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Showing papers by "University of New Mexico published in 2011"


Journal ArticleDOI
TL;DR: In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality.
Abstract: A b s t r ac t Background Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. Methods In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic em - bolism. The trial was designed to test for noninferiority, with key secondary objec - tives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. Results The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the war - farin group (hazard ratio with apixaban, 0.79; 95% confidence interval (CI), 0.66 to 0.95; P<0.001 for noninferiority; P = 0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P = 0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ra - tio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P = 0.42). Conclusions In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb and Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.)

7,154 citations


Journal ArticleDOI
TL;DR: A multivariate analytic approach that optimizes sensitivity and reduces unnecessary testing is introduced and is demonstrated by identifying the effects of age and gender on the resting-state networks of 603 healthy adolescents and adults.
Abstract: As the size of functional and structural MRI datasets expands, it becomes increasingly important to establish a baseline from which diagnostic relevance may be determined, a processing strategy that efficiently prepares data for analysis, and a statistical approach that identifies important effects in a manner that is both robust and reproducible. In this paper, we introduce a multivariate analytic approach that optimizes sensitivity and reduces unnecessary testing. We demonstrate the utility of this mega-analytic approach by identifying the effects of age and gender on the resting-state networks (RSNs) of 603 healthy adolescents and adults (mean age: 23.4 years, range: 12–71 years). Data were collected on the same scanner, preprocessed using an automated analysis pipeline based in SPM, and studied using group independent component analysis. RSNs were identified and evaluated in terms of three primary outcome measures: time course spectral power, spatial map intensity, and functional network connectivity. Results revealed robust effects of age on all three outcome measures, largely indicating decreases in network coherence and connectivity with increasing age. Gender effects were of smaller magnitude but suggested stronger intra-network connectivity in females and more inter-network connectivity in males, particularly with regard to sensorimotor networks. These findings, along with the analysis approach and statistical framework described here, provide a useful baseline for future investigations of brain networks in health and disease.

1,172 citations


Journal ArticleDOI
TL;DR: P porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles are reported that allow a single protocell loaded with a drug cocktail to kill a drug-resistant HCC cell, representing a 106-fold improvement over comparable liposome.
Abstract: Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes.

944 citations


Journal ArticleDOI
TL;DR: In the era of intrapartum chemoprophylaxis to reduce GBS, rates of EO infection have declined but reflect a continued burden of disease, suggesting that Escherichia coli is an important EO pathogen.
Abstract: BACKGROUND: Guidelines for prevention of group B streptococcal (GBS) infection have successfully reduced early onset (EO) GBS disease. Study results suggest that Escherichia coli is an important EO pathogen. OBJECTIVE: To determine EO infection rates, pathogens, morbidity, and mortality in a national network of neonatal centers. METHODS: Infants with EO infection were identified by prospective surveillance at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Network centers. Infection was defined by positive culture results for blood and cerebrospinal fluid obtained from infants aged ≤72 hours plus treatment with antibiotic therapy for ≥5 days. Mother and infant characteristics, treatments, and outcomes were studied. Numbers of cases and total live births (LBs) were used to calculate incidence. RESULTS: Among 396 586 LBs (2006–2009), 389 infants developed EO infection (0.98 cases per 1000 LBs). Infection rates increased with decreasing birth weight. GBS (43%, 0.41 per 1000 LBs) and E coli (29%, 0.28 per 1000 LBs) were most frequently isolated. Most infants with GBS were term (73%); 81% with E coli were preterm. Mothers of 67% of infected term and 58% of infected preterm infants were screened for GBS, and results were positive for 25% of those mothers. Only 76% of mothers with GBS colonization received intrapartum chemoprophylaxis. Although 77% of infected infants required intensive care, 20% of term infants were treated in the normal newborn nursery. Sixteen percent of infected infants died, most commonly with E coli infection (33%). CONCLUSION: In the era of intrapartum chemoprophylaxis to reduce GBS, rates of EO infection have declined but reflect a continued burden of disease. GBS remains the most frequent pathogen in term infants, and E coli the most significant pathogen in preterm infants. Missed opportunities for GBS prevention continue. Prevention of E coli sepsis, especially among preterm infants, remains a challenge.

903 citations


Journal ArticleDOI
TL;DR: This paper uses the cavity method of statistical physics to obtain an asymptotically exact analysis of the phase diagram of the stochastic block model, a commonly used generative model for social and biological networks, and develops a belief propagation algorithm for inferring functional groups or communities from the topology of the network.
Abstract: In this paper we extend our previous work on the stochastic block model, a commonly used generative model for social and biological networks, and the problem of inferring functional groups or communities from the topology of the network. We use the cavity method of statistical physics to obtain an asymptotically exact analysis of the phase diagram. We describe in detail properties of the detectability/undetectability phase transition and the easy/hard phase transition for the community detection problem. Our analysis translates naturally into a belief propagation algorithm for inferring the group memberships of the nodes in an optimal way, i.e., that maximizes the overlap with the underlying group memberships, and learning the underlying parameters of the block model. Finally, we apply the algorithm to two examples of real-world networks and discuss its performance.

897 citations


Journal ArticleDOI
TL;DR: It is suggested that a combination of weight loss and exercise provides greater improvement in physical function than either intervention alone.
Abstract: BackgroundObesity exacerbates the age-related decline in physical function and causes frailty in older adults; however, the appropriate treatment for obese older adults is controversial. MethodsIn this 1-year, randomized, controlled trial, we evaluated the independent and combined effects of weight loss and exercise in 107 adults who were 65 years of age or older and obese. Participants were randomly assigned to a control group, a weight-management (diet) group, an exercise group, or a weight-management-plus-exercise (diet–exercise) group. The primary outcome was the change in score on the modified Physical Performance Test. Secondary outcomes included other measures of frailty, body composition, bone mineral density, specific physical functions, and quality of life. ResultsA total of 93 participants (87%) completed the study. In the intention-to-treat analysis, the score on the Physical Performance Test, in which higher scores indicate better physical status, increased more in the diet–exercise group tha...

859 citations


Journal ArticleDOI
TL;DR: The results of this study show that the ECHO model is an effective way to treat HCV infection in underserved communities and implementation of this model would allow other states and nations to treat a greater number of patients infected with HCV than they are currently able to treat.
Abstract: Methods We conducted a prospective cohort study comparing treatment for HCV infection at the University of New Mexico (UNM) HCV clinic with treatment by primary care clinicians at 21 ECHO sites in rural areas and prisons in New Mexico. A total of 407 patients with chronic HCV infection who had received no previous treatment for the infection were enrolled. The primary end point was a sustained virologic response. Results A total of 57.5% of the patients treated at the UNM HCV clinic (84 of 146 patients) and 58.2% of those treated at ECHO sites (152 of 261 patients) had a sustained viral response (difference in rates between sites, 0.7 percentage points; 95% confidence interval, −9.2 to 10.7; P = 0.89). Among patients with HCV genotype 1 infection, the rate of sustained viral response was 45.8% (38 of 83 patients) at the UNM HCV clinic and 49.7% (73 of 147 patients) at ECHO sites (P = 0.57). Serious adverse events occurred in 13.7% of the patients at the UNM HCV clinic and in 6.9% of the patients at ECHO sites. Conclusions The results of this study show that the ECHO model is an effective way to treat HCV infection in underserved communities. Implementation of this model would allow other states and nations to treat a greater number of patients infected with HCV than they are currently able to treat. (Funded by the Agency for Healthcare Research and Quality and others.)

840 citations


Journal ArticleDOI
08 Jun 2011-Nature
TL;DR: Conservationists should assess organisms on environmental impact rather than on whether they are natives, argue Mark Davis and 18 other ecologists.
Abstract: Conservationists should assess organisms on environmental impact rather than on whether they are natives, argue Mark Davis and 18 other ecologists.

828 citations


Journal ArticleDOI
TL;DR: This work shows that in mammalian cells, autophagy has a hitherto unappreciated positive contribution to the biogenesis and secretion of the proinflammatory cytokine IL‐1β via an export pathway that depends on Atg5, inflammasome, at least one of the two mammalian Golgi reassembly stacking protein (GRASP) paralogues, GRASP55 (GORASP2) and Rab8a.
Abstract: Autophagy controls the quality and quantity of the eukaryotic cytoplasm while performing two evolutionarily highly conserved functions: cell-autonomous provision of energy and nutrients by cytosol autodigestion during starvation, and removal of defunct organelles and large aggregates exceeding the capacity of other cellular degradative systems. In contrast to these autodigestive processes, autophagy in yeast has additional, biogenesis functions. However, no equivalent biosynthetic roles have been described for autophagy in mammals. Here, we show that in mammalian cells, autophagy has a hitherto unappreciated positive contribution to the biogenesis and secretion of the proinflammatory cytokine IL-1β via an export pathway that depends on Atg5, inflammasome, at least one of the two mammalian Golgi reassembly stacking protein (GRASP) paralogues, GRASP55 (GORASP2) and Rab8a. This process, which is a type of unconventional secretion, expands the functional manifestations of autophagy beyond autodigestive and quality control roles in mammals. It enables a subset of cytosolic proteins devoid of signal peptide sequences, and thus unable to access the conventional pathway through the ER, to enter an autophagy-based secretory pathway facilitating their exit from the cytoplasm.

789 citations


Journal ArticleDOI
TL;DR: It is reported that lysosomal positioning coordinates anabolic and catabolic responses with changes in nutrient availability by orchestrating early plasma-membrane signalling events, mTORC1 signalling and autophagy.
Abstract: The subcellular position of lysosomes, whether adjacent to the plasma membrane or perinuclear, regulates mTOR signalling and autophagy in response to nutrient availablity. Lysosomal position is regulated by changes in intracellular pH.

713 citations


Journal ArticleDOI
TL;DR: The physiological roles of GPER are highlighted in the reproductive, nervous, endocrine, immune and cardiovascular systems, as well as its pathological roles in a diverse array of disorders including cancer, for which GPER is emerging as a novel therapeutic target and prognostic indicator.
Abstract: Estrogens mediate profound effects throughout the body and regulate physiological and pathological processes in both women and men. The low prevalence of many diseases in premenopausal women is attributed to the presence of 17β-estradiol, the predominant and most potent endogenous estrogen. In addition to endogenous estrogens, several man-made and plant-derived molecules, such as bisphenol A and genistein, also exhibit estrogenic activity. Traditionally, the actions of 17β-estradiol are ascribed to two nuclear estrogen receptors (ERs), ERα and ERβ, which function as ligand-activated transcription factors. However, 17β-estradiol also mediates rapid signaling events via pathways that involve transmembrane ERs, such as G-protein-coupled ER 1 (GPER; formerly known as GPR30). In the past 10 years, GPER has been implicated in both rapid signaling and transcriptional regulation. With the discovery of GPER-selective ligands that can selectively modulate GPER function in vitro and in preclinical studies and with the use of Gper knockout mice, many more potential roles for GPER are being elucidated. This Review highlights the physiological roles of GPER in the reproductive, nervous, endocrine, immune and cardiovascular systems, as well as its pathological roles in a diverse array of disorders including cancer, for which GPER is emerging as a novel therapeutic target and prognostic indicator.

Journal ArticleDOI
TL;DR: An increasing number of sporadic cases of invasive fungal infections by non-neoformans cryptococci have been reported in immunocompromised hosts, especially for patients with advanced HIV infection or cancer who are undergoing transplant.
Abstract: A growing population of immunosuppressed patients has resulted in increasingly frequent diagnoses of invasive fungal infections, including those caused by unusual yeasts. The incidence of non-albicans species of Candida is increasing compared with that of Candida albicans, and several species, such as Candida glabrata and Candida krusei, may be resistant to azole antifungal therapy. Trichosporon species are the second most common cause of fungaemia in patients with haematological malignant disease and are characterised by resistance to amphotericin and echinocandins and poor prognosis. Rhodotorula species belong to the family Cryptococcaceae, and are a cause of catheter-related fungaemia, sepsis, and invasive disease in severely immunosuppressed patients. An increasing number of sporadic cases of invasive fungal infections by non-neoformans cryptococci have been reported in immunocompromised hosts, especially for patients with advanced HIV infection or cancer who are undergoing transplant. Other uncommon yeasts that can cause invasive disease in severely immunosuppressed patients include Geotrichum, Hansenula, Malassezia, and Saccharomyces. Host immune status is a crucial determinant of the type of invasive fungal infection a patient is at risk for. Diagnosis can be challenging and relies heavily on traditional cultures of blood and other sterile sites, although serum (1,3)-β-D-glucan testing might have an adjunctive role. Although rare yeasts are emerging as opportunistic human pathogens, diagnosis remains challenging and treatment suboptimal.

Journal ArticleDOI
TL;DR: Comparisons of subject‐specific, spatial concatenation, and group data mean subject‐level reduction strategies using PCA and probabilistic PCA (PPCA) show that computationally intensive PPCA is equivalent to PCA, and that subject‐ specific and group Data mean subject-level PCA are preferred because of well‐estimated TCs and SMs.
Abstract: Spatial independent component analysis (ICA) applied to functional magnetic resonance imaging (fMRI) data identifies functionally connected networks by estimating spatially independent patterns from their linearly mixed fMRI signals. Several multi-subject ICA approaches estimating subject-specific time courses (TCs) and spatial maps (SMs) have been developed, however, there has not yet been a full comparison of the implications of their use. Here, we provide extensive comparisons of four multi-subject ICA approaches in combination with data reduction methods for simulated and fMRI task data. For multi-subject ICA, the data first undergo reduction at the subject and group levels using principal component analysis (PCA). Comparisons of subject-specific, spatial concatenation, and group data mean subject-level reduction strategies using PCA and probabilistic PCA (PPCA) show that computationally intensive PPCA is equivalent to PCA, and that subject-specific and group data mean subject-level PCA are preferred because of well-estimated TCs and SMs. Second, aggregate independent components are estimated using either noise-free ICA or probabilistic ICA (PICA). Third, subject-specific SMs and TCs are estimated using back-reconstruction. We compare several direct group ICA (GICA) back-reconstruction approaches (GICA1-GICA3) and an indirect back-reconstruction approach, spatio-temporal regression (STR, or dual regression). Results show the earlier group ICA (GICA1) approximates STR, however STR has contradictory assumptions and may show mixed-component artifacts in estimated SMs. Our evidence-based recommendation is to use GICA3, introduced here, with subject-specific PCA and noise-free ICA, providing the most robust and accurate estimated SMs and TCs in addition to offering an intuitive interpretation.

Journal ArticleDOI
01 Nov 2011-Stroke
TL;DR: This review will describe the molecular and cellular events associated with BBB disruption and potential therapies directed toward restoring the integrity of the neurovascular unit.
Abstract: Disruptions of the blood-brain barrier (BBB) and edema formation both play key roles in the development of neurological dysfunction in acute and chronic cerebral ischemia. Animal studies have revealed the molecular cascades that are initiated with hypoxia/ischemia in the cells forming the neurovascular unit and that contribute to cell death. Matrix metalloproteinases cause reversible degradation of tight junction proteins early after the onset of ischemia, and a delayed secondary opening during a neuroinflammatory response occurring from 24 to 72 hours after. Cyclooxygenases are important in the delayed opening as the neuroinflammatory response progresses. An early opening of the BBB within the 3-hour therapeutic window for tissue-type plasminogen activator can allow it to enter the brain and increase the risk of hemorrhage. Chronic hypoxic hypoperfusion opens the BBB, which contributes to the cognitive changes seen with lacunar strokes and white matter injury in subcortical ischemic vascular disease. This review will describe the molecular and cellular events associated with BBB disruption and potential therapies directed toward restoring the integrity of the neurovascular unit.

Journal ArticleDOI
Pelin Yilmaz1, Pelin Yilmaz2, Renzo Kottmann2, Dawn Field, Rob Knight3, Rob Knight4, James R. Cole5, Linda A. Amaral-Zettler6, Jack A. Gilbert7, Jack A. Gilbert8, Jack A. Gilbert9, Ilene Karsch-Mizrachi10, Anjanette Johnston10, Guy Cochrane, Robert Vaughan, Christopher I. Hunter, Joonhong Park11, Norman Morrison12, Philippe Rocca-Serra13, Peter Sterk, Manimozhiyan Arumugam, Mark J. Bailey, Laura K. Baumgartner4, Bruce W. Birren14, Martin J. Blaser15, Vivien Bonazzi10, Timothy F. Booth, Peer Bork, Frederic D. Bushman16, Pier Luigi Buttigieg1, Pier Luigi Buttigieg2, Patrick S. G. Chain17, Patrick S. G. Chain18, Patrick S. G. Chain5, Emily S. Charlson16, Elizabeth K. Costello4, Heather Huot-Creasy19, Peter Dawyndt20, Todd Z. DeSantis21, Noah Fierer4, Jed A. Fuhrman22, Rachel E. Gallery23, Dirk Gevers14, Richard A. Gibbs24, Inigo San Gil25, Antonio Gonzalez4, Jeffrey I. Gordon26, Robert P. Guralnick4, Wolfgang Hankeln1, Wolfgang Hankeln2, Sarah K. Highlander24, Philip Hugenholtz27, Janet K. Jansson21, Janet K. Jansson18, Andrew L. Kau26, Scott T. Kelley28, Jerry Kennedy4, Dan Knights4, Omry Koren29, Justin Kuczynski4, Nikos C. Kyrpides18, Robert Larsen4, Christian L. Lauber4, Teresa M. Legg4, Ruth E. Ley29, Catherine A. Lozupone4, Wolfgang Ludwig30, Donna Lyons4, Eamonn Maguire13, Barbara A. Methé31, Folker Meyer9, Brian D. Muegge26, Sara Nakielny4, Karen E. Nelson31, Diana R. Nemergut4, Josh D. Neufeld32, Lindsay K. Newbold, Anna Oliver, Norman R. Pace4, Giriprakash Palanisamy33, Jörg Peplies, Joseph F. Petrosino24, Lita M. Proctor10, Elmar Pruesse2, Elmar Pruesse1, Christian Quast2, Jeroen Raes34, Sujeevan Ratnasingham35, Jacques Ravel19, David A. Relman36, David A. Relman37, Susanna Assunta-Sansone13, Patrick D. Schloss, Lynn M. Schriml19, Rohini Sinha16, Michelle I. Smith26, Erica Sodergren26, Aymé Spor29, Jesse Stombaugh4, James M. Tiedje5, Doyle V. Ward14, George M. Weinstock26, Doug Wendel4, Owen White19, Andrew S. Whiteley, Andreas Wilke9, Jennifer R. Wortman19, Tanya Yatsunenko26, Frank Oliver Glöckner1, Frank Oliver Glöckner2 
TL;DR: To establish a unified standard for describing sequence data and to provide a single point of entry for the scientific community to access and learn about GSC checklists, the minimum information about any (x) sequence is presented (MIxS).
Abstract: Here we present a standard developed by the Genomic Standards Consortium (GSC) for reporting marker gene sequences—the minimum information about a marker gene sequence (MIMARKS). We also introduce a system for describing the environment from which a biological sample originates. The ‘environmental packages’ apply to any genome sequence of known origin and can be used in combination with MIMARKS and other GSC checklists. Finally, to establish a unified standard for describing sequence data and to provide a single point of entry for the scientific community to access and learn about GSC checklists, we present the minimum information about any (x) sequence (MIxS). Adoption of MIxS will enhance our ability to analyze natural genetic diversity documented by massive DNA sequencing efforts from myriad ecosystems in our ever-changing biosphere.

Journal ArticleDOI
29 Sep 2011-Nature
TL;DR: Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins, and an anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations.
Abstract: The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments 1 . Among amniotes, genome sequences are available for mammals and birds 2–4 , but not for non-avian

Journal ArticleDOI
TL;DR: The concept that disease phenotype and genotype are associated with compositional changes in intestinal‐associated microbiota is supported.
Abstract: Background: Abnormal host–microbe interactions are implicated in the pathogenesis of inflammatory bowel diseases. Previous 16S rRNA sequence analysis of intestinal tissues demonstrated that a subset of Crohn's disease (CD) and ulcerative colitis (UC) samples exhibited altered intestinal-associated microbial compositions characterized by depletion of Bacteroidetes and Firmicutes (particularly Clostridium taxa). We hypothesize that NOD2 and ATG16L1 risk alleles may be associated with these alterations. Methods: To test this hypothesis, we genotyped 178 specimens collected from 35 CD, 35 UC, and 54 control patients for the three major NOD2 risk alleles (Leu 1007fs, R702W, and G908R) and the ATG16L1T300A risk allele, that had undergone previous 16S rRNA sequence analysis. Our statistical models incorporated the following independent variables: 1) disease phenotype (CD, UC, non-IBD control); 2) NOD2 composite genotype (NOD2R = at least one risk allele, NOD2NR = no risk alleles); 3) ATG16L1T300A genotype (ATG16L1R/R, ATG16L1R/NR, ATG16L1NR/NR); 4) patient age at time of surgery and all first-order interactions. The dependent variable(s) were the relative frequencies of bacterial taxa classified by applying the RDP 2.1 classifier to previously reported 16S rRNA sequence data. Results: Disease phenotype, NOD2 composite genotype and ATG16L1 genotype were significantly associated with shifts in microbial compositions by nonparametric multivariate analysis of covariance (MANCOVA). Shifts in the relative frequencies of Faecalibacterium and Escherichia taxa were significantly associated with disease phenotype by nonparametric ANCOVA. Conclusions: These results support the concept that disease phenotype and genotype are associated with compositional changes in intestinal-associated microbiota. (Inflamm Bowel Dis 2011;)

Journal ArticleDOI
TL;DR: In this paper, the authors present an iterative framework, called Press-Pulse Dynamics (PPD), that integrates the biophysical and social sciences through an understanding of how human behaviors affect "press" and "pulse" dynamics and ecosystem processes.
Abstract: The global reach of human activities affects all natural ecosystems, so that the environment is best viewed as a social–ecological system. Consequently, a more integrative approach to environmental science, one that bridges the biophysical and social domains, is sorely needed. Although models and frameworks for social–ecological systems exist, few are explicitly designed to guide a long-term interdisciplinary research program. Here, we present an iterative framework, “Press–Pulse Dynamics” (PPD), that integrates the biophysical and social sciences through an understanding of how human behaviors affect “press” and “pulse” dynamics and ecosystem processes. Such dynamics and processes, in turn, influence ecosystem services –thereby altering human behaviors and initiating feedbacks that impact the original dynamics and processes. We believe that research guided by the PPD framework will lead to a more thorough understanding of social–ecological systems and generate the knowledge needed to address pervasive environmental problems.

Journal ArticleDOI
01 Apr 2011
TL;DR: Results suggest that the influences of personalization on the privacy risk/benefit beliefs vary upon the type of personalized systems (covert and overt), and that personal characteristics moderate the parameters and path structure of the privacy calculus model.
Abstract: Despite the vast opportunities offered by location-aware marketing (LAM), mobile customers' privacy concerns appear to be a major inhibiting factor in their acceptance of LAM. This study extends the privacy calculus model to explore the personalization-privacy paradox in LAM, with considerations of personal characteristics and two personalization approaches (covert and overt). Through an experimental study, we empirically validated the proposed model. Results suggest that the influences of personalization on the privacy risk/benefit beliefs vary upon the type of personalization systems (covert and overt), and that personal characteristics moderate the parameters and path structure of the privacy calculus model.

Journal ArticleDOI
TL;DR: The potential use of BDDCS to estimate the disposition characteristics of novel chemicals (new molecular entities) in the early stages of drug discovery and development and the influence of several measured and in silico parameters in the process of B DDCS category assignment is discussed in detail.
Abstract: Here, we compile the Biopharmaceutics Drug Disposition Classification System (BDDCS) classification for 927 drugs, which include 30 active metabolites. Of the 897 parent drugs, 78.8% (707) are administered orally. Where the lowest measured solubility is found, this value is reported for 72.7% (513) of these orally administered drugs and a dose number is recorded. The measured values are reported for percent excreted unchanged in urine, LogP, and LogD 7.4 when available. For all 927 compounds, the in silico parameters for predicted Log solubility in water, calculated LogP, polar surface area, and the number of hydrogen bond acceptors and hydrogen bond donors for the active moiety are also provided, thereby allowing comparison analyses for both in silico and experimentally measured values. We discuss the potential use of BDDCS to estimate the disposition characteristics of novel chemicals (new molecular entities) in the early stages of drug discovery and development. Transporter effects in the intestine and the liver are not clinically relevant for BDDCS class 1 drugs, but potentially can have a high impact for class 2 (efflux in the gut, and efflux and uptake in the liver) and class 3 (uptake and efflux in both gut and liver) drugs. A combination of high dose and low solubility is likely to cause BDDCS class 4 to be underpopulated in terms of approved drugs (N = 53 compared with over 200 each in classes 1–3). The influence of several measured and in silico parameters in the process of BDDCS category assignment is discussed in detail.

Journal ArticleDOI
TL;DR: It is found that stream denitrification produces N2O at rates that increase with stream water nitrate (NO3−) concentrations, but that <1% of denitrified N is converted to N1O, and it is suggested that increased stream NO3− loading stimulatesDenitrification and concomitant N2o production, but does not increase the N2 O yield.
Abstract: Nitrous oxide (N2O) is a potent greenhouse gas that contributes to climate change and stratospheric ozone destruction. Anthropogenic nitrogen (N) loading to river networks is a potentially important source of N2O via microbial denitrification that converts N to N2O and dinitrogen (N2). The fraction of denitrified N that escapes as N2O rather than N2 (i.e., the N2O yield) is an important determinant of how much N2O is produced by river networks, but little is known about the N2O yield in flowing waters. Here, we present the results of whole-stream 15N-tracer additions conducted in 72 headwater streams draining multiple land-use types across the United States. We found that stream denitrification produces N2O at rates that increase with stream water nitrate (NO3−) concentrations, but that <1% of denitrified N is converted to N2O. Unlike some previous studies, we found no relationship between the N2O yield and stream water NO3−. We suggest that increased stream NO3− loading stimulates denitrification and concomitant N2O production, but does not increase the N2O yield. In our study, most streams were sources of N2O to the atmosphere and the highest emission rates were observed in streams draining urban basins. Using a global river network model, we estimate that microbial N transformations (e.g., denitrification and nitrification) convert at least 0.68 Tg·y−1 of anthropogenic N inputs to N2O in river networks, equivalent to 10% of the global anthropogenic N2O emission rate. This estimate of stream and river N2O emissions is three times greater than estimated by the Intergovernmental Panel on Climate Change.

Journal ArticleDOI
TL;DR: Overall, mortality cues appear to propel individuals toward diverging life history strategies as a function of childhood socioeconomic status, suggesting important implications for how environmental factors influence economic decisions and risky behaviors.
Abstract: Why do some people take risks and live for the present, whereas others avoid risks and save for the future? The evolutionary framework of life history theory predicts that preferences for risk and delay in gratification should be influenced by mortality and resource scarcity. A series of experiments examined how mortality cues influenced decisions involving risk preference (e.g., $10 for sure vs. 50% chance of $20) and temporal discounting (e.g., $5 now vs. $10 later). The effect of mortality depended critically on whether people grew up in a relatively resource-scarce or resource-plentiful environment. For individuals who grew up relatively poor, mortality cues led them to value the present and gamble for big immediate rewards. Conversely, for individuals who grew up relatively wealthy, mortality cues led them to value the future and avoid risky gambles. Overall, mortality cues appear to propel individuals toward diverging life history strategies as a function of childhood socioeconomic status, suggesting important implications for how environmental factors influence economic decisions and risky behaviors.

Journal ArticleDOI
TL;DR: The data indicate that better control of the metal-catalyzed transformations of the polymer into new graphitized carbon forms in the heat-treatment step will allow for even further improvement of this class of catalysts.
Abstract: In this report, we present the systematic preparation of active and durable non-precious metal catalysts (NPMCs) for the oxygen reduction reaction in polymer electrolyte fuel cells (PEFCs) based on the heat treatment of polyaniline/metal/carbon precursors. Variation of the synthesis steps, heat-treatment temperature, metal loading, and the metal type in the synthesis leads to markedly different catalyst activity, speciation, and morphology. Microscopy studies demonstrate notable differences in the carbon structure as a function of these variables. Balancing the need to increase the catalyst’s degree of graphitization through heat treatment versus the excessive loss of surface area that occurs at higher temperatures is a key to preparing an active catalyst. XPS and XAFS spectra are consistent with the presence of Me–Nx structures in both the Co and Fe versions of the catalyst, which are often proposed to be active sites. The average speciation and coordination environment of nitrogen and metal, however, depends greatly on the choice of Co or Fe. Taken together, the data indicate that better control of the metal-catalyzed transformations of the polymer into new graphitized carbon forms in the heat-treatment step will allow for even further improvement of this class of catalysts.

Journal ArticleDOI
23 Sep 2011-Science
TL;DR: This article conducted a standardized sampling in 48 herbaceous-dominated plant communities on five continents and found no clear relationship between productivity and fine-scale (meters−2) richness within sites, within regions, or across the globe.
Abstract: For more than 30 years, the relationship between net primary productivity and species richness has generated intense debate in ecology about the processes regulating local diversity. The original view, which is still widely accepted, holds that the relationship is hump-shaped, with richness first rising and then declining with increasing productivity. Although recent meta-analyses questioned the generality of hump-shaped patterns, these syntheses have been criticized for failing to account for methodological differences among studies. We addressed such concerns by conducting standardized sampling in 48 herbaceous-dominated plant communities on five continents. We found no clear relationship between productivity and fine-scale (meters−2) richness within sites, within regions, or across the globe. Ecologists should focus on fresh, mechanistic approaches to understanding the multivariate links between productivity and richness.

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TL;DR: Assessment of historical trauma and implications for research and clinical as well as community interventions, andRecommendations are concluded on ways of alleviating psychological suffering and unresolved grief among Indigenous Peoples of the Americas.
Abstract: Indigenous Peoples of the Americas have experienced devastating collective, intergenerational massive group trauma and compounding discrimination, racism, and oppression. There is increasing evidence of emotional responses to collective trauma and losses among Indigenous Peoples, which may help to inform ways of alleviating psychological suffering and unresolved grief. Tribal cultural and regional differences exist which may impact how the wounding across generations and within an individual's lifespan are experienced and addressed. This article will review the conceptual framework of historical trauma, current efforts to measure the impact of historical trauma upon emotional distress, and research as well as clinical innovations aimed at addressing historical trauma among American Indians/Alaska Natives and other Indigenous Peoples of the Americas. We will discuss assessment of historical trauma and implications for research and clinical as well as community interventions, and conclude with recommendations.

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TL;DR: In this article, the authors derived mass distributions of stellar compact remnants and provided analytical prescriptions for compact object masses for major population synthesis codes, and demonstrated that these qualitatively new results for compact objects can explain the observed gap in the remnant mass distribution between ~2-5 solar masses and place strong constraints on the nature of the supernova engine.
Abstract: The mass distribution of neutron stars and stellar-mass black holes provides vital clues into the nature of stellar core collapse and the physical engine responsible for supernova explosions. Using recent advances in our understanding of supernova engines, we derive mass distributions of stellar compact remnants. We provide analytical prescriptions for compact object masses for major population synthesis codes. In an accompanying paper, Belczynski et al., we demonstrate that these qualitatively new results for compact objects can explain the observed gap in the remnant mass distribution between ~2-5 solar masses and that they place strong constraints on the nature of the supernova engine. Here, we show that advanced gravitational radiation detectors (like LIGO/VIRGO or the Einstein Telescope) will be able to further test the supernova explosion engine models once double black hole inspirals are detected.

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TL;DR: The Large Area Telescope (LAT) aboard the Fermi Gamma-ray Space Telescope provides an unprecedented opportunity to study gamma-ray blazars as mentioned in this paper, and a large-scale, fast-cadence 15 GHz radio monitoring program with the 40 m telescope at the Owens Valley Radio Observatory.
Abstract: The Large Area Telescope (LAT) aboard the Fermi Gamma-ray Space Telescope provides an unprecedented opportunity to study gamma-ray blazars. To capitalize on this opportunity, beginning in late 2007, about a year before the start of LAT science operations, we began a large-scale, fast-cadence 15 GHz radio monitoring program with the 40 m telescope at the Owens Valley Radio Observatory. This program began with the 1158 northern (δ > –20°) sources from the Candidate Gamma-ray Blazar Survey and now encompasses over 1500 sources, each observed twice per week with about 4 mJy (minimum) and 3% (typical) uncertainty. Here, we describe this monitoring program and our methods, and present radio light curves from the first two years (2008 and 2009). As a first application, we combine these data with a novel measure of light curve variability amplitude, the intrinsic modulation index, through a likelihood analysis to examine the variability properties of subpopulations of our sample. We demonstrate that, with high significance (6σ), gamma-ray-loud blazars detected by the LAT during its first 11 months of operation vary with almost a factor of two greater amplitude than do the gamma-ray-quiet blazars in our sample. We also find a significant (3σ) difference between variability amplitude in BL Lacertae objects and flat-spectrum radio quasars (FSRQs), with the former exhibiting larger variability amplitudes. Finally, low-redshift (z < 1) FSRQs are found to vary more strongly than high-redshift FSRQs, with 3σ significance. These findings represent an important step toward understanding why some blazars emit gamma-rays while others, with apparently similar properties, remain silent.

01 Aug 2011
TL;DR: The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments as discussed by the authors.
Abstract: The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments 1 . Among amniotes, genome sequences are available for mammals and birds 2–4 , but not for non-avian

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TL;DR: The wish list of clinicians for the modulation of FRAX is large, but in many instances, these wishes cannot presently be fulfilled; however, an explanation and understanding of the reasons may be helpful in translating the information provided by FRAx into clinical practice.
Abstract: The introduction of the WHO FRAX® algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. Its use in fracture risk prediction has strengths, but also limitations of which the clinician should be aware and are the focus of this review The International Osteoporosis Foundation (IOF) and the International Society for Clinical Densitometry (ISCD) appointed a joint Task Force to develop resource documents in order to make recommendations on how to improve FRAX and better inform clinicians who use FRAX. The Task Force met in November 2010 for 3 days to discuss these topics which form the focus of this review. This study reviews the resource documents and joint position statements of ISCD and IOF. Details on the clinical risk factors currently used in FRAX are provided, and the reasons for the exclusion of others are provided. Recommendations are made for the development of surrogate models where country-specific FRAX models are not available. The wish list of clinicians for the modulation of FRAX is large, but in many instances, these wishes cannot presently be fulfilled; however, an explanation and understanding of the reasons may be helpful in translating the information provided by FRAX into clinical practice.

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Georges Aad1, Brad Abbott2, Jalal Abdallah3, A. A. Abdelalim4  +3034 moreInstitutions (179)
TL;DR: In this article, a search for squarks and gluinos in final states containing jets, missing transverse momentum and no electrons or muons is presented, and the data were recorded by the ATLAS experiment in sqrt(s) = 7 TeV proton-proton collisions at the Large Hadron Collider.