Myocardial dysfunction is a well-documented outcome of extended periods of high cardiac output. Whether similar effects occur during firefighting, an occupation characterized by repeated periods of ...work compounded by dehydration and heat stress, is uncertain.
To investigate the independent and combined effects of moderate heat stress and dehydration on indicators of myocardial performance following intermittent, submaximal treadmill exercise while wearing personal protective equipment (PPE).
Twelve aerobically fit young men (age 21.5±2.6 years; maximal oxygen uptake VO2max 60.3±4.4ml kg(-1) min(-1)) performed intermittent treadmill walking exercise consisting of three 20min bouts at an intensity of ~40% VO2max separated by two periods of rest in four different conditions in random order: (i) no heat stress-euhydrated, (ii) heat stress-euhydrated (heat stress created by wearing PPE, (iii) no heat stress-dehydrated and (iv) heat stress-dehydrated. We measured core temperature by a telemetric gastrointestinal pill. We determined cardiac variables by standard echocardiographic techniques immediately before and ~30min after exercise.
We recorded no significant changes in markers of systolic (ejection fraction, shortening fraction, tissue Doppler-S) or diastolic (mitral peak E velocity, tissue Doppler-E' and E/E') function following exercise in any of the four conditions.
In this model of exercise designed to mimic the work, heat stress and dehydration associated with firefighting activities, we observed no negative effects on myocardial inotropic or lusitropic function.
X-ray absorption spectroscopy (XAS) has been used to define the local chemical environments of Tc and its proposed chemical analogue Re in precipitates of mackinawite (tetragonal FeS) and its ...oxidation products. Pertechnetate, TcO
4
−, is reduced to Tc(IV) on coprecipitation with FeS, while Tc(IV) undergoes no redox change. A TcS
2-like phase is formed in both cases. On oxidation of the host lattice, Tc remains in oxidation state IV and forms a phase similar to TcO
2. Perrhenate, ReO
4
−, behaves in a similar way to TcO
4
− on coprecipitation although there is evidence that Re–S–Fe phases form. On reoxidation, the host FeS forms goethite and the Re may occupy channels in the goethite structure. Re(IV) is anomalous in that it forms a ReO
2−like phase on coprecipitation with FeS, perhaps due to hydrolysis before precipitation of the FeS. These results suggest that the Tc/Re analogy is only partially sound and the elements are not identical. The failure of Tc held in FeS to reform TcO
4
− on reoxidation of the FeS suggests that its mobility may be substantially reduced by natural anoxic environments and coprecipitation might be considered as a method of reducing Tc waste discharges.
Purpose
: To determine the time course and incidence of late complications from radiation therapy in patients treated with radiation for FIGO Stage IB carcinoma of the uterine cervix, and to evaluate ...patient and tumor factors associated with an increased probability of treatment complications.
Methods and Materials
: The medical records of 1784 patients with FIGO Stage IB cervical carcinoma who were treated with initial radiation therapy between 1960 and 1989 were retrospectively reviewed. Follow-up was obtained from clinic visits and correspondence with patients and their physicians. Treatment complications were graded retrospectively. Complication rates were calculated actuarially; patients who died of disease or intercurrent illness without experiencing a major complication were censored at the time of death. There were 1241, 924, 548, and 274 patients followed fro more than 5, 10, 15, and 20 years, respectively.
Results
: Of patients treated for Stage IB cervical carcinoma, 7.7% and 9.3% had experienced major (≥Grade 3) complications at 3 and 5 years, respectively. After 5 years, there was a small but continuous risk of approximately 0.34% per year, resulting in an overall actualrial risk of having had major complications of 14.4% at 20 years. The risk of developing major urninary tract complications was approximately 0.7% per year for the first 3 years of follow-up, decreasing to about 0.25% per year for at least 25 years. In contrast, the risk of developing rectal complications was about 1% per year during the first 2 years, with a subsequent sharp decline to about 0.06% per year between Years 2 and 25. The risk of fistula formation was approximately doubled in the 234 patients who underwent adjuvant extrafascial hystectomy (5.3 vs. 2.6% at 20 years;
p = 0.04) and in the 111 patients who had pretreatment laparotomy (5.2 vs. 2.9%;
p = 0.007). The risk of developing small bowel obstruction was increased in patients who underwent pretreatment laparotomy (14.5 vs. 3.7% at 10 years;
p < 0.0001) and in patients who weighed <120 pounds (8.2 vs. 3.6%;
p = 0.004), but was not increased in patients who underwent adjuvant hysterectomy. A signicantly greater risk of gastrointestinal complications was observed in black and non-Hispanic white patients than in Hispanic women (
p = 0.01), even though there was no difference in the rate of developing urinary tract complications (
p = 1.0). There was no correlation between the actuarial risk of developing major complications and the patients' age at the time of treatment, but not the cumulative risk was greater for patients who were treated at a young age because these patients were more likely to survive to be exposed to a very long period of risk.
Conclusion
: Using techniques described by Fletcher and Delclos, the risk of major complications from aggressive irradiation for Stage IB carcinoma of the cervix is low and does not warrant compromises in the intensity of treatment that might decrease the high cure rates achieved in such patients. The long time course of some late complications also suggests that continued surveillance of survivors, by physicians experienced in the diagnosis and management of the sequelae of the curative radiation treatment of cervical center, is important.
Iron deficiency, in the absence of anemia, is common in patients with idiopathic and heritable pulmonary arterial hypertension (PAH) and is associated with a worse clinical outcome. Oral iron ...absorption may be impeded by elevated circulating hepcidin concentrations. The safety and benefit of parenteral iron replacement in this patient population is unclear.
To evaluate the safety and efficacy of parenteral iron replacement in PAH.
In two randomized, double-blind, placebo-controlled 12-week crossover studies, 39 patients in Europe received a single infusion of ferric carboxymaltose (Ferinject) (1,000 mg or 15 mg/kg if weight <66.7 kg) or saline as placebo, and 17 patients in China received iron dextran (Cosmofer) (20 mg iron/kg body weight) or saline placebo. All patients had idiopathic or heritable PAH and iron deficiency at entry as defined by a serum ferritin <37 μg/L or iron <10.3 μmol/L or transferrin saturations <16.4%.
Both iron treatments were well tolerated and improved iron status. Analyzed separately and combined, there was no effect on any measure of exercise capacity (using cardiopulmonary exercise testing or 6-minute walk test) or cardiopulmonary hemodynamics, as assessed by right heart catheterization, cardiac magnetic resonance, or plasma NT-proBNP (N-terminal-pro hormone brain natriuretic peptide) at 12 weeks.
Iron repletion by administration of a slow-release iron preparation as a single infusion to patients with PAH with iron deficiency without overt anemia was well tolerated but provided no significant clinical benefit at 12 weeks. Clinical trial registered with ClinicalTrials.gov (NCT01447628).
Idiopathic and heritable pulmonary arterial hypertension (PAH) are rare but comprise a genetically heterogeneous patient group. RNA sequencing linked to the underlying genetic architecture can be ...used to better understand the underlying pathology by identifying key signaling pathways and stratify patients more robustly according to clinical risk.
To use a three-stage design of RNA discovery, RNA validation and model construction, and model validation to define a set of PAH-associated RNAs and a single summarizing RNA model score. To define genes most likely to be involved in disease development, we performed Mendelian randomization (MR) analysis.
RNA sequencing was performed on whole-blood samples from 359 patients with idiopathic, heritable, and drug-induced PAH and 72 age- and sex-matched healthy volunteers. The score was evaluated against disease severity markers including survival analysis using all-cause mortality from diagnosis. MR used known expression quantitative trait loci and summary statistics from a PAH genome-wide association study.
We identified 507 genes with differential RNA expression in patients with PAH compared with control subjects. A model of 25 RNAs distinguished PAH with 87% accuracy (area under the curve 95% confidence interval: 0.791-0.945) in model validation. The RNA model score was associated with disease severity and long-term survival (
= 4.66 × 10
) in PAH. MR detected an association between SMAD5 levels and PAH disease susceptibility (odds ratio, 0.317; 95% confidence interval, 0.129-0.776;
= 0.012).
A whole-blood RNA signature of PAH, which includes RNAs relevant to disease pathogenesis, associates with disease severity and identifies patients with poor clinical outcomes. Genetic variants associated with lower SMAD5 expression may increase susceptibility to PAH.
The perioperative bleeding risk associated with therapeutic anticoagulation at cardiac implantable electronic device implantation has previously been demonstrated to vary by the specific ...anticoagulant used. Although uninterrupted anticoagulation with warfarin appears to be safe, heparin products have been shown to increase the risk of perioperative bleeding. However, the risk associated with cardiac implantable electronic device implantation with anticoagulation using dabigatran, a novel oral direct thrombin inhibitor, is not known. We performed a prospective observational study of patients receiving dabigatran for anticoagulation who underwent cardiac implantable electronic device implantation from June 2011 through May 2012. The study end points included thromboembolic and bleeding complications within 30 days of surgery. Major bleeding complications were defined as bleeding requiring surgical intervention, prolongation of hospitalization, and discontinuation of the anticoagulant or transfusion of blood products within 30 days of surgery. Minor bleeding complications included the development of a hematoma not requiring additional intervention. The thrombotic end points included stroke, transient ischemic attack, myocardial infarction, pulmonary embolism, and deep vein thrombosis. A total of 25 patients were identified for inclusion. During the index hospitalization, no thromboembolic or bleeding complications developed. No major bleeding complications occurred within 30 days of surgery. One minor bleeding event (4%) occurred within 30 days of surgery in 1 patient who was also receiving dual antiplatelet therapy. In conclusion, although no thromboembolic or major bleeding events were observed, additional studies are required to define the optimal antithrombotic management in the perioperative period.
Objectives The purpose of this study was to examine the effects of alcohol septal ablation (ASA) on ventricular arrhythmias among patients with obstructive hypertrophic cardiomyopathy (HCM), as ...measured by appropriate implantable cardioverter-defibrillator (ICD) discharges. Background Alcohol septal ablation is an effective therapy for patients with symptomatic HCM. However, concern has been raised that ASA may be proarrhythmic secondary to the iatrogenic scar created during the procedure. The impact of ASA on ventricular arrhythmias has not been well described. Methods This prospective study included 123 consecutive patients with obstructive HCM who underwent ASA and had an ICD implanted for primary prevention of sudden cardiac death (SCD). The ICDs were implanted based on commonly accepted risk factors for SCD in the HCM population. Data from ICD interrogations during routine follow-up were collected. Results Nine appropriate ICD shocks were recorded over a mean follow-up of 2.9 years in the cohort, which had a mean of 1.5 ± 0.9 risk factors for SCD. Using Kaplan-Meier survival analysis, the estimated annual event rate was 2.8% over 3-year follow-up. There were no significant differences in the incidence of risk factors between patients who did and did not receive appropriate shocks. Conclusions The annual rate of appropriate ICD discharges after ASA is low and less than that reported previously for primary prevention of SCD in HCM. This suggests that ASA is not proarrhythmic. Traditional SCD risk factors did not predict ICD shocks in this cohort.
Summary Background The aim of this analysis was to examine associations between lung health in childhood and mortality between ages 18 and 44 years in the Tasmanian Longitudinal Health Study (TAHS). ...Methods The 1961 Tasmanian birth cohort who attended school in 1968 ( n = 8583) were linked to the Australian National Death Index (NDI) to identify deaths. Additional deaths were notified by families through a 37 year follow-up postal questionnaire. Information on lung health at age 7 years and on potential confounders was obtained from the original 1968 TAHS survey and school medical records. Cox proportional hazards modelling was used to assess determinants of mortality. Results A total of 264 (3%) deaths were identified. The principal causes of death were external injury (56.1%, n = 97) and cancer (17.9%, n = 31). Males were more likely than females to have died ( p = <0.1). Only two (1.1%) participants had died from respiratory conditions. Having an FEV1 < 80% predicted at 7 years of age was associated with a 2-fold increased incidence of death. Tonsillectomy before age 7 years was associated with a 1.5-fold increase in mortality ( p = 0.05); being male with a 3.6-fold increase in mortality ( p = 0.0001); and repeated chest illnesses at age 7 years causing >30 days confinement in the last year, was associated with a 2.2-fold increase in mortality ( p = 0.03). Conclusions Childhood lung health appears to be associated with increased mortality in adulthood, perhaps by affecting the ability to survive trauma, major illnesses and other physical stresses.
Context.
Realistic synthetic observations of theoretical source models are essential for our understanding of real observational data. In using synthetic data, one can verify the extent to which ...source parameters can be recovered and evaluate how various data corruption effects can be calibrated. These studies are the most important when proposing observations of new sources, in the characterization of the capabilities of new or upgraded instruments, and when verifying model-based theoretical predictions in a direct comparison with observational data.
Aims.
We present the SYnthetic Measurement creator for long Baseline Arrays (
SYMBA
), a novel synthetic data generation pipeline for Very Long Baseline Interferometry (VLBI) observations.
SYMBA
takes into account several realistic atmospheric, instrumental, and calibration effects.
Methods.
We used
SYMBA
to create synthetic observations for the Event Horizon Telescope (EHT), a millimetre VLBI array, which has recently captured the first image of a black hole shadow. After testing
SYMBA
with simple source and corruption models, we study the importance of including all corruption and calibration effects, compared to the addition of thermal noise only. Using synthetic data based on two example general relativistic magnetohydrodynamics (GRMHD) model images of M 87, we performed case studies to assess the image quality that can be obtained with the current and future EHT array for different weather conditions.
Results.
Our synthetic observations show that the effects of atmospheric and instrumental corruptions on the measured visibilities are significant. Despite these effects, we demonstrate how the overall structure of our GRMHD source models can be recovered robustly with the EHT2017 array after performing calibration steps, which include fringe fitting, a priori amplitude and network calibration, and self-calibration. With the planned addition of new stations to the EHT array in the coming years, images could be reconstructed with higher angular resolution and dynamic range. In our case study, these improvements allowed for a distinction between a thermal and a non-thermal GRMHD model based on salient features in reconstructed images.
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