Hospital Profiling of the Cesarean Delivery Procedure for the State of Georgia, 2012

Approximately 35.1% of live births for the state of Georgia were delivered by the cesarean delivery procedure with significant variation among hospitals. The purpose of this research was to develop a population-based hospital profiling methodology for study of the cesarean delivery procedure. This was a retrospective, observational design, using a 2012 linked dataset that included maternity deliveries from all nonfederal hospitals. The research was guided by Robson 10 Group Classification System, propensity score methodologies, and ethical precepts, for the development of hospital profiles and the study of variations in the cesarean delivery procedure. Key research questions aimed to determine whether hospital profiling methodologies differed according to risk adjustment methods and statistical techniques. Propensity score matching with stratification methods aimed to determine whether there were differences in patient treatment effects on the cesarean delivery outcome. Findings suggested there was a significant difference in hospital ranks and model effects according to the statistical technique and the risk adjustment methods applied. Propensity score matching with stratification demonstrated an increased risk of the cesarean delivery procedure across strata, with the majority of high risk patients situated in the 90th percentile ranges and questionable utilization practice among other strata. Applying profiling methodologies at the facility and population level could advance statewide quality improvement programs for the timely reduction in the variation of inappropriate utilization of the cesarean delivery procedure

Dynamics of a long-lived magmatic system as indicated by variations in amphibole composition and textures in dacites erupted over 11 M.y. at the Aucanquilcha Volcanic Cluster, Central Andes, Chile

The Aucanquilcha Volcanic Cluster (AVC) is the erupted part of a magmatic system with a complex and long-lived history. The AVC lies at 21°S in the high Andes and is built on thick continental crust. The thick crust in the area combined with the prolonged magmatic activity make it an excellent natural laboratory for examining long-term evolution of a continental arc volcanic system. The eruptive products deposited over the last 11 million years of volcanic activity preserve snapshots of the developing, dominantly dacitic, magmatic system and gives indications of the processes occurring at depth. In this study, the textural and compositional diversity of amphiboles from selected dacites inform the development of the intensive magmatic parameters including pressure, temperature and volatile content, during the protracted magmatism observed at the AVC. There are 4 dominant amphibole compositions erupted at the AVC, higher aluminum magnesiohastingsite, pargasite, and tschermakite and the relatively low aluminum magnesiohornblende, using the nomenclature of Leake et al., 1997. Amphiboles in early erupted dacites (11-8 Ma) occur in two compositionally distinct aluminum populations and have diverse textures. During voluminous dacite volcanism between 6 and 2 Ma, amphiboles are most strongly compositionally zoned, and while still displaying textural diversity, some equilibrium textures common in the early and late stages are rare. In the youngest stage (1-0.24 Ma), amphiboles in many dacites have two compositional populations distinguished by alunimum; equilibrium crystals with thin or no reaction rim are most common in the amphiboles from this stage. Changes in Cl, F and S and stable isotopes of the system were used as indicators of the evolution of the magmatic system. Fluorine increases in amphiboles over the 11 million year magmatic history independent of amphibole composition, implying a system-wide increase in F. Sulfur and chlorine in amphiboles correlate well with aluminum in amphibole: low aluminum amphiboles have low S (up to 40 ppm), whereas higher aluminum amphiboles had sulfur contents from 70-160 ppm. Amphiboles with lower aluminum have lower Cl contents than amphiboles with higher aluminum. Coupled amphibole geothermometry and geobarometry are utilized in this study to investigate pressure and temperature of the magmas at the AVC. Amphiboles from the early group are consistent with eruption of dacite from discrete magma batches: some residing at shallow levels of ~1-2 kbar and ~700-800 °C and some deeper at ~4-6.5 kbar and ~750-850 °C. It is interpreted that with time, the dacitic magma reservoir becomes integrated at relatively shallow levels (1.8-3.5 kbar and ~800-900°C). In waning, increasingly silicic stage of volcanism (~1-0.24 Ma), dacite magma is erupted from a shallow and cooler system of ~0.5-1.8kbar and ~700-800 °C

Maternal Obesity in Pregnancy Developmentally Programs Adipose Tissue Inflammation in Young, Lean Male Mice Offspring.

Obesity during pregnancy has a long-term effect on the health of the offspring including risk of developing the metabolic syndrome. Using a mouse model of maternal diet-induced obesity, we employed a genome-wide approach to investigate the microRNA (miRNA) and miRNA transcription profile in adipose tissue to understand mechanisms through which this occurs. Male offspring of diet-induced obese mothers, fed a control diet from weaning, showed no differences in body weight or adiposity at 8 weeks of age. However, offspring from the obese dams had up-regulated cytokine (Tnfα; P < .05) and chemokine (Ccl2 and Ccl7; P < .05) signaling in their adipose tissue. This was accompanied by reduced expression of miR-706, which we showed can directly regulate translation of the inflammatory proteins IL-33 (41% up-regulated; P < .05) and calcium/calmodulin-dependent protein kinase 1D (30% up-regulated; P < .01). We conclude that exposure to obesity during development primes an inflammatory environment in adipose tissue that is independent of offspring adiposity. Programming of adipose tissue miRNAs that regulate expression of inflammatory signaling molecules may be a contributing mechanism.This work was supported by Funding sources: National Council for the Improvement of Higher Education (CAPES - Brazil - BEX 10 594/13–2); National Counsel of Technological and Scientific Development (CNPq – Brazil – PDE/204416/ 2014–0); Medical Research Council (MC UU 12012/4 and MC UU12012/5), BBSRC (BB/M001636/1) and the Wellcome Trust (089940/Z/09/Z).This is the final version of the article. It first appeared from the Endocrine Society via http://dx.doi.org/10.1210/en.2016-131

Mapping regional implementation of 'Making Every Contact Count': mixed methods 2 evaluation of implementation stage, strategies, barriers and facilitators of implementation

Background: The Making Every Contact Count (MECC) programme provides training and materials to support public-facing workers to encourage health-promoting behaviour change by using the day-to-day interactions between organisations and individuals. This project aimed to analyse MECC implementation through a comparative analysis of implementation stage, strategies used for implementation and enablers/barriers of the implementation process within a region in England-the North East and North Cumbria (NENC).Methods: A mixed-methods process evaluation was conducted applying normalisation process theory and theoretical domains framework. MECC programme documents were reviewed and mapped against specific criteria (eg, implementation strategies). An online mapping survey was conducted to establish current implementation/delivery of MECC within NENC settings (eg, local government, healthcare and voluntary community sector). Qualitative research, using individual interviews and group discussions, was conducted to establish further understanding of MECC implementation.Results: Our findings were informed by reviewing documents (n=5), surveying participants (n=34), interviews (n=18) and group discussions (n=48). Overall, the implementation of MECC within the region was at an early stage, with training mostly delivered between, rather than within, organisations. Qualitative findings highlighted factors that influence stakeholders to implement MECC (eg, organisational goals that were facilitated by MECC implementation, including the prevention agenda), supported resources that facilitate the implementation of MECC (eg, logic models) and enabling factors that promote MECC sustainability across the region (eg, buy-in from leadership and management).Conclusions: The NENC MECC programme is built around regional leadership that supports the implementation process. This process evaluation identified key influences of MECC implementation across the region. We discuss evidence-based recommendation for policy and practice that can be taken forward to develop targeted strategies to support future MECC implementation. For example, a co-ordinated infrastructure and strategy is needed to combat delivery and implementation issues identified

Troponin in Acute Chest Pain to Risk Stratify and Guide Effective Use of Computed Tomography Coronary Angiography (TARGET-CTCA): A Randomised Controlled Trial

BACKGROUND: The majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death. METHODS: TARGET-CTCA is a multicentre prospective randomised open label with blinded endpoint parallel group event driven trial. After myocardial infarction and clear alternative diagnoses have been ruled out, participants with intermediate cardiac troponin concentrations (5 ng/L to 99th centile upper reference limit) will be randomised 1:1 to outpatient CTCA plus standard of care or standard of care alone. The primary endpoint is myocardial infarction or cardiac death. Secondary endpoints include clinical, patient-centred, process and cost-effectiveness. Recruitment of 2270 patients will give 90% power with a two-sided P value of 0.05 to detect a 40% relative risk reduction in the primary endpoint. Follow-up will continue until 97 primary outcome events have been accrued in the standard care arm with an estimated median follow-up of 36 months. DISCUSSION: This randomised controlled trial will determine whether high-sensitivity cardiac troponin-guided CTCA can improve outcomes and reduce subsequent major adverse cardiac events in patients presenting to the emergency department who do not have myocardial infarction

Troponin in Acute chest pain to Risk stratify and Guide EffecTive use of Computed Tomography Coronary Angiography (TARGET-CTCA):A randomised controlled trial

Background: The majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death. Methods: TARGET-CTCA is a multicentre prospective randomised open label with blinded endpoint parallel group event driven trial. After myocardial infarction and clear alternative diagnoses have been ruled out, participants with intermediate cardiac troponin concentrations (5 ng/L to 99th centile upper reference limit) will be randomised 1:1 to outpatient CTCA plus standard of care or standard of care alone. The primary endpoint is myocardial infarction or cardiac death. Secondary endpoints include clinical, patient-centred, process and cost-effectiveness. Recruitment of 2270 patients will give 90% power with a two-sided P value of 0.05 to detect a 40% relative risk reduction in the primary endpoint. Follow-up will continue until 97 primary outcome events have been accrued in the standard care arm with an estimated median follow-up of 36 months. Discussion: This randomised controlled trial will determine whether high-sensitivity cardiac troponin-guided CTCA can improve outcomes and reduce subsequent major adverse cardiac events in patients presenting to the emergency department who do not have myocardial infarction. Trial registration: ClinicalTrials.gov Identifier: NCT03952351. Registered on May 16, 2019

Sedimentary Environment Influences the Effect of an Infaunal Suspension Feeding Bivalve on Estuarine Ecosystem Function

The suspension feeding bivalve Austrovenus stutchburyi is a key species on intertidal sandflats in New Zealand, affecting the appearance and functioning of these systems, but is susceptible to several environmental stressors including sedimentation. Previous studies into the effect of this species on ecosystem function have been restricted in space and time, limiting our ability to infer the effect of habitat change on functioning. We examined the effect of Austrovenus on benthic primary production and nutrient dynamics at two sites, one sandy, the other composed of muddy-sand to determine whether sedimentary environment alters this key species' role. At each site we established large (16 m2) plots of two types, Austrovenus addition and removal. In winter and summer we deployed light and dark benthic chambers to quantify oxygen and nutrient fluxes and measured sediment denitrification enzyme activity to assess denitrification potential. Rates of gross primary production (GPP) and ammonium uptake were significantly increased when Austrovenus was added, relative to removed, at the sandy site (GPP, 1.5 times greater in winter and summer; ammonium uptake, 8 times greater in summer; 3-factor analysis of variance (ANOVA), p<0.05). Denitrification potential was also elevated in Austrovenus addition plots at the sandy site in summer (by 1.6 times, p<0.1). In contrast, there was no effect of Austrovenus treatment on any of these variables at the muddy-sand site, and overall rates tended to be lower at the muddy-sand site, relative to the sandy site (e.g. GPP was 2.1 to 3.4 times lower in winter and summer, respectively, p<0.001). Our results suggest that the positive effects of Austrovenus on system productivity and denitrification potential is limited at a muddy-sand site compared to a sandy site, and reveal the importance of considering sedimentary environment when examining the effect of key species on ecosystem function

A Mycobacterium leprae Hsp65 Mutant as a Candidate for Mitigating Lupus Aggravation in Mice

Hsp60 is an abundant and highly conserved family of intracellular molecules. Increased levels of this family of proteins have been observed in the extracellular compartment in chronic inflammation. Administration of M. leprae Hsp65 [WT] in [NZBxNZW]F1 mice accelerates the Systemic Lupus Erythematosus [SLE] progression whereas the point mutated K409A Hsp65 protein delays the disease. Here, the biological effects of M. leprae Hsp65 Leader pep and K409A pep synthetic peptides, which cover residues 352–371, are presented. Peptides had immunomodulatory effects similar to that observed with their respective proteins on survival and the combined administration of K409A+Leader pep or K409A pep+WT showed that the mutant forms were able to inhibit the deleterious effect of WT on mortality, indicating the neutralizing potential of the mutant molecules in SLE progression. Molecular modeling showed that replacing Lysine by Alanine affects the electrostatic potential of the 352–371 region. The number of interactions observed for WT is much higher than for Hsp65 K409A and mouse Hsp60. The immunomodulatory effects of the point-mutated protein and peptide occurred regardless of the catalytic activity. These findings may be related to the lack of effect on survival when F1 mice were inoculated with Hsp60 or K409A pep. Our findings indicate the use of point-mutated Hsp65 molecules, such as the K409A protein and its corresponding peptide, that may minimize or delay the onset of SLE, representing a new approach to the treatment of autoimmune diseases

Administration of M. leprae Hsp65 Interferes with the Murine Lupus Progression

The heat shock protein [Hsp] family guides several steps during protein synthesis, are abundant in prokaryotic and eukaryotic cells, and are highly conserved during evolution. The Hsp60 family is involved in assembly and transport of proteins, and is expressed at very high levels during autoimmunity or autoinflammatory phenomena. Here, the pathophysiological role of the wild type [WT] and the point mutated K409A recombinant Hsp65 of M. leprae in an animal model of Systemic Lupus Erythematosus [SLE] was evaluated in vivo using the genetically homogeneous [NZBxNZW]F1 mice. Anti-DNA and anti-Hsp65 antibodies responsiveness was individually measured during the animal's life span, and the mean survival time [MST] was determined. The treatment with WT abbreviates the MST in 46%, when compared to non-treated mice [p<0.001]. An increase in the IgG2a/IgG1 anti-DNA antibodies ratio was also observed in animals injected with the WT Hsp65. Incubation of BALB/c macrophages with F1 serum from WT treated mice resulted in acute cell necrosis; treatment of these cells with serum from K409A treated mice did not cause any toxic effect. Moreover, the involvement of WT correlates with age and is dose-dependent. Our data suggest that Hsp65 may be a central molecule intervening in the progression of the SLE, and that the point mutated K409A recombinant immunogenic molecule, that counteracts the deleterious effect of WT, may act mitigating and delaying the development of SLE in treated mice. This study gives new insights into the general biological role of Hsp and the significant impact of environmental factors during the pathogenesis of this autoimmune process