Showing papers by "Case Western Reserve University published in 2011"
TL;DR: The GRADE process begins with asking an explicit question, including specification of all important outcomes, and provides explicit criteria for rating the quality of evidence that include study design, risk of bias, imprecision, inconsistency, indirectness, and magnitude of effect.
6,093 citations
TL;DR: The approach of GRADE to rating quality of evidence specifies four categories-high, moderate, low, and very low-that are applied to a body of evidence, not to individual studies.
5,228 citations
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08 Sep 2011TL;DR: A two-dimensional classificatory scheme highlighting ten different approaches to the measurement of business performance in strategy research is developed in this article, where the first dimension concerns the use of financial versus broader operational criteria, while the second dimension focuses on two alternate data sources (primary versus secondary).
Abstract: A two-dimensional classificatory scheme highlighting ten different approaches to the measurement of business performance in strategy research is developed. The first dimension concerns the use of financial versus broader operational criteria, while the second focuses on two alternate data sources (primary versus secondary). The scheme permits the classification of an exhaustive coverage of measurement approaches and is useful for discussing their relative merits and demerits. Implications for operationalizing business performance in future strategy research are discussed.
3,475 citations
Daniel J. Eisenstein1, Daniel J. Eisenstein2, David H. Weinberg3, Eric Agol4 +260 more•Institutions (62)
TL;DR: SDSS-III as mentioned in this paper is a program of four spectroscopic surveys on three scientific themes: dark energy and cosmological parameters, the history and structure of the Milky Way, and the population of giant planets around other stars.
Abstract: Building on the legacy of the Sloan Digital Sky Survey (SDSS-I and II), SDSS-III is a program of four spectroscopic surveys on three scientific themes: dark energy and cosmological parameters, the history and structure of the Milky Way, and the population of giant planets around other stars. In keeping with SDSS tradition, SDSS-III will provide regular public releases of all its data, beginning with SDSS DR8 (which occurred in Jan 2011). This paper presents an overview of the four SDSS-III surveys. BOSS will measure redshifts of 1.5 million massive galaxies and Lya forest spectra of 150,000 quasars, using the BAO feature of large scale structure to obtain percent-level determinations of the distance scale and Hubble expansion rate at z 100 per resolution element), H-band (1.51-1.70 micron) spectra of 10^5 evolved, late-type stars, measuring separate abundances for ~15 elements per star and creating the first high-precision spectroscopic survey of all Galactic stellar populations (bulge, bar, disks, halo) with a uniform set of stellar tracers and spectral diagnostics. MARVELS will monitor radial velocities of more than 8000 FGK stars with the sensitivity and cadence (10-40 m/s, ~24 visits per star) needed to detect giant planets with periods up to two years, providing an unprecedented data set for understanding the formation and dynamical evolution of giant planet systems. (Abridged)
2,265 citations
McMaster University1, University Hospital of Basel2, Autonomous University of Barcelona3, Mayo Clinic4, University at Buffalo5, University of South Florida6, Case Western Reserve University7, Oregon Health & Science University8, Duke University9, United States Department of Veterans Affairs10, University Medical Center Freiburg11
TL;DR: In the GRADE approach, randomized trials start as high-quality evidence and observational studies as low- quality evidence, but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias.
2,059 citations
TL;DR: A meta-analysis of 193 studies was conducted to examine the strength of the association between mothers’ depression and children’s behavioral problems or emotional functioning, with implications for theoretical models that move beyond main effects models in order to more accurately identify which children of depressed mothers are more or less at risk for specific outcomes.
Abstract: Although the association between maternal depression and adverse child outcomes is well established, the strength of the association, the breadth or specificity of the outcomes, and the role of moderators are not known This information is essential to inform not only models of risk but also the design of preventive interventions by helping to identify subgroups at greater risk than others and to elucidate potential mechanisms as targets of interventions A meta-analysis of 193 studies was conducted to examine the strength of the association between mothers’ depression and children’s behavioral problems or emotional functioning Maternal depression was significantly related to higher levels of internalizing, externalizing, and general psychopathology and negative affect/behavior and to lower levels of positive affect/behavior, with all associations small in magnitude These associations were significantly moderated by theoretically and methodologically relevant variables, with patterns of moderation found to vary somewhat with each child outcome Results are interpreted in terms of implications for theoretical models that move beyond main effects models in order to more accurately identify which children of depressed mothers are more or less at risk for specific outcomes
2,044 citations
TL;DR: Four-dimensional covariant nonlinear theories of massive gravity are constructed which are ghost-free in the decoupling limit to all orders, and the Hamiltonian constraint is maintained at least up to and including quartic order in nonlinearities, hence excluding the possibility of the Boulware-Deser ghost up to this order.
Abstract: We construct four-dimensional covariant nonlinear theories of massive gravity which are ghost-free in the decoupling limit to all orders. These theories resum explicitly all the nonlinear terms of an effective field theory of massive gravity. We show that away from the decoupling limit the Hamiltonian constraint is maintained at least up to and including quartic order in nonlinearities, hence excluding the possibility of the Boulware-Deser ghost up to this order. We also show that the same remains true to all orders in a similar toy model.
1,909 citations
McMaster University1, University Hospital of Basel2, Autonomous University of Barcelona3, Harvard University4, Mayo Clinic5, Karolinska University Hospital6, Duke University7, Liverpool School of Tropical Medicine8, Case Western Reserve University9, University Medical Center Freiburg10, Centre for Mental Health11, Vanderbilt University12
TL;DR: It is suggested that examination of 95% confidence intervals (CIs) provides the optimal primary approach to decisions regarding imprecision and rating down the quality of evidence is required if clinical action would differ if the upper versus the lower boundary of the CI represented the truth.
1,844 citations
Seattle Children's1, National Health Service2, Beaumont Hospital3, University of Toronto4, University of Queensland5, Charles University in Prague6, Ludwig Maximilian University of Munich7, University College Dublin8, Case Western Reserve University9, Stanford University10, University of Paris11, University of Alabama at Birmingham12, Vertex Pharmaceuticals13, Queen's University Belfast14
TL;DR: Ivacaftor was associated with improvements in lung function at 2 weeks that were sustained through 48 weeks and substantial improvements were also observed in the risk of pulmonary exacerbations, patient-reported respiratory symptoms, weight, and concentration of sweat chloride.
Abstract: Background Increasing the activity of defective cystic fibrosis transmembrane conductance regulator (CFTR) protein is a potential treatment for cystic fibrosis. Methods We conducted a randomized, double-blind, placebo-controlled trial to evaluate ivacaftor (VX-770), a CFTR potentiator, in subjects 12 years of age or older with cystic fibrosis and at least one G551D-CFTR mutation. Subjects were randomly assigned to receive 150 mg of ivacaftor every 12 hours (84 subjects, of whom 83 received at least one dose) or placebo (83, of whom 78 received at least one dose) for 48 weeks. The primary end point was the estimated mean change from baseline through week 24 in the percent of predicted forced expiratory volume in 1 second (FEV1). Results The change from baseline through week 24 in the percent of predicted FEV1 was greater by 10.6 percentage points in the ivacaftor group than in the placebo group (P<0.001). Effects on pulmonary function were noted by 2 weeks, and a significant treatment effect was maintained...
1,835 citations
TL;DR: A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function, and these findings suggest potential novel therapeutic pathways for cardiovascular disease prevention.
Abstract: Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
1,829 citations
Hiroaki Aihara1, Carlos Allende Prieto2, Carlos Allende Prieto3, Deokkeun An4 +191 more•Institutions (58)
TL;DR: The first data release of SDSS-III is described in this article, which includes five-band imaging of roughly 5200 deg2 in the southern Galactic cap, bringing the total footprint of the Sloan Digital Sky Survey imaging to 14,555 deg2, or over a third of the Celestial Sphere.
Abstract: The Sloan Digital Sky Survey (SDSS) started a new phase in 2008 August, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Lyα forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg2 in the southern Galactic cap, bringing the total footprint of the SDSS imaging to 14,555 deg2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Exploration (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameter pipeline, which has better determination of metallicity for high-metallicity stars.
McMaster University1, Norwegian Institute of Public Health2, University of Basel3, University of London4, Oregon Health & Science University5, Autonomous University of Barcelona6, Bond University7, University at Buffalo8, University of Florida9, Health Canada10, Medical Research Council11, Case Western Reserve University12
TL;DR: Credibility is increased if subgroup effects are based on a small number of a priori hypotheses with a specified direction; subgroup comparisons come from within rather than between studies; tests of interaction generate low P-values; and have a biological rationale.
TL;DR: This work presents metallosupramolecular polymers that can be mended through exposure to light, which consist of telechelic, rubbery, low-molecular-mass polymers with ligand end groups that are non-covalently linked through metal-ion binding.
Abstract: Smart materials with an in-built ability to repair damage caused by normal wear and tear could prove useful in a wide range of applications. Most healable polymer-based materials so far developed require heating of the damaged area. But Burnworth et al. have now produced materials — in the form of polymer strands linked through metal complexes — that can be mended through exposure to light. The metal complexes in these materials can absorb ultraviolet light that is then converted into heat, which temporarily unlinks the polymer strands for quick and efficient defect healing. In principle, healing can take place in situ and while under load. Polymers with the ability to repair themselves after sustaining damage could extend the lifetimes of materials used in many applications1. Most approaches to healable materials require heating the damaged area2,3,4. Here we present metallosupramolecular polymers that can be mended through exposure to light. They consist of telechelic, rubbery, low-molecular-mass polymers with ligand end groups that are non-covalently linked through metal-ion binding. On exposure to ultraviolet light, the metal–ligand motifs are electronically excited and the absorbed energy is converted into heat. This causes temporary disengagement of the metal–ligand motifs and a concomitant reversible decrease in the polymers’ molecular mass and viscosity5, thereby allowing quick and efficient defect healing. Light can be applied locally to a damage site, so objects can in principle be healed under load. We anticipate that this approach to healable materials, based on supramolecular polymers and a light–heat conversion step, can be applied to a wide range of supramolecular materials that use different chemistries.
TL;DR: Evidence that leads to the proposal that during local injury, MSCs are released from their perivascular location, become activated, and establish a regenerative microenvironment by secreting bioactive molecules and regulating the local immune response is discussed.
Beckman Research Institute1, City of Hope National Medical Center2, University of Rochester3, Case Western Reserve University4, Wake Forest University5, Yale Cancer Center6, Memorial Sloan Kettering Cancer Center7, State University of New York Upstate Medical University8, Georgetown University9, University of California, Davis10, Cornell University11
TL;DR: A risk stratification schema can establish the risk of chemotherapy toxicity in older adults and Geriatric assessment variables independently predicted therisk of toxicity.
Abstract: Purpose Older adults are vulnerable to chemotherapy toxicity; however, there are limited data to identify those at risk. The goals of this study are to identify risk factors for chemotherapy toxicity in older adults and develop a risk stratification schema for chemotherapy toxicity. Patients and Methods Patients age 65 years with cancer from seven institutions completed a prechemotherapy assessment that captured sociodemographics, tumor/treatment variables, laboratory test results, and geriatric assessment variables (function, comorbidity, cognition, psychological state, social activity/support, and nutritional status). Patients were followed through the chemotherapy course to capture grade 3 (severe), grade 4 (life-threatening or disabling), and grade 5 (death) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events. Results In total, 500 patients with a mean age of 73 years (range, 65 to 91 years) with stage I to IV lung (29%), GI (27%), gynecologic (17%), breast (11%), genitourinary (10%), or other (6%) cancer joined this prospective study. Grade 3 to 5 toxicity occurred in 53% of the patients (39% grade 3, 12% grade 4, 2% grade 5). A predictive model for grade 3 to 5 toxicity was developed that consisted of geriatric assessment variables, laboratory test values, and patient, tumor, and treatment characteristics. A scoring system in which the median risk score was 7 (range, 0 to 19) and risk stratification schema (risk score: percent incidence of grade 3 to 5 toxicity) identified older adults at low (0 to 5 points; 30%), intermediate (6 to 9 points; 52%), or high risk (10 to 19 points; 83%) of chemotherapy toxicity (P .001).
McMaster University1, Mayo Clinic2, University Hospital of Basel3, Autonomous University of Barcelona4, University of South Florida5, United States Department of Veterans Affairs6, Case Western Reserve University7, Duke University8, University Medical Center Freiburg9, Oregon Health & Science University10, University at Buffalo11
TL;DR: In the GRADE approach, randomized trials start as high-quality evidence and observational studies as low- quality evidence, but both can be rated down if a body of evidence is associated with a high risk of publication bias.
TL;DR: In considering the importance of a surrogate outcome, authors should rate the importanceof the patient-important outcome for which the surrogate is a substitute and subsequently rate down the quality of evidence for indirectness of outcome.
TL;DR: The emergence of a new trend in the design of adaptive materials that involves the use of reversible chemistry to programme a response that originates at the most fundamental (molecular) level is described.
Abstract: In chemistry, some dynamic bonds can be selectively and reversibly broken and reformed in response to an environmental stimulus. This Review article discusses the incorporation of dynamic bonds, or interactions, in polymeric materials and the structural changes and macroscopic responses observed in the presence of different stimuli.
TL;DR: Decisions regarding indirectness of patients and interventions depend on an understanding of whether biological or social factors are sufficiently different that one might expect substantial differences in the magnitude of effect.
TL;DR: Various strategies that have been explored to design synthetic hydrogels with extracellular matrix-mimetic bioactive properties, such as cell adhesion, proteolytic degradation and growth factor-binding are addressed.
Abstract: This article summarizes the recent progress in the design and synthesis of hydrogels as tissue-engineering scaffolds. Hydrogels are attractive scaffolding materials owing to their highly swollen network structure, ability to encapsulate cells and bioactive molecules, and efficient mass transfer. Various polymers, including natural, synthetic and natural/synthetic hybrid polymers, have been used to make hydrogels via chemical or physical crosslinking. Recently, bioactive synthetic hydrogels have emerged as promising scaffolds because they can provide molecularly tailored biofunctions and adjustable mechanical properties, as well as an extracellular matrix-like microenvironment for cell growth and tissue formation. This article addresses various strategies that have been explored to design synthetic hydrogels with extracellular matrix-mimetic bioactive properties, such as cell adhesion, proteolytic degradation and growth factor-binding.
TL;DR: These findings show that macrophages are defended from HIV-1 infection by a mechanism that prevents an unwanted interferon response triggered by self nucleic acids, and uncover an intricate relationship between innate immune mechanisms that control response to self and to retroviral pathogens.
Abstract: Macrophages and dendritic cells have key roles in viral infections, providing virus reservoirs that frequently resist antiviral therapies and linking innate virus detection to antiviral adaptive immune responses. Human immunodeficiency virus 1 (HIV-1) fails to transduce dendritic cells and has a reduced ability to transduce macrophages, due to an as yet uncharacterized mechanism that inhibits infection by interfering with efficient synthesis of viral complementary DNA. In contrast, HIV-2 and related simian immunodeficiency viruses (SIVsm/mac) transduce myeloid cells efficiently owing to their virion-associated Vpx accessory proteins, which counteract the restrictive mechanism. Here we show that the inhibition of HIV-1 infection in macrophages involves the cellular SAM domain HD domain-containing protein 1 (SAMHD1). Vpx relieves the inhibition of lentivirus infection in macrophages by loading SAMHD1 onto the CRL4(DCAF1) E3 ubiquitin ligase, leading to highly efficient proteasome-dependent degradation of the protein. Mutations in SAMHD1 cause Aicardi-Goutieres syndrome, a disease that produces a phenotype that mimics the effects of a congenital viral infection. Failure to dispose of endogenous nucleic acid debris in Aicardi-Goutieres syndrome results in inappropriate triggering of innate immune responses via cytosolic nucleic acids sensors. Thus, our findings show that macrophages are defended from HIV-1 infection by a mechanism that prevents an unwanted interferon response triggered by self nucleic acids, and uncover an intricate relationship between innate immune mechanisms that control response to self and to retroviral pathogens.
TL;DR: The current “state of the art” of carbapenem antibiotics and their role in the antimicrobial armamentarium are summarized and the medicinal chemist is urged to continue development of these versatile and potent compounds.
Abstract: In this review, we summarize the current "state of the art" of carbapenem antibiotics and their role in our antimicrobial armamentarium. Among the β-lactams currently available, carbapenems are unique because they are relatively resistant to hydrolysis by most β-lactamases, in some cases act as "slow substrates" or inhibitors of β-lactamases, and still target penicillin binding proteins. This "value-added feature" of inhibiting β-lactamases serves as a major rationale for expansion of this class of β-lactams. We describe the initial discovery and development of the carbapenem family of β-lactams. Of the early carbapenems evaluated, thienamycin demonstrated the greatest antimicrobial activity and became the parent compound for all subsequent carbapenems. To date, more than 80 compounds with mostly improved antimicrobial properties, compared to those of thienamycin, are described in the literature. We also highlight important features of the carbapenems that are presently in clinical use: imipenem-cilastatin, meropenem, ertapenem, doripenem, panipenem-betamipron, and biapenem. In closing, we emphasize some major challenges and urge the medicinal chemist to continue development of these versatile and potent compounds, as they have served us well for more than 3 decades.
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31 Aug 2011TL;DR: In this paper, the authors evaluate the degree of convergence across method convergence for three dimensions-sales growth, net income growth, and profitability (ROI) using both Campbell and Fiske's Multi Trait, Multi Method (MTMM) and Confiratory Factor Analysis (CFA).
Abstract: Strategic management researchers have measured business economic performance (BEP) through either perceptual assessments of senior executives or secondary data sources, but few explicitly evaluate the degree of convergence across methods. In an effort to examine method convergence, we collected data on three dimensions-sales growth, net income growth, and profitability (ROI) using both methods. Although convergent and discriminant validity were achieved using Campbell and Fiske's Multi Trait, Multi Method (MTMM) and Confiratory Factor Analysis (CFA), the approaches yielded different insights. The advantages of CFA over MTMM is demonstrated with implications for strategy research.
TL;DR: In this article, a review of the application of terahertz time-domain spectroscopy to bulk and nanostructured semiconductors is presented, where the authors present a pump-probe scheme to monitor the nonequilibrium time evolution of carriers and low energy excitations with sub-ps time resolution.
Abstract: Time-resolved, pulsed terahertz spectroscopy has developed into a powerful tool to study charge carrier dynamics in semiconductors and semiconductor structures over the past decades. Covering the energy range from a few to about 100 meV, terahertz radiation is sensitive to the response of charge quasiparticles, e.g., free carriers, polarons, and excitons. The distinct spectral signatures of these different quasiparticles in the THz range allow their discrimination and characterization using pulsed THz radiation. This frequency region is also well suited for the study of phonon resonances and intraband transitions in low-dimensional systems. Moreover, using a pump-probe scheme, it is possible to monitor the nonequilibrium time evolution of carriers and low-energy excitations with sub-ps time resolution. Being an all-optical technique, terahertz time-domain spectroscopy is contact-free and noninvasive and hence suited to probe the conductivity of, particularly, nanostructured materials that are difficult or impossible to access with other methods. The latest developments in the application of terahertz time-domain spectroscopy to bulk and nanostructured semiconductors are reviewed.
Emory University1, Radiation Therapy Oncology Group2, University of Pennsylvania3, Hartford Hospital4, University of California, San Francisco5, Fox Chase Cancer Center6, Henry Ford Health System7, Washington University in St. Louis8, Medical College of Wisconsin9, Case Western Reserve University10, Primary Children's Hospital11, University of Texas MD Anderson Cancer Center12
TL;DR: Concurrent delivery of cisplatin-based chemotherapy with TRT confers a long-term survival benefit compared with the sequential delivery of these therapies.
Abstract: Background
The combination of chemotherapy with thoracic radiotherapy (TRT) compared with TRT alone has been shown to confer a survival advantage for good performance status patients with stage III non–small cell lung cancer. However, it is not known whether sequential or concurrent delivery of these therapies is the optimal combination strategy.
TL;DR: The use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6% reduced 5-year nonfatal myocardial infarctions but increased 5- year mortality, and such a strategy cannot be recommended for high-risk patients with advanced type 2 diabetes.
Abstract: A b s t r ac t Background Intensive glucose lowering has previously been shown to increase mortality among persons with advanced type 2 diabetes and a high risk of cardiovascular disease. This report describes the 5-year outcomes of a mean of 3.7 years of intensive glucose lowering on mortality and key cardiovascular events. Methods We randomly assigned participants with type 2 diabetes and cardiovascular disease or additional cardiovascular risk factors to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level of 7 to 7.9%). After termination of the intensive therapy, due to higher mortality in the intensive-therapy group, the target glycated hemoglobin level was 7 to 7.9% for all participants, who were followed until the planned end of the trial. Results Before the intensive therapy was terminated, the intensive-therapy group did not differ significantly from the standard-therapy group in the rate of the primary outcome (a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) (P = 0.13) but had more deaths from any cause (primarily cardiovascular) (hazard ratio, 1.21; 95% confidence interval [CI], 1.02 to 1.44) and fewer nonfatal myocardial infarctions (hazard ratio, 0.79; 95% CI, 0.66 to 0.95). These trends persisted during the entire follow-up period (hazard ratio for death, 1.19; 95% CI, 1.03 to 1.38; and hazard ratio for nonfatal myocardial infarction, 0.82; 95% CI, 0.70 to 0.96). After the intensive intervention was terminated, the median glycated hemoglobin level in the intensive-therapy group rose from 6.4% to 7.2%, and the use of glucose-lowering medications and rates of severe hypoglycemia and other adverse events were similar in the two groups. Conclusions As compared with standard therapy, the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6% reduced 5-year nonfatal myocardial infarctions but increased 5-year mortality. Such a strategy cannot be recommended for high-risk patients with advanced type 2 diabetes. (Funded by the National Heart, Lung and Blood Institute; ClinicalTrials.gov number, NCT00000620.)
Emory University1, University of Texas Southwestern Medical Center2, University of Utah3, Indiana University4, Stanford University5, Yale University6, Duke University7, Tufts University8, Wayne State University9, University of Texas Health Science Center at Houston10, University of Alabama at Birmingham11, University of New Mexico12, University of Iowa13, Case Western Reserve University14, University of Cincinnati15, Brown University16, Centers for Disease Control and Prevention17, National Institutes of Health18
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.
TL;DR: The inflammatory mediators and their relationship to early and late DR are reviewed, and the potential of anti-inflammatory approaches to inhibit development of different stages of the retinopathy is discussed.
McMaster University1, Norwegian Institute of Public Health2, University of Florida3, Bond University4, University at Buffalo5, Autonomous University of Barcelona6, United States Department of Veterans Affairs7, University of Basel8, Mayo Clinic9, Harvard University10, University of Freiburg11, Agency for Healthcare Research and Quality12, Oregon Health & Science University13, Case Western Reserve University14
TL;DR: Systematic review authors and guideline developers may also consider rating up quality of evidence when a dose-response gradient is present, and when all plausible confounders or biases would decrease an apparent treatment effect, or would create a spurious effect when results suggest no effect.
TL;DR: Structural, mechanistic and molecular biological studies have started to reveal how these conserved proteins can perform such diverse functions and how accessory proteins have a central role in their regulation.
Abstract: RNA helicases of the DEAD box family are present in all eukaryotic cells and in many bacteria and Archaea. These highly conserved enzymes are required for RNA metabolism from transcription to degradation and are therefore important players in gene expression. DEAD box proteins use ATP to unwind short duplex RNA in an unusual fashion and remodel RNA-protein complexes, but they can also function as ATP-dependent RNA clamps to provide nucleation centres that establish larger RNA-protein complexes. Structural, mechanistic and molecular biological studies have started to reveal how these conserved proteins can perform such diverse functions and how accessory proteins have a central role in their regulation.