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Showing papers by "Rutgers University published in 2006"


Journal ArticleDOI
TL;DR: Genalex is a user-friendly cross-platform package that runs within Microsoft Excel, enabling population genetic analyses of codominant, haploid and binary data.
Abstract: genalex is a user-friendly cross-platform package that runs within Microsoft Excel, enabling population genetic analyses of codominant, haploid and binary data. Allele frequency-based analyses include heterozygosity, F statistics, Nei's genetic distance, population assignment, probabilities of identity and pairwise relatedness. Distance-based calculations include amova, principal coordinates analysis (PCA), Mantel tests, multivariate and 2D spatial autocorrelation and twogener. More than 20 different graphs summarize data and aid exploration. Sequence and genotype data can be imported from automated sequencers, and exported to other software. Initially designed as tool for teaching, genalex 6 now offers features for researchers as well. Documentation and the program are available at http://www.anu.edu.au/BoZo/GenAlEx/

15,786 citations


Journal ArticleDOI
TL;DR: This work examines less structured interview strategies in which the person interviewed is more a participant in meaning making than a conduit from which information is retrieved.
Abstract: BACKGROUND Interviews are among the most familiar strategies for collecting qualitative data. The different qualitative interviewing strategies in common use emerged from diverse disciplinary perspectives resulting in a wide variation among interviewing approaches. Unlike the highly structured survey interviews and questionnaires used in epidemiology and most health services research, we examine less structured interview strategies in which the person interviewed is more a participant in meaning making than a conduit from which information is retrieved. PURPOSE In this article we briefly review the more common qualitative interview methods and then focus on the widely used individual face-to-face in-depth interview, which seeks to foster learning about individual experiences and perspectives on a given set of issues. We discuss methods for conducting in-depth interviews and consider relevant ethical issues with particular regard to the rights and protection of the participants.

4,956 citations


Book
01 Jan 2006
TL;DR: The brain's default state: self-organized oscillations in rest and sleep, and perturbation of the default patterns by experience.
Abstract: Prelude. Cycle 1. Introduction. Cycle 2. Structure defines function. Cycle 3. Diversity of cortical functions is provided by inhibition. Cycle 4. Windows on the brain. Cycle 5. A system of rhythms: from simple to complex dynamics. Cycle 6. Synchronization by oscillation. Cycle 7. The brain's default state: self-organized oscillations in rest and sleep. Cycle 8. Perturbation of the default patterns by experience. Cycle 9. The gamma buzz: gluing by oscillations in the waking brain. Cycle 10. Perceptions and actions are brain state-dependent. Cycle 11. Oscillations in the "other cortex:" navigation in real and memory space. Cycle 12. Coupling of systems by oscillations. Cycle 13. The tough problem. References.

4,266 citations


Journal ArticleDOI
TL;DR: This protocol details the basic steps of obtaining and interpreting CD data, and methods for analyzing spectra to estimate the secondary structural composition of proteins.
Abstract: Circular dichroism (CD) is an excellent tool for rapid determination of the secondary structure and folding properties of proteins that have been obtained using recombinant techniques or purified from tissues. The most widely used applications of protein CD are to determine whether an expressed, purified protein is folded, or if a mutation affects its conformation or stability. In addition, it can be used to study protein interactions. This protocol details the basic steps of obtaining and interpreting CD data, and methods for analyzing spectra to estimate the secondary structural composition of proteins. CD has the advantage that measurements may be made on multiple samples containing < or =20 microg of proteins in physiological buffers in a few hours. However, it does not give the residue-specific information that can be obtained by x-ray crystallography or NMR.

3,093 citations


Journal ArticleDOI
TL;DR: An overview and tutorial is presented describing genetic algorithms (GA) developed specifically for problems with multiple objectives that differ primarily from traditional GA by using specialized fitness functions and introducing methods to promote solution diversity.

2,943 citations


Journal ArticleDOI
TL;DR: Current evidence confirms that, as proposed by the Baas-Becking hypothesis, 'the environment selects' and is, in part, responsible for spatial variation in microbial diversity, but recent studies also dispute the idea that 'everything is everywhere'.
Abstract: We review the biogeography of microorganisms in light of the biogeography of macroorganisms A large body of research supports the idea that free-living microbial taxa exhibit biogeographic patterns Current evidence confirms that, as proposed by the Baas-Becking hypothesis, 'the environment selects' and is, in part, responsible for spatial variation in microbial diversity However, recent studies also dispute the idea that 'everything is everywhere' We also consider how the processes that generate and maintain biogeographic patterns in macroorganisms could operate in the microbial world

2,456 citations


Journal ArticleDOI
07 Dec 2006-Nature
TL;DR: Global ocean NPP changes detected from space over the past decade are described, dominated by an initial increase in NPP of 1,930 teragrams of carbon a year, followed by a prolonged decrease averaging 190 Tg C yr-1.
Abstract: Contributing roughly half of the biosphere's net primary production (NPP), photosynthesis by oceanic phytoplankton is a vital link in the cycling of carbon between living and inorganic stocks. Each day, more than a hundred million tons of carbon in the form of CO2 are fixed into organic material by these ubiquitous, microscopic plants of the upper ocean, and each day a similar amount of organic carbon is transferred into marine ecosystems by sinking and grazing. The distribution of phytoplankton biomass and NPP is defined by the availability of light and nutrients (nitrogen, phosphate, iron). These growth-limiting factors are in turn regulated by physical processes of ocean circulation, mixed-layer dynamics, upwelling, atmospheric dust deposition, and the solar cycle. Satellite measurements of ocean colour provide a means of quantifying ocean productivity on a global scale and linking its variability to environmental factors. Here we describe global ocean NPP changes detected from space over the past decade. The period is dominated by an initial increase in NPP of 1,930 teragrams of carbon a year (Tg C yr(-1)), followed by a prolonged decrease averaging 190 Tg C yr(-1). These trends are driven by changes occurring in the expansive stratified low-latitude oceans and are tightly coupled to coincident climate variability. This link between the physical environment and ocean biology functions through changes in upper-ocean temperature and stratification, which influence the availability of nutrients for phytoplankton growth. The observed reductions in ocean productivity during the recent post-1999 warming period provide insight on how future climate change can alter marine food webs.

1,954 citations


Journal ArticleDOI
TL;DR: In this article, a review of the basic ideas and techniques of spectral density functional theory which are currently used in electronic structure calculations of strongly correlated materials where the one-dimensional electron description breaks down is presented.
Abstract: We present a review of the basic ideas and techniques of the spectral density functional theory which are currently used in electronic structure calculations of strongly{correlated materials where the one{electron description breaks down. We illustrate the method with several examples where interactions play a dominant role: systems near metal{insulator transition, systems near volume collapse transition, and systems with local moments.

1,921 citations


Journal ArticleDOI
TL;DR: Limiting autophagy under conditions of nutrient limitation can restore cell death to apoptosis-refractory tumors, but this necrosis is associated with inflammation and accelerated tumor growth.

1,888 citations


Journal ArticleDOI
TL;DR: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones.
Abstract: Background The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. Methods We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. Results Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with...

1,765 citations


Journal ArticleDOI
TL;DR: In this paper, the formulation and simulation characteristics of two new global coupled climate models developed at NOAA's Geophysical Fluid Dynamics Laboratory (GFDL) are described and two versions of the coupled model are described.
Abstract: The formulation and simulation characteristics of two new global coupled climate models developed at NOAA's Geophysical Fluid Dynamics Laboratory (GFDL) are described. The models were designed to simulate atmospheric and oceanic climate and variability from the diurnal time scale through multicentury climate change, given our computational constraints. In particular, an important goal was to use the same model for both experimental seasonal to interannual forecasting and the study of multicentury global climate change, and this goal has been achieved. Two versions of the coupled model are described, called CM2.0 and CM2.1. The versions differ primarily in the dynamical core used in the atmospheric component, along with the cloud tuning and some details of the land and ocean components. For both coupled models, the resolution of the land and atmospheric components is 2° latitude × 2.5° longitude; the atmospheric model has 24 vertical levels. The ocean resolution is 1° in latitude and longitude, wi...

Journal ArticleDOI
07 Apr 2006-Science
TL;DR: Losartan, a drug already in clinical use for hypertension, merits investigation as a therapeutic strategy for patients with Marfan syndrome and has the potential to prevent the major life-threatening manifestation of this disorder.
Abstract: Aortic aneurysm and dissection are manifestations of Marfan syndrome (MFS), a disorder caused by mutations in the gene that encodes fibrillin-1. Selected manifestations of MFS reflect excessive signaling by the transforming growth factor–β (TGF-β) family of cytokines. We show that aortic aneurysm in a mouse model of MFS is associated with increased TGF-β signaling and can be prevented by TGF-β antagonists such as TGF-β–neutralizing antibody or the angiotensin II type 1 receptor (AT1) blocker, losartan. AT1 antagonism also partially reversed noncardiovascular manifestations of MFS, including impaired alveolar septation. These data suggest that losartan, a drug already in clinical use for hypertension, merits investigation as a therapeutic strategy for patients with MFS and has the potential to prevent the major life-threatening manifestation of this disorder.

Journal ArticleDOI
TL;DR: How studies on joint attention, action observation, task sharing, action coordination and agency contribute to the understanding of the cognitive and neural processes supporting joint action are outlined.

Journal ArticleDOI
TL;DR: It is suggested that terrestrial, freshwater, and marine systems in which denitrification occurs can be organized along a continuum ranging from (1) those in which nitrification and Denitrification are tightly coupled in space and time to (2) thoseIn aquatic ecosystems, N inputs influenceDenitrification rates whereas hydrology and geomorphology influence the proportion of N inputs that are denitrified.
Abstract: Denitrification is a critical process regulating the removal of bioavailable nitrogen (N) from natural and human-altered systems. While it has been extensively studied in terrestrial, freshwater, and marine systems, there has been limited communication among denitrification scientists working in these individual systems. Here, we compare rates of denitrification and controlling factors across a range of ecosystem types. We suggest that terrestrial, freshwater, and marine systems in which denitrification occurs can be organized along a continuum ranging from (1) those in which nitrification and denitrification are tightly coupled in space and time to (2) those in which nitrate production and denitrification are relatively decoupled. In aquatic ecosystems, N inputs influence denitrification rates whereas hydrology and geomorphology influence the proportion of N inputs that are denitrified. Relationships between denitrification and water residence time and N load are remarkably similar across lakes, river reaches, estuaries, and continental shelves. Spatially distributed global models of denitrification suggest that continental shelf sediments account for the largest portion (44%) of total global denitrification, followed by terrestrial soils (22%) and oceanic oxygen minimum zones (OMZs; 14%). Freshwater systems (groundwater, lakes, rivers) account for about 20% and estuaries 1% of total global denitrification. Denitrification of land-based N sources is distributed somewhat differently. Within watersheds, the amount of land-based N denitrified is generally highest in terrestrial soils, with progressively smaller amounts denitrified in groundwater, rivers, lakes and reservoirs, and estuaries. A number of regional exceptions to this general trend of decreasing denitrification in a downstream direction exist, including significant denitrification in continental shelves of N from terrestrial sources. Though terrestrial soils and groundwater are responsible for much denitrification at the watershed scale, per-area denitrification rates in soils and groundwater (kg Nkm � 2 � yr � 1 ) are, on average, approximately one-tenth the per-area rates of denitrification in lakes, rivers, estuaries, continental shelves, or OMZs. A number of potential approaches to increase denitrification on the landscape, and thus decrease N export to sensitive coastal systems exist. However, these have not generally been widely tested for their effectiveness at scales required to significantly reduce N export at the whole watershed scale.

Journal ArticleDOI
TL;DR: Empirical support for Social Information Processing theory in a naturalistic context is provided while offering insight into the complicated way in which ‘‘hon-esty’’ is enacted online.
Abstract: This study investigates self-presentation strategies among online dating participants,exploring how participants manage their online presentation of self in order to accom-plish the goal of finding a romantic partner. Thirty-four individuals active on a largeonline dating site participated in telephone interviews about their online dating experi-ences and perceptions. Qualitative data analysis suggests that participants attended tosmall cues online, mediated the tension between impression management pressures andthe desire to present an authentic sense of self through tactics such as creating a profilethat reflected their ‘‘ideal self,’’ and attempted to establish the veracity of their identityclaims. This study provides empirical support for Social Information Processing theoryin a naturalistic context while offering insight into the complicated way in which ‘‘hon-esty’’ is enacted online.doi:10.1111/j.1083-6101.2006.00020.x

Journal ArticleDOI
06 Oct 2006-Cell
TL;DR: It is reported that SIN1/MIP1 is an essential TORC2/PDK2 subunit for Akt/PKB Ser473 phosphorylation in the hydrophobic motif and that the Sin1-rictor-mTOR function in Akt-Ser473 phosphories is required forTORC2 function in cell survival but is dispensable for TORC1 function.

Journal ArticleDOI
TL;DR: In this article, the authors identify the key challenges facing strategic human resource management (SHRM) going forward and discuss several new directions in both the scholarship and practice of SHRM.

Book ChapterDOI
07 May 2006
TL;DR: A fast method for computation of covariances based on integral images, and the performance of the covariance features is superior to other methods, as it is shown, and large rotations and illumination changes are also absorbed by the covariances matrix.
Abstract: We describe a new region descriptor and apply it to two problems, object detection and texture classification. The covariance of d-features, e.g., the three-dimensional color vector, the norm of first and second derivatives of intensity with respect to x and y, etc., characterizes a region of interest. We describe a fast method for computation of covariances based on integral images. The idea presented here is more general than the image sums or histograms, which were already published before, and with a series of integral images the covariances are obtained by a few arithmetic operations. Covariance matrices do not lie on Euclidean space, therefore we use a distance metric involving generalized eigenvalues which also follows from the Lie group structure of positive definite matrices. Feature matching is a simple nearest neighbor search under the distance metric and performed extremely rapidly using the integral images. The performance of the covariance features is superior to other methods, as it is shown, and large rotations and illumination changes are also absorbed by the covariance matrix.

Journal ArticleDOI
TL;DR: One year of oral cyclophosphamide in patients with symptomatic scleroderma-related interstitial lung disease had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and the health-related quality of life.
Abstract: BACKGROUND We conducted a double-blind, randomized, placebo-controlled trial to determine the effects of oral cyclophosphamide on lung function and health-related symptoms in patients with evidence of active alveolitis and scleroderma-related interstitial lung disease. METHODS At 13 clinical centers throughout the United States, we enrolled 158 patients with scleroderma, restrictive lung physiology, dyspnea, and evidence of inflammatory interstitial lung disease on examination of bronchoalveolar-lavage fluid, thoracic highresolution computed tomography, or both. Patients received oral cyclophosphamide (≤2 mg per kilogram of body weight per day) or matching placebo for one year and were followed for an additional year. Pulmonary function was assessed every three months during the first year, and the primary end point was the forced vital capacity (FVC, expressed as a percentage of the predicted value) at 12 months, after adjustment for the baseline FVC. RESULTS Of 158 patients, 145 completed at least six months of treatment and were included in the analysis. The mean absolute difference in adjusted 12-month FVC percent predicted between the cyclophosphamide and placebo groups was 2.53 percent (95 percent confidence interval, 0.28 to 4.79 percent), favoring cyclophosphamide (P<0.03). There were also treatment-related differences in physiological and symptom outcomes, and the difference in FVC was maintained at 24 months. There was a greater frequency of adverse events in the cyclophosphamide group, but the difference between the two groups in the number of serious adverse events was not significant. CONCLUSIONS One year of oral cyclophosphamide in patients with symptomatic sclerodermarelated interstitial lung disease had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and the health-related quality of life. The effects on lung function were maintained through the 24 months of the study.

Journal ArticleDOI
TL;DR: In this paper, the authors examined the effects of environmental, organizational and top managers' characteristics on the initiation, adoption decision and implementation of innovation and found that while each dimension accounts for unique variance in the adoption of innovation, organizational characteristics and attitudes toward innovation have a stronger influence than environmental and top manager's demographic characteristics.
Abstract: Multidimensional empirical examinations of the adoption of innovations in organizations, and the influence of factors within each dimension on the phases of adoption, are scarce. This study examines the effects of environmental, organizational and top managers' characteristics on the initiation, adoption decision and implementation of innovation. Using a sample of approximately 1200 public organizations in the United States, we found that while each dimension accounts for unique variance in the adoption of innovation, organizational characteristics and top managers' attitudes toward innovation have a stronger influence than environmental and top managers' demographic characteristics. We also found no difference in the direction of effects of any antecedent, but did find differences in the significance of effects of several antecedents, on the phases of innovation adoption. We discuss the implications of these findings and suggest ideas for future research.

Journal ArticleDOI
TL;DR: This article considers network coordination as a means to provide spectrally efficient communications in cellular downlink systems and describes how the antenna outputs are chosen in ways to minimize the out-of-cell interference, and hence to increase the downlink system capacity.
Abstract: In this article we consider network coordination as a means to provide spectrally efficient communications in cellular downlink systems. When network coordination is employed, all base antennas act together as a single network antenna array, and each mobile may receive useful signals from nearby base stations. Furthermore, the antenna outputs are chosen in ways to minimize the out-of-cell interference, and hence to increase the downlink system capacity. When the out-of-cell interference is mitigated, the links can operate in the high signal-to-noise ratio regime. This enables the cellular network to enjoy the great spectral efficiency improvement associated with using multiple antennas

Journal ArticleDOI
TL;DR: Finite element exterior calculus as mentioned in this paper is an approach to the design and understand- ing of finite element discretizations for a wide variety of systems of partial differential equations, which brings to bear tools from differential geometry, algebraic topology, and homological algebra to develop discretiza- tions which are compatible with the geometric, topological and algebraic structures which underlie well-posedness of the PDE problem being solved.
Abstract: Finite element exterior calculus is an approach to the design and understand- ing of finite element discretizations for a wide variety of systems of partial differential equations. This approach brings to bear tools from differential geometry, algebraic topology, and homological algebra to develop discretiza- tions which are compatible with the geometric, topological, and algebraic structures which underlie well-posedness of the PDE problem being solved. In the finite element exterior calculus, many finite element spaces are re- vealed as spaces of piecewise polynomial differential forms. These connect to each other in discrete subcomplexes of elliptic differential complexes, and are also related to the continuous elliptic complex through projections which commute with the complex differential. Applications are made to the finite element discretization of a variety of problems, including the Hodge Lapla- cian, Maxwell's equations, the equations of elasticity, and elliptic eigenvalue problems, and also to preconditioners.

Journal ArticleDOI
TL;DR: In this article, the authors compare observed trajectories to near-future simulations (2010-2029), rather than to the doubled-CO2 or late 21st century conditions that are typically cited.
Abstract: Rises in surface air temperature (SAT) in response to increasing concentrations of greenhouse gases (GHGs) are expected to be amplified in northern high latitudes, with warming most pronounced over the Arctic Ocean owing to the loss of sea ice. Observations document recent warming, but an enhanced Arctic Ocean signal is not readily evident. This disparity, combined with varying model projections of SAT change, and large variability in observed SAT over the 20th century, may lead one to question the concept of Arctic amplification. Disparity is greatly reduced, however, if one compares observed trajectories to near-future simulations (2010–2029), rather than to the doubled-CO2 or late 21st century conditions that are typically cited. These near-future simulations document a preconditioning phase of Arctic amplification, characterized by the initial retreat and thinning of sea ice, with imprints of low-frequency variability. Observations show these same basic features, but with SATs over the Arctic Ocean still largely constrained by the insulating effects of the ice cover and thermal inertia of the upper ocean. Given the general consistency with model projections, we are likely near the threshold when absorption of solar radiation during summer limits ice growth the following autumn and winter, initiating a feedback leading to a substantial increase in Arctic Ocean SATs.

Journal ArticleDOI
TL;DR: The folding structure of the human telomeric sequence in K+ solution determined by NMR demonstrates a novel, unprecedented intramolecular G-quadruplex folding topology with hybrid-type mixed parallel/antiparallel G-strands, and suggests a straightforward pathway for the secondary structure formation with effective packing within the extended human telomersic DNA.
Abstract: Human telomeric DNA consists of tandem repeats of the sequence d(TTAGGG). The formation and stabilization of DNA G-quadruplexes in the human telomeric sequence have been shown to inhibit the activity of telomerase, thus the telomeric DNA G-quadruplex has been considered as an attractive target for cancer therapeutic intervention. However, knowledge of the intact human telomeric G-quadruplex structure(s) formed under physiological conditions is a prerequisite for structure-based rational drug design. Here we report the folding structure of the human telomeric sequence in K+ solution determined by NMR. Our results demonstrate a novel, unprecedented intramolecular G-quadruplex folding topology with hybrid-type mixed parallel/antiparallel G-strands. This telomeric G-quadruplex structure contains three G-tetrads with mixed G-arrangements, which are connected consecutively with a double-chain-reversal side loop and two lateral loops, each consisting of three nucleotides TTA. This intramolecular hybrid-type telomeric G-quadruplex structure formed in K+ solution is distinct from those reported on the 22 nt Tel22 in Na+ solution and in crystalline state in the presence of K+, and appears to be the predominant conformation for the extended 26 nt telomeric sequence Tel26 in the presence of K+, regardless of the presence or absence of Na+. Furthermore, the addition of K+ readily converts the Na+-form conformation to the K+-form hybrid-type G-quadruplex. Our results explain all the reported experimental data on the human telomeric G-quadruplexes formed in the presence of K+, and provide important insights for understanding the polymorphism and interconversion of various G-quadruplex structures formed within the human telomeric sequence, as well as the effects of sequence and cations. This hybrid-type G-quadruplex topology suggests a straightforward pathway for the secondary structure formation with effective packing within the extended human telomeric DNA. The hybrid-type telomeric G-quadruplex is most likely to be of pharmacological relevance, and the distinct folding topology of this G-quadruplex suggests that it can be specifically targeted by G-quadruplex interactive small molecule drugs.

Journal ArticleDOI
08 Feb 2006-JAMA
TL;DR: A dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVDrisk.
Abstract: ContextMultiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed.ObjectiveTo test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk.Design, Setting, and ParticipantsRandomized controlled trial of 48 835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19 541 [40%]) or comparison group (29 294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years.InterventionIntensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials.Main Outcome MeasuresFatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke).ResultsBy year 6, mean fat intake decreased by 8.2% of energy intake in the intervention vs the comparison group, with small decreases in saturated (2.9%), monounsaturated (3.3%), and polyunsaturated (1.5%) fat; increases occurred in intakes of vegetables/fruits (1.1 servings/d) and grains (0.5 serving/d). Low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively; levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention vs comparison groups. The numbers who developed CHD, stroke, and CVD (annualized incidence rates) were 1000 (0.63%), 434 (0.28%), and 1357 (0.86%) in the intervention and 1549 (0.65%), 642 (0.27%), and 2088 (0.88%) in the comparison group. The diet had no significant effects on incidence of CHD (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.06), stroke (HR, 1.02; 95% CI, 0.90-1.15), or CVD (HR, 0.98; 95% CI, 0.92-1.05). Excluding participants with baseline CVD (3.4%), the HRs (95% CIs) for CHD and stroke were 0.94 (0.86-1.02) and 1.02 (0.90-1.17), respectively. Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits.ConclusionsOver a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk.Clinical Trials RegistrationClinicalTrials.gov Identifier: NCT00000611

Journal ArticleDOI
TL;DR: Improvements in fatigue were correlated with decreasing joint pain, whereas improvements in symptoms of depression were less correlated with objective measures of skin clearance or joint pain.

Journal ArticleDOI
TL;DR: Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women, and the long latency associated with the development of colorescopy cancer, along with the seven-year duration of the trial, may have contributed to this null finding.
Abstract: Background Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking. Methods We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women’s Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case–control study. Results The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P = 0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics. Conclusions Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.)

Journal ArticleDOI
TL;DR: In this paper, the authors show deficient induction of interferon-λs by rhinovirus in primary bronchial epithelial cells and alveolar macrophages, which was highly correlated with severity of rhinovirus induced asthma exacerbation and virus load in experimentally infected human volunteers.
Abstract: Rhinoviruses are the major cause of asthma exacerbations, and asthmatics have increased susceptibility to rhinovirus and risk of invasive bacterial infections. Here we show deficient induction of interferon-λs by rhinovirus in asthmatic primary bronchial epithelial cells and alveolar macrophages, which was highly correlated with severity of rhinovirus-induced asthma exacerbation and virus load in experimentally infected human volunteers. Induction by lipopolysaccharide in asthmatic macrophages was also deficient and correlated with exacerbation severity. These results identify previously unknown mechanisms of susceptibility to infection in asthma and suggest new approaches to prevention and/or treatment of asthma exacerbations.

Journal ArticleDOI
TL;DR: In this paper, the authors unpack four characteristics often associated with the term virtuality and argue that each hinders innovation through unique mechanisms, many of which can be overcome by creating a psychologically safe communication climate.
Abstract: To understand why the virtual design strategies that organizations create to foster innovation may in fact hinder it, we unpack four characteristics often associated with the term ‘virtuality’ (geographic dispersion, electronic dependence, structural dynamism, and national diversity) and argue that each hinders innovation through unique mechanisms, many of which can be overcome by creating a psychologically safe communication climate. We first tested the plausibility of our arguments using in-depth qualitative analysis of interviews with 177 members of 14 teams in a variety of industries. A second study constituted a more formal test of hypotheses using survey data collected from 266 members of 56 aerospace design teams. Results show that the four characteristics are not highly intercorrelated, that they have independent and differential effects on innovation, and that a psychologically safe communication climate helps mitigate the challenges they pose. We discuss the implications of these findings for th...

Journal ArticleDOI
TL;DR: In this paper, the authors examined the effect of CEO compensation contracts on misreporting and found that the sensitivity of the option portfolio to stock price is significantly positively related to the propensity to misreport.