Showing papers by "Brown University published in 2006"
TL;DR: In this article, a simple cosmological model with only six parameters (matter density, Omega_m h^2, baryon density, BH density, Hubble Constant, H_0, amplitude of fluctuations, sigma_8, optical depth, tau, and a slope for the scalar perturbation spectrum, n_s) was proposed to fit the three-year WMAP temperature and polarization data.
Abstract: A simple cosmological model with only six parameters (matter density, Omega_m h^2, baryon density, Omega_b h^2, Hubble Constant, H_0, amplitude of fluctuations, sigma_8, optical depth, tau, and a slope for the scalar perturbation spectrum, n_s) fits not only the three year WMAP temperature and polarization data, but also small scale CMB data, light element abundances, large-scale structure observations, and the supernova luminosity/distance relationship. Using WMAP data only, the best fit values for cosmological parameters for the power-law flat LCDM model are (Omega_m h^2, Omega_b h^2, h, n_s, tau, sigma_8) = 0.1277+0.0080-0.0079, 0.02229+-0.00073, 0.732+0.031-0.032, 0.958+-0.016, 0.089+-0.030, 0.761+0.049-0.048). The three year data dramatically shrink the allowed volume in this six dimensional parameter space. Assuming that the primordial fluctuations are adiabatic with a power law spectrum, the WMAP data_alone_ require dark matter, and favor a spectral index that is significantly less than the Harrison-Zel'dovich-Peebles scale-invariant spectrum (n_s=1, r=0). Models that suppress large-scale power through a running spectral index or a large-scale cut-off in the power spectrum are a better fit to the WMAP and small scale CMB data than the power-law LCDM model: however, the improvement in the fit to the WMAP data is only Delta chi^2 = 3 for 1 extra degree of freedom. The combination of WMAP and other astronomical data yields significant constraints on the geometry of the universe, the equation of state of the dark energy, the gravitational wave energy density, and neutrino properties. Consistent with the predictions of simple inflationary theories, we detect no significant deviations from Gaussianity in the CMB maps.
6,002 citations
TL;DR: Initial results for a tetraplegic human using a pilot NMP suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis.
Abstract: Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a ‘neural cursor’ with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis. The cover shows Matt Nagle, first participant in the BrainGate pilot clinical trial. He is unable to move his arms or legs following cervical spinal cord injury. Researchers at the Department of Neuroscience at Brown University, working with biotech company Cyberkinetics and 3 other institutions, demonstrate that movement-related signals can be relayed from the brain via an implanted BrainGate chip, allowing the patient to drive a computer screen cursor and activate simple robotic devices. Such neuromotor prostheses could pave the way towards systems to replace or restore lost motor function in paralysed humans. Prior to this advance, this type of work has been performed chiefly in monkeys. The latest example of such research has achieved a large increase in speed over current devices, enhancing the prospects for clinically viable brain-machine interfaces.
3,120 citations
Cleveland Clinic1, University of Edinburgh2, Heidelberg University3, Duke University4, Rush University Medical Center5, Hartford Hospital6, Pierre-and-Marie-Curie University7, University of Toronto8, Harvard University9, Brown University10, Imperial College London11, University of Texas Health Science Center at San Antonio12, University of Western Australia13, Gleneagles Hospital14, University of Rochester15, University of Paris16, University of Kentucky17, SUNY Downstate Medical Center18, Case Western Reserve University19
TL;DR: In this article, the authors compared the effect of clopidogrel and low-dose aspirin on the rate of myocardial infarction, stroke, or death from cardiovascular causes.
Abstract: Background Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events. Methods We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes. Results The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P = 0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P = 0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P = 0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P = 0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P = 0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P = 0.046). Conclusions In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes. (ClinicalTrials.gov number, NCT00050817.)
2,464 citations
Brown University1, Stanford University2, University of New Mexico3, University of Connecticut4, University of Southern California5, University of California, Merced6, University of Washington7, National Science Foundation8, Los Alamos National Laboratory9, Rutgers University10, Columbia University11, University of Bergen12, Portland State University13, University of Kansas14
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
TL;DR: In this paper, the authors proposed a rank test based on matrix perturbation theory, which overcomes deficiencies of existing rank statistics, such as: a Kronecker covariance matrix for the canonical correlation rank statistic of Anderson [Annals of Mathematical Statistics (1951), 22, 327-351] sensitivity to the ordering of the variables for the LDU rank statistics of Cragg and Donald [1996, 91, 1301-1309] and Gill and Lewbel [Journal of the American Statistical Association (1992), 87, 766-776] a limiting
2,125 citations
TL;DR: It is found that one-trial inhibitory avoidance learning in rats produced the same changes in hippocampal glutamate receptors as induction of LTP with HFS and caused a spatially restricted increase in the amplitude of evoked synaptic transmission in CA1 in vivo.
Abstract: Years of intensive investigation have yielded a sophisticated understanding of long-term potentiation (LTP) induced in hippocampal area CA1 by high-frequency stimulation (HFS). These efforts have been motivated by the belief that similar synaptic modifications occur during memory formation, but it has never been shown that learning actually induces LTP in CA1. We found that one-trial inhibitory avoidance learning in rats produced the same changes in hippocampal glutamate receptors as induction of LTP with HFS and caused a spatially restricted increase in the amplitude of evoked synaptic transmission in CA1 in vivo. Because the learning-induced synaptic potentiation occluded HFS-induced LTP, we conclude that inhibitory avoidance training induces LTP in CA1.
1,818 citations
Ohio State University1, Fred Hutchinson Cancer Research Center2, University of Cincinnati3, University of Iowa4, University of California, Davis5, University of Alabama at Birmingham6, University of Arizona7, University of Washington8, Rush University Medical Center9, Wake Forest University10, University of Nevada, Reno11, University of Texas at San Antonio12, Kaiser Permanente13, University of Pittsburgh14, University of California, Los Angeles15, Stony Brook University16, Baylor College of Medicine17, University of North Carolina at Chapel Hill18, Wayne State University19, Howard University20, George Washington University21, University of California, Irvine22, University of Tennessee Health Science Center23, Medical College of Wisconsin24, University of California, San Diego25, Rutgers University26, University of Florida27, National Institutes of Health28, Harvard University29, University of Minnesota30, University of Massachusetts Boston31, University of Miami32, Emory University33, University of Wisconsin-Madison34, Stanford University35, Northwestern University36, University at Buffalo37, Brown University38, Yeshiva University39
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
TL;DR: MDR tuberculosis is more prevalent than previously realised in a rural area in KwaZulu Natal, South Africa and has been transmitted to HIV co-infected patients and is associated with high mortality.
1,601 citations
Medical University of South Carolina1, Yale University2, Boston University3, University of Wisconsin–Milwaukee4, University of North Carolina at Chapel Hill5, University of Washington6, Harvard University7, University of Texas at San Antonio8, Brown University9, University of Miami10, National Institutes of Health11, University of New Mexico12, University of Pennsylvania13
TL;DR: Patients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI.
Abstract: ContextAlcohol dependence treatment may include medications, behavioral therapies, or both. It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings.ObjectivesTo evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome.Design, Setting, and ParticipantsRandomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence.InterventionsEight groups of patients received medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a combined behavioral intervention (CBI). A ninth group received CBI only (no pills). Patients were also evaluated for up to 1 year after treatment.Main Outcome MeasuresPercent days abstinent from alcohol and time to first heavy drinking day.ResultsAll groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n = 302), CBI plus medical management and placebos (n = 305), or both naltrexone and CBI plus medical management (n = 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only (n = 305), a significant naltrexone × behavioral intervention interaction (P = .009). Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P = .02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management (n = 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone (n = 153) or placebo plus medical management and CBI (n = 156) (73.8 and 79.8, respectively; P<.001). One year after treatment, these between-group effects were similar but no longer significant.ConclusionsPatients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI. No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management. Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment. Naltrexone with medical management could be delivered in health care settings, thus serving alcohol-dependent patients who might otherwise not receive treatment.Trial Registrationclinicaltrials.gov Identifier: NCT00006206
1,584 citations
TL;DR: Global mineralogical mapping of Mars by the Observatoire pour la Mineralogie, l'Eau, les Glaces et l'Activite (OMEGA) instrument on the European Space Agency's Mars Express spacecraft provides new information on Mars' geological and climatic history.
Abstract: Global mineralogical mapping of Mars by the Observatoire pour la Mineralogie, l'Eau, les Glaces et l'Activite (OMEGA) instrument on the European Space Agency's Mars Express spacecraft provides new information on Mars' geological and climatic history. Phyllosilicates formed by aqueous alteration very early in the planet's history (the "phyllocian" era) are found in the oldest terrains; sulfates were formed in a second era (the "theiikian" era) in an acidic environment. Beginning about 3.5 billion years ago, the last era (the "siderikian") is dominated by the formation of anhydrous ferric oxides in a slow superficial weathering, without liquid water playing a major role across the planet.
1,480 citations
TL;DR: Among more severely depressed patients, behavioral activation was comparable to antidepressant medication, and both significantly outperformed cognitive therapy, and the implications of current treatment guidelines and dissemination are discussed.
Abstract: Antidepressant medication is considered the current standard for severe depression, and cognitive therapy is the most widely investigated psychosocial treatment for depression. However, not all patients want to take medication, and cognitive therapy has not demonstrated consistent efficacy across trials. Moreover, dismantling designs have suggested that behavioral components may account for the efficacy of cognitive therapy. The present study tested the efficacy of behavioral activation by comparing it with cognitive therapy and antidepressant medication in a randomized placebo-controlled design in adults with major depressive disorder (N = 241). In addition, it examined the importance of initial severity as a moderator of treatment outcome. Among more severely depressed patients, behavioral activation was comparable to antidepressant medication, and both significantly outperformed cognitive therapy. The implications of these findings for the evaluation of current treatment guidelines and dissemination are discussed.
TL;DR: All estrogen receptor and RNA polymerase II binding sites are mapped on a genome-wide scale, identifying the authentic cis binding sites and target genes, in breast cancer cells, and distinct temporal mechanisms of estrogen-mediated gene regulation are demonstrated.
Abstract: The estrogen receptor is the master transcriptional regulator of breast cancer phenotype and the archetype of a molecular therapeutic target. We mapped all estrogen receptor and RNA polymerase II binding sites on a genome-wide scale, identifying the authentic cis binding sites and target genes, in breast cancer cells. Combining this unique resource with gene expression data demonstrates distinct temporal mechanisms of estrogen-mediated gene regulation, particularly in the case of estrogen-suppressed genes. Furthermore, this resource has allowed the identification of cis-regulatory sites in previously unexplored regions of the genome and the cooperating transcription factors underlying estrogen signaling in breast cancer.
TL;DR: In this paper, the impact of national bank concentration, bank regulations, and national institutions on the likelihood of a country suffering a systemic banking crisis was studied using data on 69 countries from 1980 to 1997.
Abstract: Motivated by public policy debates about bank consolidation and conflicting theoretical predictions about the relationship between bank concentration, bank competition and banking system fragility, this paper studies the impact of national bank concentration, bank regulations, and national institutions on the likelihood of a country suffering a systemic banking crisis. Using data on 69 countries from 1980 to 1997, we find that crises are less likely in economies with more concentrated banking systems even after controlling for differences in commercial bank regulatory policies, national institutions affecting competition, macroeconomic conditions, and shocks to the economy. Furthermore, the data indicate that regulatory policies and institutions that thwart competition are associated with greater banking system fragility.
TL;DR: The findings demonstrate the diagnostic heterogeneity of adolescents engaging in NSSI, highlight the significant overlap between N SSI and suicide attempts, and provide a point of departure for future research aimed at elucidating the relations between non-suicidal and suicidal self-injury.
Abstract: Non-suicidal self-injury (NSSI) is a prevalent behavioral problem, yet many fundamental aspects of NSSI remain unknown. This case series study reports on the diagnostic correlates of adolescents with a recent history of NSSI and examines the relation between NSSI and suicide attempts. Data are from clinical interviews with 89 adolescents admitted to an adolescent psychiatric inpatient unit who engaged in NSSI in the previous 12 months. Results revealed that 87.6% of adolescents engaging in NSSI met criteria for a DSM-IVAxis I diagnosis (M=3.0, S.D.=2.2, range=0 to 8 diagnoses), including externalizing (62.9%), internalizing (51.7%), and substance use (59.6%) disorders. Most adolescents assessed also met criteria for an Axis II personality disorder (67.3%). Overall, 70% of adolescents engaging in NSSI reported a lifetime suicide attempt and 55% reported multiple attempts. Characteristics of NSSI associated with making suicide attempts included a longer history of NSSI, use of a greater number of methods, and absence of physical pain during NSSI. These findings demonstrate the diagnostic heterogeneity of adolescents engaging in NSSI, highlight the significant overlap between NSSI and suicide attempts, and provide a point of departure for future research aimed at elucidating the relations between non-suicidal and suicidal self-injury. © 2006 Elsevier Ireland Ltd. All rights reserved.
TL;DR: The Global Initiative for Asthma has outlined a six-point patient management plan to address the effective handling of the increased number of patients in primary care, focusing on patient education, written treatment plans, and ongoing communication and review with patients and their providers.
TL;DR: It is suggested that growth velocity during an ELBW infant’s NICU hospitalization exerts a significant, and possibly independent, effect on neurodevelopmental and growth outcomes at 18 to 22 months’ corrected age.
Abstract: OBJECTIVES. The objectives of this study were to assess whether (1) in-hospital growth velocity is predictive of neurodevelopmental and growth outcomes at 18 to 22 months’ corrected age among extremely low birth weight (ELBW) infants and (2) in-hospital growth velocity contributes to these outcomes after controlling for confounding demographic and clinical variables. METHODS. Infants 501 to 1000 g birth weight from a multicenter cohort study were divided into quartiles of in-hospital growth velocity rates. Variables considered for the logistic-regression models included gender, race, gestational age, small for gestational age, mother’s education, severe intraventricular hemorrhage, periventricular leukomalacia, age at regaining birth weight, necrotizing enterocolitis, late-onset infection, bronchopulmonary dysplasia, postnatal steroid therapy for pulmonary disease, and center. RESULTS. Of the 600 discharged infants, 495 (83%) were evaluated at 18 to 22 months’ corrected age. As the rate of weight gain increased between quartile 1 and quartile 4, from 12.0 to 21.2 g/kg per day, the incidence of cerebral palsy, Bayley II Mental Developmental Index (MDI) CONCLUSIONS. These analyses suggest that growth velocity during an ELBW infant’s NICU hospitalization exerts a significant, and possibly independent, effect on neurodevelopmental and growth outcomes at 18 to 22 months’ corrected age.
TL;DR: The HTTLPR L(A)L( a) genotype exerts a moderate effect on risk of OCD, which crystallizes the evidence that the HTT gene has a role in OCD.
Abstract: A functional serotonin transporter promoter polymorphism, HTTLPR, alters the risk of disease as well as brain morphometry and function. Here, we show that HTTLPR is functionally triallelic. The LG allele, which is the L allele with a common G substitution, creates a functional AP2 transcription-factor binding site. Expression assays in 62 lymphoblastoid cell lines representing the six genotypes and in transfected raphe-derived cells showed codominant allele action and low, nearly equivalent expression for the S and LG alleles, accounting for more variation in HTT expression than previously recognized. The gain-of-function LALA genotype was approximately twice as common in 169 whites with obsessive-compulsive disorder (OCD) than in 253 ethnically matched controls. We performed a replication study in 175 trios consisting of probands with OCD and their parents. The LA allele was twofold overtransmitted to the patients with OCD. The HTTLPR LALA genotype exerts a moderate (1.8-fold) effect on risk of OCD, which crystallizes the evidence that the HTT gene has a role in OCD.
Erica Sodergren1, George M. Weinstock1, Eric H. Davidson2, R. Andrew Cameron2 +243 more•Institutions (51)
TL;DR: The sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus is reported, a model for developmental and systems biology and yields insights into the evolution of deuterostomes.
Abstract: We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
TL;DR: The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL, making delivery of state-of-the-art care challenging.
Abstract: Context Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society–USA panel has updated its recommendations as warranted by new developments in the field. Objective To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIVinfected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described. Data Sources and Study Selection A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel. Data Extraction and Synthesis Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel. Conclusions Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/µL and before it declines to 200/µL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced.
TL;DR: Because of better survival after asystole and PEA, children had better outcomes than adults despite fewer cardiac arrests due to VF or pulseless VT, according to this multicenter registry of in-hospital cardiac arrest.
Abstract: ContextCardiac arrests in adults are often due to ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), which are associated with better outcomes than asystole or pulseless electrical activity (PEA). Cardiac arrests in children are typically asystole or PEA.ObjectiveTo test the hypothesis that children have relatively fewer in-hospital cardiac arrests associated with VF or pulseless VT compared with adults and, therefore, worse survival outcomes.Design, Setting, and PatientsA prospective observational study from a multicenter registry (National Registry of Cardiopulmonary Resuscitation) of cardiac arrests in 253 US and Canadian hospitals between January 1, 2000, and March 30, 2004. A total of 36 902 adults (≥18 years) and 880 children (<18 years) with pulseless cardiac arrests requiring chest compressions, defibrillation, or both were assessed. Cardiac arrests occurring in the delivery department, neonatal intensive care unit, and in the out-of-hospital setting were excluded.Main Outcome MeasureSurvival to hospital discharge.ResultsThe rate of survival to hospital discharge following pulseless cardiac arrest was higher in children than adults (27% [236/880] vs 18% [6485/36 902]; adjusted odds ratio [OR], 2.29; 95% confidence interval [CI], 1.95-2.68). Of these survivors, 65% (154/236) of children and 73% (4737/6485) of adults had good neurological outcome. The prevalence of VF or pulseless VT as the first documented pulseless rhythm was 14% (120/880) in children and 23% (8361/36 902) in adults (OR, 0.54; 95% CI, 0.44-0.65; P<.001). The prevalence of asystole was 40% (350) in children and 35% (13 024) in adults (OR, 1.20; 95% CI, 1.10-1.40; P = .006), whereas the prevalence of PEA was 24% (213) in children and 32% (11 963) in adults (OR, 0.67; 95% CI, 0.57-0.78; P<.001). After adjustment for differences in preexisting conditions, interventions in place at time of arrest, witnessed and/or monitored status, time to defibrillation of VF or pulseless VT, intensive care unit location of arrest, and duration of cardiopulmonary resuscitation, only first documented pulseless arrest rhythm remained significantly associated with differential survival to discharge (24% [135/563] in children vs 11% [2719/24 987] in adults with asystole and PEA; adjusted OR, 2.73; 95% CI, 2.23-3.32).ConclusionsIn this multicenter registry of in-hospital cardiac arrest, the first documented pulseless arrest rhythm was typically asystole or PEA in both children and adults. Because of better survival after asystole and PEA, children had better outcomes than adults despite fewer cardiac arrests due to VF or pulseless VT.
TL;DR: In this article, the authors explored the contribution of changes in weight, diet, and physical activity on the risk of developing diabetes among ILS participants, and found that weight loss was the dominant predictor of reduced diabetes incidence (hazard ratio per 5-kg weight loss 0.42 [95% CI 0.35-0.51]; P < 0.0001).
Abstract: OBJECTIVE —Diabetes Prevention Program (DPP) participants randomized to the intensive lifestyle intervention (ILS) had significantly reduced risk of diabetes compared with placebo participants. We explored the contribution of changes in weight, diet, and physical activity on the risk of developing diabetes among ILS participants.
RESEARCH DESIGN AND METHODS —For this study, we analyzed one arm of a randomized trial using Cox proportional hazards regression over 3.2 years of follow-up.
RESULTS —A total of 1,079 participants were aged 25–84 years (mean 50.6 years, BMI 33.9 kg/m2). Weight loss was the dominant predictor of reduced diabetes incidence (hazard ratio per 5-kg weight loss 0.42 [95% CI 0.35–0.51]; P < 0.0001). For every kilogram of weight loss, there was a 16% reduction in risk, adjusted for changes in diet and activity. Lower percent of calories from fat and increased physical activity predicted weight loss. Increased physical activity was important to help sustain weight loss. Among 495 participants not meeting the weight loss goal at year 1, those who achieved the physical activity goal had 44% lower diabetes incidence.
CONCLUSIONS —Interventions to reduce diabetes risk should primarily target weight reduction.
Howard University1, Memorial Hospital of South Bend2, Northwestern University3, George Washington University4, Harvard University5, Stanford University6, Yeshiva University7, University of Pittsburgh8, Fred Hutchinson Cancer Research Center9, University of California, San Diego10, Rutgers University11, University of Alabama at Birmingham12, University of Florida13, University of Minnesota14, Ohio State University15, University of Massachusetts Medical School16, University of Miami17, Emory University18, University of California, Davis19, National Institutes of Health20, University of Wisconsin-Madison21, University of Iowa22, Kaiser Permanente23, University at Buffalo24, Wake Forest University25, Pfizer26, Brown University27, University of Arizona28, Rush University Medical Center29, University of Nevada, Reno30, University of Texas at San Antonio31, University of California, Los Angeles32, University of Cincinnati33, Stony Brook University34, Baylor College of Medicine35, University of North Carolina at Chapel Hill36, Wayne State University37, University of California, Irvine38, University of Tennessee Health Science Center39, Medical College of Wisconsin40
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
University of Alaska Fairbanks1, Woods Hole Research Center2, University of California3, Marine Biological Laboratory4, University of Missouri5, Oregon State University6, National Center for Atmospheric Research7, Max Planck Society8, University of New Hampshire9, United States Geological Survey10, Cornell University11, Stanford University12, University of Colorado Boulder13, United States Forest Service14, Brown University15, Duke University16
TL;DR: In this article, the imbalance between gross primary production (GPP) and ecosystem respiration (ER) was defined as a measure of the amount of carbon being transferred from one ecosystem to another.
Abstract: Recent projectionsofclimatic change havefocused a great deal of scientific and public attention on patterns of carbon (C) cycling as well as its controls, particularly the factors that determine whether an ecosystem is a net source or sink of atmospheric carbon dioxide (CO2). Net ecosystem production (NEP), a central concept in C-cycling research, has been used by scientists to represent two different concepts. We propose that NEP be restricted to just one of its two original definitions—the imbalance between gross primary production (GPP) and ecosystem respiration (ER). We further propose that a new term—net ecosystem carbon balance (NECB)—be applied to the net rate of C accumulation in (or loss from [negative sign]) ecosystems. Net ecosystem carbon balance differs from NEP when C fluxesotherthanCfixationandrespiration occur,or when inorganic C enters or leaves in dissolved form. These fluxes include the leaching loss or lateral transfer of C from the ecosystem; the emission of volatile organic C, methane, and carbon monoxide; and the release of soot and CO2 from fire. Carbon fluxes in addition to NEP are particularly important determinants of NECB over long time scales. However, even over short time scales, they are important in ecosystems such as streams, estuaries, wetlands, and cities. Recent technological advances have led to a diversity of approaches to the measurement of C fluxes at different temporal and spatial scales. These approaches frequently capture different components of NEP or NECB and can therefore be compared across scales only by carefully specifying the
TL;DR: In this paper, the authors investigated telomere dysfunction, a recently discovered biomarker of cellular senescence, and found that the number of senescent fibroblasts increases exponentially in the skin of aging baboons, reaching >15% of all cells in very old individuals.
Abstract: The aging of organisms is characterized by a gradual functional decline of all organ systems. Mammalian somatic cells in culture display a limited proliferative life span, at the end of which they undergo an irreversible cell cycle arrest known as replicative senescence. Whether cellular senescence contributes to organismal aging has been controversial. We investigated telomere dysfunction, a recently discovered biomarker of cellular senescence, and found that the number of senescent fibroblasts increases exponentially in the skin of aging baboons, reaching >15% of all cells in very old individuals. In addition, the same cells contain activated ataxia-telangiectasia mutated kinase and heterochromatinized nuclei, confirming their senescent status.
TL;DR: In this paper, a review of recent advances in chemical synthesis, self-assembly, and potential applications of monodisperse binary FePt nanoparticles is presented. And the surface, structural, and magnetic properties of these nanoparticles are discussed, along with three potential applications in data storage, permanent magnetic nanocomposites, and biomedicine.
Abstract: This paper reviews recent advances in chemical synthesis, self-assembly, and potential applications of monodisperse binary FePt nanoparticles. After a brief introduction to nanomagnetism and conventional processes of fabricating FePt nanoparticles, the paper focuses on recent developments in solution-phase syntheses of monodisperse FePt nanoparticles and their self-assembly into nanoparticle superlattices. The paper further outlines the surface, structural, and magnetic properties of the FePt nanoparticles and gives examples of three potential applications in data storage, permanent magnetic nanocomposites, and biomedicine.
TL;DR: This review critically assesses the hypothesis that the reinforcing effect of virtually all drugs of abuse is primarily dependent on activation of the mesolimbic dopamine system and indicates that increased dopamine transmission is clearly both necessary and sufficient to promote psychostimulant reinforcement.
TL;DR: The moduli space of positive representations is a topologically trivial open domain in the space of all representations as discussed by the authors, and all positive representations of the fundamental group of S to G(R) are faithful, discrete and positive hyperbolic.
Abstract: Let G be a split semisimple algebraic group over Q with trivial center. Let S be a compact oriented surface, with or without boundary. We define positive representations of the fundamental group of S to G(R), construct explicitly all positive representations, and prove that they are faithful, discrete, and positive hyperbolic; the moduli space of positive representations is a topologically trivial open domain in the space of all representations. When S have holes, we defined two moduli spaces closely related to the moduli spaces of G-local systems on S. We show that they carry a lot of interesting structures. In particular we define a distinguished collection of coordinate systems, equivariant under the action of the mapping class group of S. We prove that their transition functions are subtraction free. Thus we have positive structures on these moduli spaces. Therefore we can take their points with values in any positive semifield. Their positive real points provide the two higher Teichmuller spaces related to G and S, while the points with values in the tropical semifields provide the lamination spaces. We define the motivic avatar of the Weil–Petersson form for one of these spaces. It is related to the motivic dilogarithm.
TL;DR: Staining patterns after monocular enucleation revealed that the projections of these cells are overwhelmingly crossed except for the projection to the SCN, which is bilaterally symmetrical, and that other ganglion cells do contribute at least some retinal input to these targets.
Abstract: A rare type of ganglion cell in mammalian retina is directly photosensitive. These novel retinal photoreceptors express the photopigment melanopsin. They send axons directly to the suprachiasmatic nucleus (SCN), intergeniculate leaflet (IGL), and olivary pretectal nucleus (OPN), thereby contributing to photic synchronization of circadian rhythms and the pupillary light reflex. Here, we sought to characterize more fully the projections of these cells to the brain. By targeting tau-lacZ to the melanopsin gene locus in mice, ganglion cells that would normally express melanopsin were induced to express, instead, the marker enzyme beta-galactosidase. Their axons were visualized by X-gal histochemistry or anti-beta-galactosidase immunofluorescence. Established targets were confirmed, including the SCN, IGL, OPN, ventral division of the lateral geniculate nucleus (LGv), and preoptic area, but the overall projections were more widespread than previously recognized. Targets included the lateral nucleus, peri-supraoptic nucleus, and subparaventricular zone of the hypothalamus, medial amygdala, margin of the lateral habenula, posterior limitans nucleus, superior colliculus, and periaqueductal gray. There were also weak projections to the margins of the dorsal lateral geniculate nucleus. Co-staining with the cholera toxin B subunit to label all retinal afferents showed that melanopsin ganglion cells provide most of the retinal input to the SCN, IGL, and lateral habenula and much of that to the OPN, but that other ganglion cells do contribute at least some retinal input to these targets. Staining patterns after monocular enucleation revealed that the projections of these cells are overwhelmingly crossed except for the projection to the SCN, which is bilaterally symmetrical.
TL;DR: The interface between an infectious agent and its host represents the ultimate battleground for survival: the microbe must secure a niche for replication, whereas the host must limit the pathogen's advance.
Abstract: The interface between an infectious agent and its host represents the ultimate battleground for survival: The microbe must secure a niche for replication, whereas the host must limit the pathogen's advance. Among the host's arsenal of antimicrobial factors, the type 1 interferons (IFNs) induce potent defense mechanisms against viruses and are key in the host-virus standoff. Viruses have evolved multiple tricks to avoid the immediate antiviral effects of IFNs and, in turn, hosts have adapted use of this innate cytokine system to galvanize multiple additional layers of immune defense. The plasticity that exists in these interactions provides us with a lesson in detente.
TL;DR: Results show youth depression treatments appear to produce effects that are significant but modest in their strength, breadth, and durability, and Cognitive treatments (e.g., cognitive-behavioral therapy) fared no better than noncognitive approaches.
Abstract: Serious sequelae of youth depression, plus recent concerns over medication safety, prompt growing interest in the effects of youth psychotherapy. In previous meta-analyses, effect sizes (ESs) have averaged .99, well above conventional standards for a large effect and well above mean ES for other conditions. The authors applied rigorous analytic methods to the largest study sample to date and found a mean ES of .34, not superior but significantly inferior to mean ES for other conditions. Cognitive treatments (e.g., cognitive-behavioral therapy) fared no better than noncognitive approaches. Effects showed both generality (anxiety was reduced) and specificity (externalizing problems were not), plus short- but not long-term holding power. Youth depression treatments appear to produce effects that are significant but modest in their strength, breadth, and durability.