Rate versus rhythm control and outcomes in patients with atrial fibrillation and chronic kidney disease: Data from the GUSTO-III Trial

Background: Atrial fi brillation (AF) and chronic kidney disease (CKD) have both beenshown to portend worse outcomes after acute myocardial infarction (MI); however, the benefi tof a rhythm control strategy in patients with CKD post-MI is unclear.Methods: We prospectively studied 985 patients with new-onset AF post-MI in theGUSTO-III trial, of whom 413 (42%) had CKD (creatinine clearance < 60 mL/min).A rhythm control strategy, defi ned as the use of an antiarrhythmic medication and/orelectrical cardioversion, was used in 346 (35%) of patients.Results: A rhythm control strategy was used in 34% of patients with CKD and 36% of patientswith no CKD. At hospital discharge, sinus rhythm was present in 487 (76%) of patients treatedwith a rate control strategy, vs. 276 (80%) in those treated with rhythm control (p = 0.20). CKDwas associated with a lower odds of sinus rhythm at discharge (unadjusted OR 0.56, 95% CI0.38–0.84, p < 0.001). However, in multivariable analyses, treatment with a rhythm controlstrategy was not associated with discharge rhythm (HR 1.068, 95% CI 0.69–1.66, p = 0.77),30-day mortality (HR 0.78, 95% CI 0.54–1.12, p = 0.18) or mortality from day 30 to 1 year(HR 1.00, 95% CI 0.59–1.69, p = 0.99). CKD status did not signifi cantly impact the relationshipbetween rhythm control and outcomes.Conclusions: Treatment with a rhythm or rate control strategy does not signifi cantly impactshort-term or long-term mortality in patients with post-MI AF, regardless of kidney disease status.Future studies to investigate the optimal management of AF in CKD patients are needed

The Anti-Sigma Factor MucA of Pseudomonas aeruginosa: Dramatic Differences of a mucA22 vs. a ΔmucA Mutant in Anaerobic Acidified Nitrite Sensitivity of Planktonic and Biofilm Bacteria in vitro and During Chronic Murine Lung Infection

Mucoid mucA22 Pseudomonas aeruginosa (PA) is an opportunistic lung pathogen of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) patients that is highly sensitive to acidified nitrite (A-NO2-). In this study, we first screened PA mutant strains for sensitivity or resistance to 20 mM A-NO2- under anaerobic conditions that represent the chronic stages of the aforementioned diseases. Mutants found to be sensitive to A-NO2- included PA0964 (pmpR, PQS biosynthesis), PA4455 (probable ABC transporter permease), katA (major catalase, KatA) and rhlR (quorum sensing regulator). In contrast, mutants lacking PA0450 (a putative phosphate transporter) and PA1505 (moaA2) were A-NO2- resistant. However, we were puzzled when we discovered that mucA22 mutant bacteria, a frequently isolated mucA allele in CF and to a lesser extent COPD, were more sensitive to A-NO2- than a truncated ΔmucA deletion (Δ157–194) mutant in planktonic and biofilm culture, as well as during a chronic murine lung infection. Subsequent transcriptional profiling of anaerobic, A-NO2--treated bacteria revealed restoration of near wild-type transcript levels of protective NO2- and nitric oxide (NO) reductase (nirS and norCB, respectively) in the ΔmucA mutant in contrast to extremely low levels in the A-NO2--sensitive mucA22 mutant. Proteins that were S-nitrosylated by NO derived from A-NO2- reduction in the sensitive mucA22 strain were those involved in anaerobic respiration (NirQ, NirS), pyruvate fermentation (UspK), global gene regulation (Vfr), the TCA cycle (succinate dehydrogenase, SdhB) and several double mutants were even more sensitive to A-NO2-. Bioinformatic-based data point to future studies designed to elucidate potential cellular binding partners for MucA and MucA22. Given that A-NO2- is a potentially viable treatment strategy to combat PA and other infections, this study offers novel developments as to how clinicians might better treat problematic PA infections in COPD and CF airway diseases

The Impact of For-Profit Hospital Status on the Care and Outcomes of Patients With Non–ST-Segment Elevation Myocardial Infarction Results From the CRUSADE Initiative

ObjectivesWe sought to determine whether for-profit status influenced hospitals’ care or outcomes among non–ST-segment elevation myocardial infarction (NSTEMI) patients.BackgroundWhile for-profit hospitals potentially have financial incentives to selectively care for younger, healthier patients, perform highly reimbursed procedures, reduce costs by limiting access to expensive medications, and encourage shorter in-patient length of stay, there are limited data available to investigate these issues objectively.MethodsUsing data from the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association guidelines) Initiative, we investigated whether for-profit status influenced hospitals’ patient case mix, care, or outcomes among 145,357 patients with NSTEMI treated between January 1, 2001, and December 31, 2005, at 532 U.S. hospitals. Impact of for-profit status on care and outcomes was analyzed overall and after adjustment for clinical and facility factors using regression modeling.ResultsPatients (n = 11,658) treated at 58 for-profit hospitals were of similar age and gender, but were more likely to be nonwhite (black, Asian, Hispanic, and other) and have health maintenance organization/private insurance, diabetes mellitus, congestive heart failure, hypertension, and renal insufficiency compared with 133,699 patients treated at 474 nonprofit hospitals. For-profit hospitals were less likely to use discharge beta-blockers, but all other treatments were similar including the use of interventional procedures (cardiac catheterization and revascularization procedures) compared with nonprofit centers. In-hospital length of stay and mortality were also similar by hospital type.ConclusionsWe found no evidence that for-profit hospitals selectively treat less sick patients, provide less evidence-based care, limit in-hospital stays, or have patients with worse acute outcomes than nonprofit centers

Autonomous Ocean Measurements in the California Current Ecosystem

Event-scale phenomena, of limited temporal duration or restricted spatial extent, often play a disproportionately large role in ecological processes occurring in the ocean water column. Nutrient and gas fluxes, upwelling and downwelling, transport of biogeochemically important elements, predator-prey interactions, and other processes may be markedly influenced by such events, which are inadequately resolved from infrequent ship surveys. The advent of autonomous instrumentation, including underwater gliders, profiling floats, surface drifters, enhanced moorings, coastal high-frequency radars, and satellite remote sensing, now provides the capability to resolve such phenomena and assess their role in structuring pelagic ecosystems. These methods are especially valuable when integrated together, and with shipboard calibration measurements and experimental programs

Three-year follow-up and event rates in the international REduction of Atherothrombosis for Continued Health Registry

To determine 3-year event rates in outpatients with vascular disease enrolled in the REduction of Atherothrombosis for Continued Health (REACH) Registry. Methods and results REACH enrolled 67 888 outpatients with atherothrombosis [ established coronary artery disease (CAD), cerebrovascutar disease, or peripheral arterial disease (PAD)], or with at least three atherothrombotic risk factors, from 44 countries . Among the 55 499 patients at baseline with symptomatic disease, 39 675 were eligible for 3-year follow-up, and 32 247 had data available (81% retention rate). Among the symptomatic patients at 3 years, 92% were taking an antithrombotic agent, 91% an anti hypertensive, and 76% were on Upid- lowering therapy. For myocardial infarction (Ml)/ stroke/vascutar death, 1 - and 3-year event rates for all patients were 4.2 and 11.0%, respectively. Event rates (MI/ stroke/vascutar death) were significantly higher for patients with symptomatic disease vs. those with risk factors only at 1 year (4.7 vs. 2.3%, P < 0.001) and at 3 years (12.0 vs. 6.0%, P < 0.001). One and 3-year rates of MI /stroke/vascular cleath/ rehospitatization were 14.4 and 28.4 %, respectively, for patients with symptomatic disease. Rehospitalization for a vascular event other than Mi/ stroke/ vascular death was common at 3 years (19.0% overall; 33.6% for PAD ; 23.0% for CAD). For patients with symptomatic vascular disease in one vascular bed vs. multiple vascular beds, 3-year event rates for MI/stroke/ vascular death/ rehospitalization were 25.5 vs. 40.5% (P < 0.001). Conclusion Despite contemporary therapy, outpatients with symptomatic atherothrombotic vascular disease experience high rates of recurrent vascular events and rehospitalizations

Comparative genomics of isolates of a pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients

Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF). During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES) from the United Kingdom and Canada representing different virulence characteristics in order to: (1) associate comparative genomics results with virulence factor variability and (2) identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40-50 kb) in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain's adaptability to varying conditions in the CF lung

About the inevitable compromise between spatial resolution and accuracy of strain measurement for bone tissue: A 3D zero-strain study

The accurate measurement of local strain is necessary to study bone mechanics and to validate micro computed tomography (μCT) based finite element (FE) models at the tissue scale. Digital volume correlation (DVC) has been used to provide a volumetric estimation of local strain in trabecular bone sample with a reasonable accuracy. However, nothing has been reported so far for μCT based analysis of cortical bone. The goal of this study was to evaluate accuracy and precision of a deformable registration method for prediction of local zero-strains in bovine cortical and trabecular bone samples. The accuracy and precision were analyzed by comparing scans virtually displaced, repeated scans without any repositioning of the sample in the scanner and repeated scans with repositioning of the samples.The analysis showed that both precision and accuracy errors decrease with increasing the size of the region analyzed, by following power laws. The main source of error was found to be the intrinsic noise of the images compared to the others investigated. The results, once extrapolated for larger regions of interest that are typically used in the literature, were in most cases better than the ones previously reported. For a nodal spacing equal to 50 voxels (498. μm), the accuracy and precision ranges were 425-692. με and 202-394. με, respectively. In conclusion, it was shown that the proposed method can be used to study the local deformation of cortical and trabecular bone loaded beyond yield, if a sufficiently high nodal spacing is used

Attentive Learning of Sequential Handwriting Movements: A Neural Network Model

Defense Advanced research Projects Agency and the Office of Naval Research (N00014-95-1-0409, N00014-92-J-1309); National Science Foundation (IRI-97-20333); National Institutes of Health (I-R29-DC02952-01)

Time lags: insights from the U.S. Long Term Ecological Research Network

Ecosystems across the United States are changing in complex ways that are difficult to predict. Coordinated long-term research and analysis are required to assess how these changes will affect a diverse array of ecosystem services. This paper is part of a series that is a product of a synthesis effort of the U.S. National Science Foundation’s Long Term Ecological Research (LTER) network. This effort revealed that each LTER site had at least one compelling scientific case study about “what their site would look like” in 50 or 100 yr. As the site results were prepared, themes emerged, and the case studies were grouped into separate papers along five themes: state change, connectivity, resilience, time lags, and cascading effects and compiled into this special issue. This paper addresses the time lags theme with five examples from diverse biomes including tundra (Arctic), coastal upwelling (California Current Ecosystem), montane forests (Coweeta), and Everglades freshwater and coastal wetlands (Florida Coastal Everglades) LTER sites. Its objective is to demonstrate the importance of different types of time lags, in different kinds of ecosystems, as drivers of ecosystem structure and function and how these can effectively be addressed with long-term studies. The concept that slow, interactive, compounded changes can have dramatic effects on ecosystem structure, function, services, and future scenarios is apparent in many systems, but they are difficult to quantify and predict. The case studies presented here illustrate the expanding scope of thinking about time lags within the LTER network and beyond. Specifically, they examine what variables are best indicators of lagged changes in arctic tundra, how progressive ocean warming can have profound effects on zooplankton and phytoplankton in waters off the California coast, how a series of species changes over many decades can affect Eastern deciduous forests, and how infrequent, extreme cold spells and storms can have enduring effects on fish populations and wetland vegetation along the Southeast coast and the Gulf of Mexico. The case studies highlight the need for a diverse set of LTER (and other research networks) sites to sort out the multiple components of time lag effects in ecosystems