."

Journal ArticleDOI
TL;DR: Patients with health care proxies who have an understanding of the prognosis and clinical course are likely to receive less aggressive care near the end of life, and these complications are associated with high 6-month mortality rates.
Abstract: BACKGROUND Dementia is a leading cause of death in the United States but is underrecognized as a terminal illness. The clinical course of nursing home residents with advanced dementia has not been well described. METHODS We followed 323 nursing home residents with advanced dementia and their health care proxies for 18 months in 22 nursing homes. Data were collected to characterize the residents' survival, clinical complications, symptoms, and treatments and to determine the proxies' understanding of the residents' prognosis and the clinical complications expected in patients with advanced dementia. RESULTS Over a period of 18 months, 54.8% of the residents died. The probability of pneumonia was 41.1%; a febrile episode, 52.6%; and an eating problem, 85.8%. After adjustment for age, sex, and disease duration, the 6-month mortality rate for residents who had pneumonia was 46.7%; a febrile episode, 44.5%; and an eating problem, 38.6%. Distressing symptoms, including dyspnea (46.0%) and pain (39.1%), were common. In the last 3 months of life, 40.7% of residents underwent at least one burdensome intervention (hospitalization, emergency room visit, parenteral therapy, or tube feeding). Residents whose proxies had an understanding of the poor prognosis and clinical complications expected in advanced dementia were much less likely to have burdensome interventions in the last 3 months of life than were residents whose proxies did not have this understanding (adjusted odds ratio, 0.12; 95% confidence interval, 0.04 to 0.37). CONCLUSIONS Pneumonia, febrile episodes, and eating problems are frequent complications in patients with advanced dementia, and these complications are associated with high 6-month mortality rates. Distressing symptoms and burdensome interventions are also common among such patients. Patients with health care proxies who have an understanding of the prognosis and clinical course are likely to receive less aggressive care near the end of life.

Proceedings ArticleDOI
29 Jun 2009
TL;DR: A benchmark consisting of a collection of tasks that are run on an open source version of MR as well as on two parallel DBMSs shows a dramatic performance difference between the two paradigms.
Abstract: There is currently considerable enthusiasm around the MapReduce (MR) paradigm for large-scale data analysis [17]. Although the basic control flow of this framework has existed in parallel SQL database management systems (DBMS) for over 20 years, some have called MR a dramatically new computing model [8, 17]. In this paper, we describe and compare both paradigms. Furthermore, we evaluate both kinds of systems in terms of performance and development complexity. To this end, we define a benchmark consisting of a collection of tasks that we have run on an open source version of MR as well as on two parallel DBMSs. For each task, we measure each system's performance for various degrees of parallelism on a cluster of 100 nodes. Our results reveal some interesting trade-offs. Although the process to load data into and tune the execution of parallel DBMSs took much longer than the MR system, the observed performance of these DBMSs was strikingly better. We speculate about the causes of the dramatic performance difference and consider implementation concepts that future systems should take from both kinds of architectures.

Journal ArticleDOI
TL;DR: This tutorial review summarizes the recent advances in the chemical synthesis and potential applications of monodisperse magnetic nanoparticles and outlines the surface, structural, and magnetic properties of these nanoparticles for biomedicine and magnetic energy storage applications.
Abstract: This tutorial review summarizes the recent advances in the chemical synthesis and potential applications of monodisperse magnetic nanoparticles. After a brief introduction to nanomagnetism, the review focuses on recent developments in solution phase syntheses of monodisperse MFe2O4, Co, Fe, CoFe, FePt and SmCo5 nanoparticles. The review further outlines the surface, structural, and magnetic properties of these nanoparticles for biomedicine and magnetic energy storage applications.

Journal ArticleDOI
TL;DR: This work provides novel insight into the role of aging and the environment in susceptibility to diseases such as cancer and critically informs the field of epigenomics by providing evidence of epigenetic dysregulation by age-related methylation alterations.
Abstract: Epigenetic control of gene transcription is critical for normal human development and cellular differentiation. While alterations of epigenetic marks such as DNA methylation have been linked to cancers and many other human diseases, interindividual epigenetic variations in normal tissues due to aging, environmental factors, or innate susceptibility are poorly characterized. The plasticity, tissue-specific nature, and variability of gene expression are related to epigenomic states that vary across individuals. Thus, population-based investigations are needed to further our understanding of the fundamental dynamics of normal individual epigenomes. We analyzed 217 non-pathologic human tissues from 10 anatomic sites at 1,413 autosomal CpG loci associated with 773 genes to investigate tissue-specific differences in DNA methylation and to discern how aging and exposures contribute to normal variation in methylation. Methylation profile classes derived from unsupervised modeling were significantly associated with age (P<0.0001) and were significant predictors of tissue origin (P<0.0001). In solid tissues (n = 119) we found striking, highly significant CpG island-dependent correlations between age and methylation; loci in CpG islands gained methylation with age, loci not in CpG islands lost methylation with age (P<0.001), and this pattern was consistent across tissues and in an analysis of blood-derived DNA. Our data clearly demonstrate age- and exposure-related differences in tissue-specific methylation and significant age-associated methylation patterns which are CpG island context-dependent. This work provides novel insight into the role of aging and the environment in susceptibility to diseases such as cancer and critically informs the field of epigenomics by providing evidence of epigenetic dysregulation by age-related methylation alterations. Collectively we reveal key issues to consider both in the construction of reference and disease-related epigenomes and in the interpretation of potentially pathologically important alterations.

Journal ArticleDOI
TL;DR: The promise of nanomaterials for bone, cartilage, vascular, neural and bladder tissue engineering applications will be reviewed and as an important future area of research, the potential risk and toxicity ofnanomaterial synthesis and use related to human health are emphasized.

Journal ArticleDOI
01 Aug 2009
TL;DR: This paper explores the feasibility of building a hybrid system that takes the best features from both technologies; the prototype built approaches parallel databases in performance and efficiency, yet still yields the scalability, fault tolerance, and flexibility of MapReduce-based systems.
Abstract: The production environment for analytical data management applications is rapidly changing. Many enterprises are shifting away from deploying their analytical databases on high-end proprietary machines, and moving towards cheaper, lower-end, commodity hardware, typically arranged in a shared-nothing MPP architecture, often in a virtualized environment inside public or private "clouds". At the same time, the amount of data that needs to be analyzed is exploding, requiring hundreds to thousands of machines to work in parallel to perform the analysis.There tend to be two schools of thought regarding what technology to use for data analysis in such an environment. Proponents of parallel databases argue that the strong emphasis on performance and efficiency of parallel databases makes them well-suited to perform such analysis. On the other hand, others argue that MapReduce-based systems are better suited due to their superior scalability, fault tolerance, and flexibility to handle unstructured data. In this paper, we explore the feasibility of building a hybrid system that takes the best features from both technologies; the prototype we built approaches parallel databases in performance and efficiency, yet still yields the scalability, fault tolerance, and flexibility of MapReduce-based systems.

Journal ArticleDOI
06 Mar 2009-PLOS ONE
TL;DR: This paper follows the same procedures described previously to develop an updated list of SDRMs that are likely to be useful for ongoing and future studies of transmitted drug resistance and concludes that the updated SDRM list has 93 mutations.
Abstract: Programs that monitor local, national, and regional levels of transmitted HIV-1 drug resistance inform treatment guidelines and provide feedback on the success of HIV-1 treatment and prevention programs. To accurately compare transmitted drug resistance rates across geographic regions and times, the World Health Organization has recommended the adoption of a consensus genotypic definition of transmitted HIV-1 drug resistance. In January 2007, we outlined criteria for developing a list of mutations for drug-resistance surveillance and compiled a list of 80 RT and protease mutations meeting these criteria (surveillance drug resistance mutations; SDRMs). Since January 2007, several new drugs have been approved and several new drug-resistance mutations have been identified. In this paper, we follow the same procedures described previously to develop an updated list of SDRMs that are likely to be useful for ongoing and future studies of transmitted drug resistance. The updated SDRM list has 93 mutations including 34 NRTI-resistance mutations at 15 RT positions, 19 NNRTI-resistance mutations at 10 RT positions, and 40 PI-resistance mutations at 18 protease positions.

Journal ArticleDOI
TL;DR: It is confirmed that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk, however, a substantial proportion of head and head cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head andneck cancer among women and among young-onset cases.
Abstract: Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter ( ψ ) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk ( ψ = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases 60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases. (Cancer Epidemiol Biomarkers Prev 2009;18(2):541–50)

Proceedings ArticleDOI
09 Nov 2009
TL;DR: In this article, the authors present a definitional framework and efficient constructions for dynamic provable data possession (DPDP), which extends the PDP model to support provable updates to stored data.
Abstract: We consider the problem of efficiently proving the integrity of data stored at untrusted servers. In the provable data possession (PDP) model, the client preprocesses the data and then sends it to an untrusted server for storage, while keeping a small amount of meta-data. The client later asks the server to prove that the stored data has not been tampered with or deleted (without downloading the actual data). However, the original PDP scheme applies only to static (or append-only) files.We present a definitional framework and efficient constructions for dynamic provable data possession (DPDP), which extends the PDP model to support provable updates to stored data. We use a new version of authenticated dictionaries based on rank information. The price of dynamic updates is a performance change from O(1) to O(logn) (or O(nelog n), for a file consisting of n blocks, while maintaining the same (or better, respectively) probability of misbehavior detection. Our experiments show that this slowdown is very low in practice (e.g. 415KB proof size and 30ms computational overhead for a 1GB file). We also show how to apply our DPDP scheme to outsourced file systems and version control systems (e.g. CVS).

Journal ArticleDOI
TL;DR: The approach provides a practical method for learning high-order Markov random field models with potential functions that extend over large pixel neighborhoods with non-linear functions of many linear filter responses.
Abstract: We develop a framework for learning generic, expressive image priors that capture the statistics of natural scenes and can be used for a variety of machine vision tasks. The approach provides a practical method for learning high-order Markov random field (MRF) models with potential functions that extend over large pixel neighborhoods. These clique potentials are modeled using the Product-of-Experts framework that uses non-linear functions of many linear filter responses. In contrast to previous MRF approaches all parameters, including the linear filters themselves, are learned from training data. We demonstrate the capabilities of this Field-of-Experts model with two example applications, image denoising and image inpainting, which are implemented using a simple, approximate inference scheme. While the model is trained on a generic image database and is not tuned toward a specific application, we obtain results that compete with specialized techniques.

Journal ArticleDOI
TL;DR: This Review surveys anatomical, neuroimaging, electrophysiological and developmental findings, and considers the question: could the organization of the frontal cortex be hierarchical?
Abstract: The frontal lobes in the brain are a component of the cerebral system that supports goal-directed behaviour. However, their functional organization remains controversial. Recent studies have reported rostro-caudal distinctions in frontal cortex activity based on the abstractness of action representations. In addition, some have proposed that these differences reflect a hierarchical organization, whereby anterior frontal regions influence processing by posterior frontal regions during the realization of abstract action goals as motor acts. However, few have considered whether the anatomy and physiology of the frontal lobes support such a scheme. To address this gap, this Review surveys anatomical, neuroimaging, electrophysiological and developmental findings, and considers the question: could the organization of the frontal cortex be hierarchical?

Journal ArticleDOI
TL;DR: Questions remain about which groups of patients benefit from therapy and at which point in the course of disease this therapy should be initiated, and limited rigorous evidence exists demonstrating the effect of these therapies on important long-term clinical outcomes.
Abstract: National Institutes of Health (NIH) consensus and stateof-the-science statements are prepared by independent panels of health professionals and public representatives on the basis of 1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality (AHRQ); 2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session; 3) questions and statements from conference attendees during open discussion periods that are part of the public session; and 4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the U.S. government. The statement reflects the panel’s assessment of medical knowledge available at the time the statement was written. Thus, it provides a “snapshot in time” of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research. Hepatitis B is a major cause of liver disease worldwide, ranking as a substantial cause of cirrhosis and hepatocellular carcinoma. The development and use of a vaccine for hepatitis B virus (HBV) has resulted in a substantial decline in the number of new cases of acute hepatitis B among children, adolescents, and adults in the United States. However, this success has not yet been duplicated worldwide, and both acute and chronic HBV infection continue to represent important global health problems. Seven treatments are currently approved for adult patients with chronic HBV infection in the United States: interferon-, pegylated interferon-, lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate. Interferon- and lamivudine have been approved for children with HBV infection. Although available randomized, controlled trials (RCTs) show encouraging short-term results— demonstrating the favorable effect of these agents on such intermediate markers of disease as HBV DNA level, liver enzyme tests, and liver histology— limited rigorous evidence exists demonstrating the effect of these therapies on important long-term clinical outcomes, such as the development of hepatocellular carcinoma or a reduction in deaths. Questions therefore remain about which groups of patients benefit from therapy and at which point in the course of disease this therapy should be initiated.


Journal ArticleDOI
TL;DR: It is concluded that the best way to protect salt marshes and the services they provide is through the integrated approach of ecosystem-based management.
Abstract: Salt marshes are among the most abundant, fertile, and accessible coastal habitats on earth, and they provide more ecosystem services to coastal populations than any other environment. Since the Middle Ages, humans have manipulated salt marshes at a grand scale, altering species composition, distribution, and ecosystem function. Here, we review historic and contemporary human activities in marsh ecosystems—exploitation of plant products; conversion to farmland, salt works, and urban land; introduction of non-native species; alteration of coastal hydrology; and metal and nutrient pollution. Unexpectedly, diverse types of impacts can have a similar consequence, turning salt marsh food webs upside down, dramatically increasing top down control. Of the various impacts, invasive species, runaway consumer effects, and sea level rise represent the greatest threats to salt marsh ecosystems. We conclude that the best way to protect salt marshes and the services they provide is through the integrated approach of ecosystem-based management.

Journal ArticleDOI
TL;DR: An algorithm utilizing HE4 and CA125 successfully classified patients into high and low risk groups with 93.8% of EOC correctly classified as high risk, which can be used to effectively triage patients to centers of excellence.

Journal ArticleDOI
TL;DR: New sequence data and methods strongly uphold previous suggestions that Acoelomorpha is sister clade to all other bilaterian animals, find diminishing evidence for the placement of the enigmatic Xenoturbella within Deuterostomia, and place Cycliophora with Entoprocta and EctoproCTa.
Abstract: A clear picture of animal relationships is a prerequisite to understand how the morphological and ecological diversity of animals evolved over time. Among others, the placement of the acoelomorph flatworms, Acoela and Nemertodermatida, has fundamental implications for the origin and evolution of various animal organ systems. Their position, however, has been inconsistent in phylogenetic studies using one or several genes. Furthermore, Acoela has been among the least stable taxa in recent animal phylogenomic analyses, which simultaneously examine many genes from many species, while Nemertodermatida has not been sampled in any phylogenomic study. New sequence data are presented here from organisms targeted for their instability or lack of representation in prior analyses, and are analysed in combination with other publicly available data. We also designed new automated explicit methods for identifying and selecting common genes across different species, and developed highly optimized supercomputing tools to reconstruct relationships from gene sequences. The results of the work corroborate several recently established findings about animal relationships and provide new support for the placement of other groups. These new data and methods strongly uphold previous suggestions that Acoelomorpha is sister clade to all other bilaterian animals, find diminishing evidence for the placement of the enigmatic Xenoturbella within Deuterostomia, and place Cycliophora with Entoprocta and Ectoprocta. The work highlights the implications that these arrangements have for metazoan evolution and permits a clearer picture of ancestral morphologies and life histories in the deep past.

Journal ArticleDOI
TL;DR: Elective repeat cesarean delivery before 39 weeks of gestation is common and is associated with respiratory and other adverse neonatal outcomes.
Abstract: BACKGROUND Because of increased rates of respiratory complications, elective cesarean delivery is discouraged before 39 weeks of gestation unless there is evidence of fetal lung maturity. We assessed associations between elective cesarean delivery at term (37 weeks of gestation or longer) but before 39 weeks of gestation and neonatal outcomes. METHODS We studied a cohort of consecutive patients undergoing repeat cesarean sections performed at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network from 1999 through 2002. Women with viable singleton pregnancies delivered electively (i.e., before the onset of labor and without any recognized indications for delivery before 39 weeks of gestation) were included. The primary outcome was the composite of neonatal death and any of several adverse events, including respiratory complications, treated hypoglycemia, newborn sepsis, and admission to the neonatal intensive care unit (ICU). RESULTS Of 24,077 repeat cesarean deliveries at term, 13,258 were performed electively; of these, 35.8% were performed before 39 completed weeks of gestation (6.3% at 37 weeks and 29.5% at 38 weeks) and 49.1% at 39 weeks of gestation. One neonatal death occurred. As compared with births at 39 weeks, births at 37 weeks and at 38 weeks were associated with an increased risk of the primary outcome (adjusted odds ratio for births at 37 weeks, 2.1; 95% confidence interval [CI], 1.7 to 2.5; adjusted odds ratio for births at 38 weeks, 1.5; 95% CI, 1.3 to 1.7; P for trend <0.001). The rates of adverse respiratory outcomes, mechanical ventilation, newborn sepsis, hypoglycemia, admission to the neonatal ICU, and hospitalization for 5 days or more were increased by a factor of 1.8 to 4.2 for births at 37 weeks and 1.3 to 2.1 for births at 38 weeks. CONCLUSIONS Elective repeat cesarean delivery before 39 weeks of gestation is common and is associated with respiratory and other adverse neonatal outcomes.

Journal ArticleDOI
TL;DR: In this paper, the authors suggest that inequality in the distribution of landownership adversely affected the emergence of human-capital promoting institutions (e.g. public schooling), and thus the pace and the nature of the transition from an agricultural to an industrial economy, contributing to the divergence in income per capita across countries.
Abstract: This paper suggests that inequality in the distribution of landownership adversely affected the emergence of human-capital promoting institutions (e.g. public schooling), and thus the pace and the nature of the transition from an agricultural to an industrial economy, contributing to the emergence of the great divergence in income per capita across countries. The prediction of the theory regarding the adverse effect of the concentration of landownership on education expenditure is established empirically based on evidence from the beginning of the 20th century in the U.S.

Journal ArticleDOI
TL;DR: Versatility of the genome of pneumococci and the bacteria's polygenic virulence capabilities show that a multifaceted approach with many vaccine antigens, antibiotic combinations, and immunoadjuvant therapies will be needed to control this microbe.