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Emergency Medical Services (EMS) systems have developed protocols for prehospital activation of the cardiac catheterization laboratory for patients with suspected ST-elevation myocardial infarction (STEMI) to decrease first-medical-contact-to-balloon time (FMC2B). The rate of “false positive” prehospital activations is high. In order to decrease this rate and expedite care for patients with true STEMI, the American Heart Association (AHA; Dallas, Texas USA) developed the Mission Lifeline PreAct STEMI algorithm, which was implemented in Los Angeles County (LAC; California USA) in 2015. The hypothesis of this study was that implementation of the PreAct algorithm would increase the positive predictive value (PPV) of prehospital activation.
This is an observational pre-/post-study of the effect of the implementation of the PreAct algorithm for patients with suspected STEMI transported to one of five STEMI Receiving Centers (SRCs) within the LAC Regional System. The primary outcome was the PPV of cardiac catheterization laboratory activation for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). The secondary outcome was FMC2B.
A total of 1,877 patients were analyzed for the primary outcome in the pre-intervention period and 405 patients in the post-intervention period. There was an overall decrease in cardiac catheterization laboratory activations, from 67% in the pre-intervention period to 49% in the post-intervention period (95% CI for the difference, -14% to -22%). The overall rate of cardiac catheterization declined in post-intervention period as compared the pre-intervention period, from 34% to 30% (95% CI, for the difference -7.6% to 0.4%), but actually increased for subjects who had activation (48% versus 58%; 95% CI, 4.6%-15.0%). Implementation of the PreAct algorithm was associated with an increase in the PPV of activation for PCI or CABG from 37.9% to 48.6%. The overall odds ratio (OR) associated with the intervention was 1.4 (95% CI, 1.1-1.8). The effect of the intervention was to decrease variability between medical centers. There was no associated change in average FMC2B.
The implementation of the PreAct algorithm in the LAC EMS system was associated with an overall increase in the PPV of cardiac catheterization laboratory activation.
The smr and qacA/B genes in Staphylococcus aureus confer tolerance to antiseptics and are associated with nosocomial acquisition of infection and underlying medical conditions. Such antiseptic tolerance (AT) genes have also been reported in coagulase-negative staphylococci (CoNS) and enterococci, however, few data are available regarding their prevalence. We sought to describe the frequency of AT genes among bloodstream isolates of S. aureus, CoNS and enterococci at Texas Children’s Hospital (TCH).
Banked CoNS, S. aureus and enterococci isolated from blood cultures collected bewteen October 1, 2016, and October 1, 2017, were obtained from the TCH clinical microbiology laboratory. All isolates underwent polymerase chain reaction (PCR) assay for the qacA/B and smr genes. Medical records were reviewed for all cases.
In total, 103 CoNS, 19 Enterococcus spp, and 119 S. aureus isolates were included in the study, and 80.6% of the CoNS possessed at least 1 AT gene compared to 37% of S. aureus and 43.8% of E. faecalis isolates (P < .001). Among CoNS bloodstream isolates, the presence of either AT gene was strongly associated with nosocomial infection (P < .001). The AT genes in S. aureus were associated with nosocomial infection (P = .025) as well as the diagnosis of central-line–associated bloodstream infection (CLABSI; P = .04) and recent hospitalizations (P < .001). We found no correlation with genotypic AT in E. faecalis and any clinical variable we examined.
Antiseptic tolerance is common among bloodstream staphylococci and E. faecalis isolates at TCH. Among CoNS, the presence of AT genes is strongly correlated with nosocomial acquisition of infection, consistent with previous studies in S. aureus. These data suggest that the healthcare environment contributes to AT among staphylococci.
To describe the frequency, characteristics, and exposure associated with influenza in hospitalized patients in a Toronto hospital
Prospective data collected for consenting patients with laboratory-confirmed influenza and a retrospective review of infection control charts for roommates of cases over 3 influenza seasons
Of the 661 patients with influenza (age range: 1 week–103 years), 557 were placed on additional precautions upon admission. Of 104 with symptoms detected after admission, 57 cases were community onset and 47 were nosocomial (10 nosocomial were part of outbreaks). A total of 78 cases were detected after admission exposing 143 roommates. Among roommates tested for influenza after exposure, no roommates of community-onset cases and 2 of 16 roommates of nosocomial cases were diagnosed with influenza. Of 637 influenza-infected patients, 25% and 57% met influenza-like illness definitions from the Public Health Agency of Canada (PHAC) and Centers for Disease Control and Prevention (CDC), respectively, and 70.3% met the Provincial Infectious Diseases Advisory Committee (PIDAC) febrile respiratory illness definition. Among the 56 patients with community-onset influenza detected after admission, only 13%, 23%, and 34%, met PHAC, CDC, and PIDAC classifications, respectively.
In a setting with extensive screening and testing for influenza, 1 in 6 patients with influenza was not diagnosed until patients and healthcare workers had been exposed for >24 hours. Only 30% of patients with community-onset influenza detected after admission met the Ontario definition intended to identify cases, hampering efforts to prevent patient and healthcare worker exposures and reinforcing the need for prevention through vaccination.
Not only is depression associated with increased inflammation but inflammation is a risk factor for the genesis of depression. Many of the environmental risk factors for depression are transduced through inflammatory signaling. Anti-inflammatory agents show promise for the management of depression in preclinical, epidemiological, and early clinical studies. This opens the door to the potential for anti-inflammatory agents to treat and prevent depression. There are no evidence-based pharmacotherapies for depression prevention.
ASPREE-D, aspirin in the prevention of depression in the elderly, is a sub study of ASPREE, which explores the potential of aspirin to prevent a range of inflammation related disorders in the elderly. With a sample size of 19,114, and a duration of 5 years, this placebo controlled study will be one of the largest randomized controlled trials in psychiatry and will provide definitive evidence on the ability of aspirin to prevent depression.
This paper presents the rationale for the study and presents a summary of the study design.
ASPREE-D may not only define novel therapy but will provide mechanistic proof of concept of the role of inflammation in depression.
Supplemented protein or specific amino acids (AA) are proposed to help animals combat infection and inflammation. The current study investigates whole-body and splanchnic tissue metabolism in response to a lipopolysaccharide (LPS) challenge with or without a supplement of six AA (cysteine, glutamine, methionine, proline, serine and threonine). Eight sheep were surgically prepared with vascular catheters across the gut and liver. On two occasions, four sheep were infused through the jugular vein for 20 h with either saline or LPS from Escherichia coli (2 ng/kg body weight per min) in a random order, plus saline infused into the mesenteric vein; the other four sheep were treated with saline or LPS plus saline or six AA infused via the jugular vein into the mesenteric vein. Whole-body AA irreversible loss rate (ILR) and tissue protein metabolism were monitored by infusion of [ring-2H2]phenylalanine. LPS increased (P<0·001) ILR (+17 %), total plasma protein synthesis (+14 %) and lymphocyte protein synthesis (+386 %) but decreased albumin synthesis (−53 %, P=0·001), with no effect of AA infusion. Absorption of dietary AA was not reduced by LPS, except for glutamine. LPS increased the hepatic removal of leucine, lysine, glutamine and proline. Absolute hepatic extraction of supplemented AA increased, but, except for glutamine, this was less than the amount infused. This increased net appearance across the splanchnic bed restored arterial concentrations of five AA to, or above, values for the saline-infused period. Infusion of key AA does not appear to alter the acute period of endotoxaemic response, but it may have benefits for the chronic or recovery phases.
The liquidity premium on corporate bonds has been high on the agenda of Solvency regulators owing to its potential relationship to an additional discount factor on long-dated insurance liabilities. We analyse components of the credit spread as a function of standard bond characteristics during 2003–2014 on a daily basis by regression analyses, after introducing a new liquidity proxy. We derive daily distributions of illiquidity contributions to the credit spread at the individual bond level and find that liquidity premia were close to zero just before the financial crisis. We observe the time-varying nature of liquidity premia as well as a widening in the daily distribution in the years after the credit crunch. We find evidence to support higher liquidity premia, on average, on bonds of lower credit quality. The evolution of model parameters is economically intuitive and brings additional insight into investors’ behaviour. The frequent and bond-level estimation of liquidity premia, combined with few data restrictions makes the approach suitable for ALM modelling, especially when future work is directed towards arriving at forward-looking estimates at both the aggregate and bond-specific level.
The implementation of hedging strategies for variable annuity products requires the calculation of market risk sensitivities (or “Greeks”). The complex, path-dependent nature of these products means that these sensitivities are typically estimated by Monte Carlo methods. Standard market practice is to use a “bump and revalue” method in which sensitivities are approximated by finite differences. As well as requiring multiple valuations of the product, this approach is often unreliable for higher-order Greeks, such as gamma, and alternative pathwise (PW) and likelihood-ratio estimators should be preferred. This paper considers a stylized guaranteed minimum withdrawal benefit product in which the reference equity index follows a Heston stochastic volatility model in a stochastic interest rate environment. The complete set of first-order sensitivities with respect to index value, volatility and interest rate and the most important second-order sensitivities are calculated using PW, likelihood-ratio and mixed methods. It is observed that the PW method delivers the best estimates of first-order sensitivities while mixed estimation methods deliver considerably more accurate estimates of second-order sensitivities; moreover there are significant computational gains involved in using PW and mixed estimators rather than simple BnR estimators when many Greeks have to be calculated.
The presence or absence of dwarf galaxies with Mr' > -14 in low-density volumes correlates with dark matter halos and how they affect galaxy formation. We are conducting a redshifted Hα imaging survey for dwarf galaxies with Mr' > -13 in the heart of the well-defined voids FN2 and FN8 using the KPNO 4m Mayall telescope and Mosaic Imager. These data have furnished over 600 strong candidates in a four square degree area. Follow-up spectra finding none of these candidates to be within the void volumes will constrain the dwarf population there to be 2 to 8% of the cosmic mean. Conversely, finding even one Hα dwarf in the void heart will challenge several otherwise successful theories of large-scale structure formation.
Burnout symptoms, which are characterized by exhaustion, cynicism, and a reduced sense of professional efficacy, may deleteriously affect cognitive function in military personnel. A total of 32 U.S. Military Special Operations personnel enrolled in Survival School completed measures of trauma history, dissociation, and burnout before training. They then completed the Groton Maze Learning Test (GMLT), a neuropsychological measure of integrative visuospatial executive function during three field-based phases of Survival School—enemy evasion, captivity/interrogation, and escape/release from captivity. Lower pre-training perceptions of professional efficacy were associated with reduced executive function during all of the field-based phases of Survival School, even after adjustment for years of education, cynicism, and baseline GMLT scores. Magnitudes of decrements in executive function in Marines with low efficacy relative to those with high efficacy increased as training progressed and ranged from .58 during enemy evasion to .99 during escape/release from captivity. Pre-training perceptions of burnout may predict visuospatial executive function during naturalistic training-related stress in military personnel. Assessment of burnout symptoms, particularly perceptions of professional efficacy, may help identify military personnel at risk for stress-related executive dysfunction. (JINS, 2011, 17, 494–501)
To identify predictors of increasing waist circumference (WC) over a 5-year period in a contemporary population of Australian adults.
Longitudinal national cohort of adults participating in the Australian Diabetes, Obesity and Lifestyle Study (AusDiab).
Australian adults in 2000 and 2005.
A total of 2521 men and 2726 women aged ≥25 years at baseline who participated in AusDiab and provided anthropometric measurements at baseline (1999–2000) and follow-up (2005).
A ≥5 % increase of baseline WC occurred in 27 % of men and 38 % of women over the 5-year period. In the multivariate analysis of the total population, there was a higher risk of ≥5 % gain in baseline WC in women, younger people, people with a lower baseline WC, people who never married compared with married/de facto, current smokers compared with never smokers, people with a poorer diet quality and people with a low energy intake. However, there was no significant association with many expected predictors of waist gain such as physical activity. There were some associations between other lifestyle factors and change of WC by sex, age, level of education and across WC categories, but the associations differed across these groups.
A ≥5 % increase of baseline WC occurred in a significant proportion of men and women over the 5-year period. Of the behavioural factors, poor diet quality was the key predictor of the ≥5 % increase of baseline WC in this cohort. The findings highlight the need to understand better the causal role of lifestyle in regard to increasing WC over time.
To analyse changes in the distribution of BMI in Australia between 1980 and 2000.
Data were from the 1980, 1983 and 1989 National Heart Foundation Risk Factor Prevalence Study, the 1995 National Nutrition Survey and the 1999/2000 Australian Diabetes, Obesity and Lifestyle Study. Survey participants were aged 25–64 years and resident in Australian capital cities. BMI was calculated as weight divided by height squared (kg/m2), where weight and height were measured using standard procedures.
Mean BMI was higher in 2000 than 1980 in all sex and age groups. The age-adjusted increase was 1·4 kg/m2 in men and 2·1 kg/m2 in women. The BMI distribution shifted rightwards for all sex and age groups and became increasingly right-skewed. The change between 1980 and 2000 ranged from a decrease of 0·04 kg/m2 at the lower end of the distribution for men aged 25–34 years to an increase of 7·4 kg/m2 at the higher end for women aged 55–64 years. While the prevalence of obesity (BMI ≥ 30 kg/m2) doubled, the prevalence of obesity class III (BMI ≥ 40 kg/m2) increased fourfold.
BMI in urban Australian adults has increased and its distribution has become increasingly right-skewed. This has resulted in a large increase in the prevalence of obesity, particularly the more severe levels of obesity. It will be important to monitor changes in the different classes of obesity and the extent to which obesity interventions both shift the BMI distribution leftwards and decrease the skew of the distribution.
Previously we have examined the effects of diets deficient in folic acid ( − F) or folate deficient with low methionine and choline ( − F LM LC) on the relative abundance of soluble proteins in the liver of the pregnant rat. In the present study we report the corresponding changes in the fetal liver at day 21 of gestation. The abundance of eighteen proteins increased when dams were fed the − F diet. When dams were fed the − F LM LC diet, thirty-three proteins increased and eight decreased. Many of the differentially abundant proteins in the fetal liver could be classified into the same functional groups as those previously identified in the maternal liver, namely protein synthesis, metabolism, lipid metabolism and proteins associated with the cytoskeleton and endoplasmic reticulum. The pattern was consistent with reduced cell proliferation in the − F LM LC group but not in the − F group. Metabolic enzymes associated with lipid metabolism changed in both the − F and − F LM LC groups. The mRNA for carnitine palmitoyl transferase were up-regulated and CD36 (fatty acid translocase) down-regulated in the − F group, suggesting increased mitochondrial oxidation of fatty acids as an indirect response to altered maternal lipid metabolism. In the − F LM LC group the mRNA for acetyl CoA carboxylase was down-regulated, suggesting reduced fatty acid synthesis. The mRNA for transcriptional regulators including PPARα and sterol response element-binding protein-1c were unchanged. These results suggest that an adequate supply of folic acid and the related methyl donors may benefit fetal development directly by improving lipid metabolism in fetal as well as maternal tissues.
Microstructured semiconductor neutron detectors have superior efficiency performance over thin-film coated planar semiconductor detectors. The microstructured detectors have patterns deeply etched into the semiconductor substrates subsequently backfilled with neutron reactive materials. The detectors operate as pn junction diodes. Two variations of the diodes have been fabricated, which either have a rectifying pn junction selectively formed around the etched microstructures or have pn junctions conformally diffused inside the microstructures. The devices with the pn junctions formed in the perforations have lower leakage currents and better signal formation than the devices with selective pn junctions around the etched patterns. Further, pulse height spectra from conformally diffused detectors have the main features predicted by theoretical models, whereas pulse height spectra from the selectively diffused detectors generally do not show these features. The improved performance of the conformal devices is attributed to stronger and more uniform electric fields in the detector active region. Also, system noise, which is directly related to leakage current, has been dramatically reduced as a result of the conformal diffusion fabrication technique. A sinusoidal patterned device with 100 μm deep perforations backfilled with 6LiF was determined to have 11.9 ± 0.078% intrinsic detection efficiency for 0.0253 eV neutrons, as calibrated with thin-film planar semiconductor devices and a 3He proportional counter.
The importance of folic acid and the methionine cycle in fetal development is well recognised even though the mechanism has not been established. Since the cycle is active in the maternal liver, poor folate status may modify hepatic metabolism. Pregnant rats were fed diets deficient in folic acid (–F) or in three key methyl donors, folic acid, choline and methionine (–FLMLC) and the maternal liver was analysed on day 21 of gestation. Two-dimensional gel electrophoresis of soluble proteins identified differentially abundant proteins, which could be allocated into nine functional groups. Five involved in metabolic processes, namely, folate/methionine cycle, tyrosine metabolism, protein metabolism, energy metabolism and lipid metabolism, and three in cellular processes, namely, endoplasmic reticulum function, bile production and antioxidant defence. The mRNA for sterol regulatory element-binding protein-1c and acetyl-CoA carboxylase-1 (fatty acid synthesis) were decreased by both –F and –FLMLC diets. The mRNA for PPARα and PPARγ and carnitine palmitoyl transferase (fatty acid oxidation) were increased in the animals fed the –FLMLC diets. Changes in the abundance of proteins associated with intracellular lipid transport suggest that folate deficiency interferes with lipid export. Reduced fatty acid synthesis appeared to prevent steatosis in animals fed the –F diet. Even with increased oxidation, TAG concentrations were approximately three-fold higher in animals fed the –FLMLC diet and were associated with an increase in the relative abundance of proteins associated with oxidative stress. Fetal development may be indirectly affected by these changes in hepatic lipid metabolism.