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Study objective: Study the clinical outcomes associated with the number of concomitant vasopressors used in critically ill COVID-19 patients. Design: A single-center retrospective cohort study was conducted on patients admitted with COVID-19 to the intensive care unit (ICU) between March and October 2020. Setting: Rush University Medical Center, United States. Participants: Adult patients at least 18 years old with COVID-19 with continuous infusion of any vasopressors were included. Main outcome measures: 60-day mortality in COVID-19 patients by the number of concurrent vasopressors received. Results: A total of 637 patients met our inclusion criteria, of whom 338 (53.1 %) required the support of at least one vasopressor. When compared to patients with no vasopressor requirement, those who required 1 vasopressor (V1) (adjusted odds ratio [aOR] 3.27, 95 % confidence interval (CI) 1.86–5.79, p

Unsuppressed HIV viral load is an important marker of sustained HIV transmission. We investigated the prevalence, predictors, and high-risk areas of unsuppressed HIV viral load among HIV-positive men and women. Unsuppressed HIV viral load was defined as viral load of ≥400 copies/mL. Data from the HIV Incidence District Surveillance System (HIPSS), a longitudinal study undertaken between June 2014 to June 2016 among men and women aged 15–49 years in rural and peri-urban KwaZulu-Natal, South Africa, were analysed. A Bayesian geoadditive regression model which includes a spatial effect for a small enumeration area was applied using an integrated nested Laplace approximation (INLA) function while accounting for unobserved factors, non-linear effects of selected continuous variables, and spatial autocorrelation. The prevalence of unsuppressed HIV viral load was 46.1% [95% CI: 44.3–47.8]. Predictors of unsuppressed HIV viral load were incomplete high school education, being away from home for more than a month, alcohol consumption, no prior knowledge of HIV status, not ever tested for HIV, not on antiretroviral therapy (ART), on tuberculosis (TB) medication, having two or more sexual partners in the last 12 months, and having a CD4 cell count of

Background: There is a strong inverse relationship between final vessel diameter and subsequent risk of treatment failure after coronary stent deployment. The aim of this study was to investigate the magnitude by which stent delivery balloon underexpansion and stent elastic recoil contributed to suboptimal final vessel geometry. Methods: A prospective angiographic study recruiting 499 lesions (385 patients) undergoing coronary stent implantation was performed. Quantitative coronary angiography (QCA) was used to measure the minimal lumen diameters of the delivery balloon during stent deployment (MLD1) and of the stented segment following balloon deflation (MLD2). The expected balloon diameter for the deployment pressure was determined from the manufacturer's reference chart. Delivery balloon deficit was measured by subtracting the MLD1 from the expected balloon size and stent recoil was calculated by subtracting MLD2 from MLD1. Delivery balloon deficit and stent recoil were examined as a function of reference vessel diameter (RVD) and balloon-vessel (BV) ratio. Results: The final stent MLD was a mean 27.2% (SD = 7.2) less than the predicted diameter. The mean delivery balloon deficit was 0.65 mm (SD = 0.27) and the mean stent recoil was 0.28 mm (SD = 0.17). Percentage delivery balloon deficit and stent recoil were independent of RVD. Delivery balloon deficit increased with higher BV ratios. Stent recoil was independent of BV ratio and the use of predilatation. Conclusion: Failure to achieve predicted final stent diameter is a real problem with contribution from delivery balloon underexpansion and stent recoil. On average the final stent MLD is only 73% of the expected diameter, irrespective of vessel size. [ABSTRACT FROM AUTHOR]

Objective: QT peak prolongation is associated with left ventricular hypertrophy (LVH) in patients with hypertension. This study tests the hypothesis that QT peak prolongation correlates with LV mass index in apparently healthy young football players.Methods: QT peak and other ECG criteria for LVH were assessed in 117 male professional footballers (mean age 16.4 years +/- SD 0.76). Their left ventricular mass index (LVMI) was assessed by transthoracic echocardiography. Heart rate-corrected QT peak (QTpc) interval was measured in lead I using Bazett's formula. Spearman (2-tailed) test and UNIANOVA was used to assess if there were correlations between QT peak and the various echocardiographic and ECG indices of LVH.Results: Echocardiographic LVH, defined as LVMI > or = 134 g/m(2), was seen in 79 (70.5%) subjects. ECG-defined LVH was present in 54 (50 %) players by Sokolow-Lyon criteria, in 19 (16 %) players by Romhilt Score, in 5 (4 %) players by Cornell voltage criteria, and in 7 (6 %) players by Cornell product >2436 mm ms. There was no correlation between QT peak (QTpc) and LVMI on echocardiography (Spearman r = 0.058, 2-tailed P = 0.54). In addition, there was no relation between LVH and QTpc of lead I using any of the following ECG criteria: Sokolow-Lyon (P = 0.6), Romhilt (P = 0.3), Cornell voltage (P = 0.8), or Cornell product (P = 0.6).Conclusion: QT peak interval, which is associated with pathological LVH in hypertensive patients and is a measure of risk of cardiac death, does not correlate with LVH characterized by myocyte hypertrophy in young apparently healthy professional footballers. [ABSTRACT FROM AUTHOR]

Objective: To assess physiological cardiac adaptation in adolescent professional soccer players.Subjects and Design: Over a 32 month period 172 teenage soccer players were screened by echocardiography and ECG at a tertiary referral cardiothoracic centre. They were from six professional soccer teams in the north west of England, competing in the English Football League. One was excluded because of an atrial septal defect. The median age of the 171 players assessed was 16.7 years (5th to 95th centile range: 14-19) and median body surface area 1.68 m(2) (1.39-2.06 m(2)).Main Outcome Measures: Standard echocardiographic measurements were compared with predicted mean, lower, and upper limits in a cohort of normal controls after matching for age and surface area. Univariate regression analysis was used to assess the correlation between echocardiographic variables and the age and surface area of the soccer player cohort. ECG findings were also assessed.Results: All mean echocardiographic variables were greater than predicted for age and surface area matched controls (p < 0.001). All variables except left ventricular septal and posterior wall thickness showed a modest linear correlation with surface area (r = 0.2 to 0.4, p < 0.001); however, left ventricular mass was the only variable that was significantly correlated with age (r = 0.2, p < 0.01). Only six players (3.5%) had structural anomalies, none of which required further evaluation. All had normal left ventricular systolic function. Sinus bradycardia was found in 65 (39%). The Solokow-Lyon voltage criteria for left ventricular hypertrophy were present in 85 (50%) and the Romhilt-Estes points score (five or more) in 29 (17%). Repolarisation changes were present in 19 (11%), mainly in the inferior leads.Conclusions: Chamber dimensions, left ventricular wall thickness and mass, and aortic root size were all greater than predicted for controls after matching for age and surface area. Sinus bradycardia and the ECG criteria for left ventricular hypertrophy were common but there was poor correlation with echocardiographic left ventricular hypertrophy. The type of hypertrophy found reflected the combined endurance and strength based training undertaken. [ABSTRACT FROM AUTHOR]

The WIMS (Winfrith Improved Multigroup Scheme) reactor physics code is actively being developed for whole core modelling of a range of Small Modular Reactor types including the Pressurized Water Reactor (PWR), High Temperature Reactor (HTR), and Liquid Metal Cooled Fast reactor (LMFR). These developments include the capability for whole core multiphysics modelling with neutronics and thermal hydraulic feedback, as well as methods to determine the power deposition from neutron and gamma heating. Flux solutions are obtained using a wide variety of deterministic methods including diffusion theory, SP3, and full transport with the method of characteristics and Sn discrete ordinates methods, as well as multi-group Monte Carlo methods. The SP3 method allows both steady state and time dependent transient solutions by solving the time dependent SP3 equations. A wide variety of nuclear data libraries are available with WIMS including data from the JEF3.3, ENDF/B-VII.0 and CENDL3.1 nuclear data evaluations. This paper presents validation of the latest version of the WIMS code, WIMS11, for PWR and HTR systems. Comparisons are made against physics data obtained from the OECD/NEA PWR Watts Bar multi-physics benchmark and the IAEA HTR-10 benchmark, as well as neutron and gamma heating experiments that took place on the NESSUS reactor at Winfrith in the United Kingdom. In each case, validation of WIMS has been obtained by comparison either against measured data, or results provided by other benchmark participants that have been obtained with alternative deterministic or Monte Carlo methods.

For liquid metal-cooled fast reactors (LMFRs), improved predictive modelling is desirable to facilitate reactor licensing and operation and move towards a best estimate plus uncertainty (BEPU) approach. A key source of uncertainty in fast reactor calculations arises from the underlying nuclear data. Addressing the propagation of such uncertainties through multiphysics calculations schemes is therefore of importance, and is being addressed through international projects such as the Sodium-cooled Fast Reactor Uncertainty Analysis in Modelling (SFR-UAM) benchmark. In this paper, a methodology for propagation of nuclear data uncertainties within WIMS is presented. Uncertainties on key reactor physics parameters are calculated for selected SFR-UAM benchmark exercises, with good agreement with previous results. A methodology for coupled neutronic-thermal-hydraulic calculations within WIMS is developed, where thermal feedback is introduced to the neutronic solution through coupling with the ARTHUR subchannel code within WIMS and applied to steady-state analysis of the Horizon 2020 ESFR-SMART project reference core. Finally, integration of reactor physics and fuel performance calculations is demonstrated through linking of the WIMS reactor physics code to the TRAFIC fast reactor fuel performance code, through a Fortran-C-Python (FCP) interface. Given the 3D multiphysics calculation methodology, thermal-hydraulic and fuel performance uncertainties can ultimately be sampled alongside the nuclear data uncertainties. Together, these developments are therefore an important step towards enabling propagation of uncertainties through high fidelity, multiphysics SFR calculations and hence facilitate BEPU methodologies.

Until recently, criticality safety assessment codes had a minimum temperature at which calculations can be performed. Where criticality assessment has been required for lower temperatures, indirect methods, including reasoned argument or extrapolation, have been required to assess reactivity changes associated with these temperatures. The ANSWERS Software Service MONK® version 10B Monte Carlo criticality code, is capable of performing criticality calculations at any temperature, within the temperature limits of the underlying nuclear data in the BINGO continuous energy library. The temperature range of the nuclear data has been extended below the traditional lower limit of 293.6 K to 193 K in a prototype BINGO library, primarily based on JEFF-3.1.2 data. The temperature range of the thermal bound scattering data of the key moderator materials was extended by reprocessing the NJOY LEAPR inputs used to produce bound data for JEFF-3.1.2 and ENDF/B-VIII.0. To give confidence in the low temperature nuclear data, a series of MONK and MCBEND calculations have been performed and results compared against external data sources. MCBEND is a Monte Carlo code for shielding and dosimetry and shares commonalities to its sister code MONK including the BINGO nuclear data library. Good agreement has been achieved between calculated and experimental cross sections for ice, k-effective results for low temperature criticality benchmarks and calculated and experimentally determined eigenvalues for thermal neutron diffusion in ice. To quantify the differences between ice and water bound scattering data a number of MONK criticality calculations were performed for nuclear fuel transport flask configurations. The results obtained demonstrate good agreement with extrapolation methods. There is a discernible difference in the use of ice and water data.

The JEFF-3.3 and ENDF/B-VIII.0 evaluated nuclear data libraries were released in December 2017 and February 2018 respectively. Both evaluations represent a comprehensive update to their predecessor evaluations. The ANSWERS Software Service produces the MONK® and MCBEND Monte Carlo codes, and the WIMS deterministic code for nuclear criticality, shielding and reactor physics applications. MONK and MCBEND can utilise continuous energy nuclear data provided by the BINGO nuclear data library and MONK and WIMS can utilise broad energy group data (172 group XMAS scheme) via the WIMS nuclear data library. To produce the BINGO library, the BINGO Pre-Processor code is used to process ENDF-6 format evaluations. This utilises the RECONR-BROADR-PURR sequence of NJOY2016 to reconstruct and Doppler broaden the free gas neutron cross sections together with bespoke routines to generate cumulative distributions for the S(α,β) tabulations and equi-probable bins or probability functions for the secondary angle and energy data. To produce the WIMS library, NJOY2016 is again used to reconstruct and Doppler broaden the cross sections. The THERMR module is used to process the thermal scattering data. Preparation of data for system-dependent resonance shielding of some nuclides is performed. GROUPR is then used to produce the group averaged data before all the data are transformed into the specific WIMS library format. The MONK validation includes analyses based on around 800 configurations for a range of fuel and moderator types. The WIMS validation includes analyses of zero-energy critical and sub-critical, commissioning, operational and post-irradiation experiments for a range of fuel and moderator types. This paper presents and discusses the results of MONK and WIMS validation benchmark calculations using the JEFF-3.3 and ENDF/B-VIII.0 based BINGO and WIMS nuclear data libraries.

The ANSWERS Software Service is developing a number of techniques to better understand and quantify uncertainty on calculations of the neutron multiplication factor, k-effective, in nuclear fuel and other systems containing fissile material. The uncertainty on the calculated k-effective arises from a number of sources, including nuclear data uncertainties, manufacturing tolerances, modelling approximations and, for Monte Carlo simulation, stochastic uncertainty. For determining the uncertainties due to nuclear data, a set of application libraries have been generated for use with the MONK10 Monte Carlo and the WIMS10 deterministic criticality and reactor physics codes. This paper overviews the generation of these nuclear data libraries by Latin hypercube sampling of JEFF-3.1.2 evaluated data based upon a library of covariance data taken from JEFF, ENDF/B, JENDL and TENDL evaluations. Criticality calculations have been performed with MONK10 and WIMS10 using these sampled libraries for a number of benchmark models of fissile systems. Results are presented which show the uncertainty on k-effective for these systems arising from the uncertainty on the input nuclear data.

Background: Molecular testing of thyroid nodules is an essential tool to help risk stratify nodules with indeterminate cytology. Although ThyroSeq testing has been around for over a decade, there is a paucity of long-term follow-up data on cytologically indeterminate nodules that are determined to be molecularly negative or low-risk. The objective of this study is to assess the outcomes of nodules with indeterminate cytology (Bethesda III or IV) and negative or low-risk ThyroSeq results., Methods: This is a single academic institution retrospective cohort study. Patients with at least one thyroid nodule sampled with fine-needle aspiration who underwent ThyroSeq testing from 2012 to 2018 and had negative or low-risk ThyroSeq results on a cytologically indeterminate sample (n = 159 patients, 167 nodules) were included in the study. Outcomes include the false-negative rate and negative predictive value of each test version, as well as follow-up length for each nodule., Results: There were 159 patients with a mean age of 58 years (7-84 years) included in this study; the majority were female (81.8%). The mean follow-up was 4.0 years. Of 167 nodules, three were found to be malignant on resection (1.8%). The negative predictive value for the entire cohort was 98.2% and it was 89.3% for the surgical series., Conclusion: ThyroSeq testing has good negative predictive value and can help risk stratify cytologically indeterminate nodules. Routine follow-up allows for safe monitoring of nodules for features suggestive of malignancy., (© 2024 American Cancer Society.)

Cancer cachexia (CC) is a multifactorial wasting syndrome characterized by a significant loss in lean and/or fat mass and represents a leading cause of mortality in cancer patients. Nutraceutical treatments have been proposed as a potential treatment strategy to mitigate cachexia-induced muscle wasting. However, contradictory findings warrant further investigation. The purpose of this study was to determine the effects of leucine supplementation on skeletal muscle in male and female Apc Min/+ mice (APC). APC mice and their wild-type (WT) littermates were given normal drinking water or 1.5% leucine-supplemented water (n = 4-10/group/sex). We measured the gene expression of regulators of inflammation, protein balance, and myogenesis. Leucine treatment lowered survival rates, body mass, and muscle mass in males, while in females, it had no effect on body or muscle mass. Leucine treatment altered inflammatory gene expression by lowering Il1b 87% in the APC group and decreasing Tnfa 92% in both WT and APC males, while it had no effect in females ( p < 0.05). Leucine had no effect on regulators of protein balance and myogenesis in either sex. We demonstrated that leucine exacerbates moribundity in males and is not sufficient for mitigating muscle or fat loss during CC in either sex in the Apc Min/+ mouse., Competing Interests: The authors declare no conflict of interest.

Cachexia is characterized by losses in lean body mass and its progression results in worsened quality of life and exacerbated outcomes in cancer patients. However, the role and impact of fibrosis during the early stages and development of cachexia in under-investigated. The purpose of this study was to determine if fibrosis occurs during cachexia development, and to evaluate this in both sexes. Female and male C57BL6/J mice were injected with phosphate-buffered saline or Lewis Lung Carcinoma (LLC) at 8-week of age, and tumors were allowed to develop for 1, 2, 3, or 4 weeks. 3wk and 4wk female tumor-bearing mice displayed a dichotomy in tumor growth and were reassigned to high tumor (HT) and low tumor (LT) groups. In vitro analyses were also performed on cocultured C2C12 and 3T3 cells exposed to LLC conditioned media. Immunohistochemistry and quantitative polymerase chain reaction (qPCR) analysis were used to investigate fibrosis and fibrosis-related signaling in skeletal muscle. Collagen deposition in skeletal muscle was increased in the 1wk, LT, and HT groups in female mice. However, collagen deposition was only increased in the 4wk group in male mice. In general, female mice displayed earlier alterations in extracellular matrix (ECM)-related genes beginning at 1wk post-LLC injection. Whereas this was not seen in males. While overall tumor burden is tightly correlated to cachexia development in both sexes, fibrotic development is not. Male mice did not exhibit early-stage alterations in ECM-related genes contrary to what was noted in female mice., (© 2023 John Wiley & Sons Ltd.)