A comprehensive evaluation of emergency department utilization by patients with cirrhosis.

BACKGROUND: Emergency Department (ED) based care is required for cirrhosis management, yet the burden of cirrhosis-related ED healthcare utilization (HCU) is understudied. We aimed to describe ED utilization within a statewide health system and compare the outcomes of high ED use (HEDU) versus non-HEDU in individuals with cirrhosis. METHODS: We retrospectively reviewed charts of adults with cirrhosis who presented to any of 16 EDs within the Indiana University Health system in 2021. Patient characteristics, features of the initial ED visit, subsequent 90-day healthcare use, and 360-day outcomes were collected. Multivariable logistic regression models were used to identify predictors HEDU status which was defined as ≥2 ED visits within 90 days after the index ED visit. RESULTS: There were 2124 eligible patients (mean age 61.3 years, 53% male, and 91% White). Major etiologies of cirrhosis were alcohol (38%), MASH (27%), and viral hepatitis (21%). Cirrhosis was newly diagnosed in the ED visit for 18.4%. Most common reasons for ED visits were abdominal pain (21%), shortness of breath (19%), and ascites/volume overload (16%). Of the initial ED visits 20% (n=424) were potentially avoidable. The overall 90-day mortality was 16%. Within 90 days, there were 366 HEDU (20%). Notable variables independently associated with HEDU were MELD-Na (aOR=1.044, 95% CI 1.005-1.085), prior ED encounter (aOR=1.520, 95% CI 1.136-2.034), and avoidable initial ED visit (aOR=1.938, 95% CI 1.014-3.703). CONCLUSIONS: Abdominal pain, shortness of breath, and ascites/fluid overload are the common presenting reasons for ED visits for patients with cirrhosis. Patients with cirrhosis presenting to the ED experience a 90-day mortality rate of 16%, and among those who initially visited the ED, 20% were HEDU. We identified several variables independently associated with HEDU. Our observations pave the way for developing interventions to optimize the care of patients with cirrhosis presenting to the ED and to lower repeated ED visits.

Diagnostic accuracy of prehospital lung ultrasound for acute decompensated heart failure: A systematic review and Meta-analysis.

BACKGROUND: Lung ultrasound (LUS) reduces time to diagnosis and treatment of acute decompensated heart failure (ADHF) in emergency department (ED) patients with undifferentiated dyspnea. We conducted a systematic review to evaluate the diagnostic accuracy and clinical impact of LUS for ADHF in the prehospital setting. METHODS: We performed a keyword search of multiple databases from inception through June 1, 2023. Included studies were those enrolling prehospital patients with undifferentiated dyspnea or suspected ADHF, and specifically diagnostic studies comparing prehospital LUS to a gold standard and intervention studies with a non-US comparator group. Title and abstract screening, full text review, risk of bias (ROB) assessments, and data extraction were performed by multiple authors. and adjudicated. The primary outcome was pooled sensitivity, specificity, and diagnostic likelihood ratios (LR) for prehospital LUS. A test-treatment threshold of 0.7 was applied based on prior ADHF literature in the ED. Intervention outcomes included mortality, mechanical ventilation, and time to HF specific treatment. RESULTS: Eight diagnostic studies (n = 691) and two intervention studies (n = 70) met inclusion criteria. No diagnostic studies were low-ROB. Both intervention studies were critical-ROB, and not pooled. Pooled sensitivity and specificity of prehospital LUS for ADHF were 86.7% (95%CI:70.8%-94.6%) and 87.5% (78.2%-93.2%), respectively, with similar performance by physician vs. paramedic LUS and number of lung zones evaluated. Pooled LR+ and LR- were 7.27 (95% CI: 3.69-13.10) and 0.17 (95% CI: 0.06-0.34), respectively. Area under the summary receiver operating characteristic curve was 0.922. At the observed 42.4% ADHF prevalence (pre-test probability), positive pre-hospital LUS exceeded the 70% threshold to initiate treatment (post-test probability 84%, 80-88%). CONCLUSIONS: LUS had similar diagnostic test characteristics for ADHF diagnosis in the prehospital setting as in the ED. A positive prehospital LUS may be sufficient to initiate early ADHF treatment based on published test-treatment thresholds. More studies are needed to determine the clinical impact of prehospital LUS.

Role of electron localisation in H adsorption and hydride formation in the Mg basal plane under aqueous corrosion: a first-principles study.

Understanding hydrogen-metal interactions is important in various fields of surface science, including the aqueous corrosion of metals. The interaction between atomic H and a Mg surface is a key process for the formation of sub-surface Mg hydride, which may play an important role in Mg aqueous corrosion. In the present work, we performed first-principles Density Functional Theory (DFT) calculations to study the mechanisms for hydrogen adsorption and crystalline Mg hydride formation under aqueous conditions. The Electron Localisation Function (ELF) is found to be a promising indicator for predicting stable H adsorption in the Mg surface. It is found that H adsorption and hydride layer formation is dominated by high ELF adsorption sites. Our calculations suggest that the on-surface adsorption of atomic H, OH radicals and atomic O could enhance the electron localisation at specific sites in the sub-surface region, thus forming effective H traps locally. This is predicted to result in the formation of a thermodynamically stable sub-surface hydride layer, which is a potential precursor of the crucial hydride corrosion product of magnesium.

Corrosion inhibition in acidic environments: key interfacial insights with photoelectron spectroscopy.

In many engineering scenarios, surface-active organic species are added to acidic solutions to inhibit the corrosion of metallic components. Given suitable selection, such corrosion inhibitors are highly effective, preventing significant degradation even in highly aggressive environments. Nevertheless, there are still considerable gaps in fundamental knowledge of corrosion inhibitor functionality, severely restricting rational development. Here, we demonstrate the capability of X-ray photoelectron spectroscopy (XPS), supported by ab initio modelling, for revealing key details of inhibited substrates. Attention is focussed on the corrosion inhibition of carbon steel through the addition of an exemplar imidazoline-based corrosion inhibitor (OMID) to aqueous solutions of both HCl and H2SO4. Most notably, it is demonstrated that interfacial chemistry varies with the identity of the acid. High resolution Fe 2p, O 1s, N 1s, and Cl 2p XPS spectra, acquired from well-inhibited carbon steel in 1 M HCl, show that there are two different singly protonated OMID species bound directly to the metallic carbon steel substrate. In sharp contrast, in 0.01 M H2SO4, OMID adsorbs onto an ultra-thin surface film, composed primarily of a ferric sulfate (Fe2(SO4)3)-like phase. Such insight is essential to efforts to develop a mechanistic description of corrosion inhibitor functionality, as well as knowledge-based identification of next generation corrosion inhibitors.

A transferable prediction model of molecular adsorption on metals based on adsorbate and substrate properties.

Surface adsorption is one of the fundamental processes in numerous fields, including catalysis, the environment, energy and medicine. The development of an adsorption model which provides an effective prediction of binding energy in minutes has been a long term goal in surface and interface science. The solution has been elusive as identifying the intrinsic determinants of the adsorption energy for various compositions, structures and environments is non-trivial. We introduce a new and flexible model for predicting adsorption energies to metal substrates. The model is based on easily computed, intrinsic properties of the substrate and adsorbate, which are the same for all the considered systems. It is parameterised using machine learning based on first-principles calculations of probe molecules (e.g., H2O, CO2, O2, N2) adsorbed to a range of pure metal substrates. The model predicts the computed dissociative adsorption energy to metal surfaces with a correlation coefficient of 0.93 and a mean absolute error of 0.77 eV for the large database of molecular adsorption energies provided by Catalysis-Hub.org which have a range of 15 eV. As the model is based on pre-computed quantities it provides near-instantaneous estimates of adsorption energies and it is sufficiently accurate to eliminate around 90% of candidates in screening study of new adsorbates. The model, therefore, significantly enhances current efforts to identify new molecular coatings in many applied research fields.

Ultrafiltration for acute heart failure.

BACKGROUND: Pharmacotherapies such as loop diuretics are the cornerstone treatment for acute heart failure (AHF), but resistance and poor response can occur. Ultrafiltration (UF) is an alternative therapy to reduce congestion, however its benefits, efficacy and safety are unclear. OBJECTIVES: To assess the effects of UF compared to diuretic therapy on clinical outcomes such as mortality and rehospitalisation rates. SEARCH METHODS: We undertook a systematic search in June 2021 of the following databases: CENTRAL, MEDLINE, Embase, Web of Science CPCI-S and ClinicalTrials.gov. We also searched the WHO ICTRP platform in October 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared UF to diuretics in adults with AHF. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We contacted study authors for any further information, and language interpreters to translate texts. We assessed risk of bias in included studies using Risk of Bias 2 (RoB2) tool and assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included 14 trials involving 1190 people. We included people who had clinical signs of acute hypervolaemia. We excluded critically unwell people such as those with ischaemia or haemodynamic instability. Mean age ranged from 57.5 to 75 years, and the setting was a mix of single and multi-centre. Two trials researched UF as a complimentary therapy to diuretics, while the remaining trials withheld diuretic use during UF. There was high risk of bias in some studies, particularly with deviations from the intended protocols from high cross-overs as well as missing outcome data for long-term follow-up.  We are uncertain about the effect of UF on all-cause mortality at 30 days or less (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.13 to 2.85; 3 studies, 286 participants; very low-certainty evidence). UF may have little to no effect on all-cause mortality at the longest available follow-up (RR 1.00, 95% CI 0.73 to 1.36; 9 studies, 987 participants; low-certainty evidence). UF may reduce all-cause rehospitalisation at 30 days or less (RR 0.76, 95% CI 0.53 to 1.09; 3 studies, 337 participants; low-certainty evidence). UF may slightly reduce all-cause rehospitalisation at longest available follow-up (RR 0.91, 95% CI 0.79 to 1.05; 6 studies, 612 participants; low-certainty evidence). UF may reduce heart failure-related rehospitalisation at 30 days or less (RR 0.62, 95% CI 0.37 to 1.04; 2 studies, 395 participants; low-certainty evidence). UF probably reduces heart failure-related rehospitalisation at longest available follow-up, with a number needed to treat for an additional beneficial effect (NNTB) of 10 (RR 0.69, 95% CI 0.53 to 0.90; 4 studies, 636 participants; moderate-certainty evidence).  No studies measured need for mechanical ventilation.  UF may have little or no effect on serum creatinine change at 30 days since discharge (mean difference (MD) 14%, 95% CI -12% to 40%; 1 study, 221 participants; low-certainty evidence). UF may increase the risk of new initiation of renal replacement therapy at longest available follow-up (RR 1.42, 95% CI 0.42 to 4.75; 4 studies, 332 participants; low-certainty evidence).  There is an uncertain effect of UF on the risk of complications from central line insertion in hospital (RR 4.16, 95% CI 1.30 to 13.30; 6 studies, 779 participants; very low-certainty evidence).  AUTHORS' CONCLUSIONS: This review summarises the latest evidence on UF in AHF. Moderate-certainty evidence shows UF probably reduces heart failure-related rehospitalisation in the long term, with an NNTB of 10. UF may reduce all-cause rehospitalisation at 30 days or less and at longest available follow-up. The effect of UF on all-cause mortality at 30 days or less is unclear, and it may have little effect on all-cause mortality in the long-term.  While UF may have little or no effect on serum creatinine change at 30 days, it may increase the risk of new initiation of renal replacement therapy in the long term. The effect on complications from central line insertion is unclear.  There is insufficient evidence to determine the true impact of UF on AHF. Future research should evaluate UF as an adjunct therapy, focusing on outcomes such as heart failure-related rehospitalisation, cardiac mortality and renal outcomes at medium- to long-term follow-up.

Right ventricular dysfunction in acute heart failure from emergency department to discharge: Predictors and clinical implications.

BACKGROUND: Among acute heart failure (AHF) inpatients, right ventricular dysfunction (RVD) predicts clinical outcomes independent of left ventricular (LV) dysfunction. Prior studies have not accounted for congestion severity, show conflicting findings on echocardiography (echo) timing, and excluded emergency department (ED) patients. We describe for the first time the epidemiology, predictors, and outcomes of RVD in AHF starting with earliest ED treatment. METHODS: Point-of-care echo and 10-point lung ultrasound (LUS) were obtained in 84 prospectively enrolled AHF patients at two EDs, ≤1 h after first intravenous diuresis, vasodilator, and/or positive pressure ventilation (PPV). Echo and LUS were repeated at 24, 72, and 168 h, unless discharged sooner (n = 197 exams). RVD was defined as <17 mm tricuspid annulus plane systolic excursion (TAPSE), our primary measure. To identify correlates of RVD, a multivariable linear mixed model (LMM) of TAPSE through time was fit. Possible predictors were specified a priori and/or with p ≤ 0.1 difference between patients with/without RVD. Data were standardized and centered to facilitate comparison of relative strength of association between predictors of TAPSE. Survival curves for a 30-day death or AHF readmission primary outcome were assessed for RVD, LUS severity, and LVEF. A multivariable generalized linear mixed model (GLMM) for the outcome was used to adjust RVD for LVEF and LUS. RESULTS: 46% (n = 39) of patients at ED arrival showed RVD by TAPSE (median 18 mm, interquartile range 13-23). 18 variables with p ≤ 0.1 unadjusted difference with/without RVD, and 12 a priori predictors of RVD were included in the multivariable LMM model of TAPSE through time (R2 = 0.76). Missed antihypertensive medication (within 7 days), ED PPV, chronic obstructive pulmonary disease history, LVEF, LUS congestion severity, and right ventricular systolic pressure (RVSP) were the strongest multivariable predictors of RVD, respectively, and the only to reach statistical significance (p < 0.05). 30-day death or AHF readmission was associated with RVD at ED arrival (hazard ratio {HR} 3.31 {95%CI: 1.28-8.53}, p = 0.009), ED to discharge decrease in LUS (HR 0.11 {0.01-0.85}, p < 0.0001 for top quartile Δ), but not LVEF (quartile 2 vs. 1 HR 0.78 {0.22-2.68}, 3 vs. 1 HR 0.55 {0.16-1.92}, 4 vs. 1 HR 0.32 {0.09-1.22}, p = 0.30). The area under the receiver operating curve on GLMM for the primary outcome by TAPSE (p = 0.0012), ΔLUS (p = 0.0005), and LVEF (p = 0.8347) was 0.807. CONCLUSION: In this observational study, RVD was common in AHF, and predicted by congestion on LUS, LVEF, RVSP, and comorbidities from ED arrival through discharge. 30-day death or AHF-rehospitalization was associated with RVD at ED arrival and ΔLUS severity, but not LVEF.

Do septic patients with reduced left ventricular ejection fraction require a low-volume resuscitative strategy?

BACKGROUND: Many clinicians are wary of administering 30 cc/kg of intravenous fluid (IVF) to septic patients with reduced left-ventricular ejection fraction (rLVEF), fearing volume overload. Prior studies have used history of heart failure, rather than LVEF measured at presentation, thereby potentially distorting the relationship between rLVEF, IVF, and adverse outcomes. Our goal was to assess the relationship between IVF volume and outcomes in patients with, versus without, rLVEF. METHODS: This was a prospective observational study performed at an urban Emergency Department (ED). Included patients were adults with suspected sepsis, defined as being treated for infection plus either systolic blood pressure <90 mm/Hg or lactate >2 mmol/L. All patients had LVEF assessed by ED echocardiogram, prior to receipt of >1 l IVF. MEASUREMENTS AND MAIN RESULTS: We enrolled 73 patients, of whom 33 had rLVEF, defined as <40%. Patients with rLVEF were older, had greater initial lactate, more ICU admission, and more vasopressor use. IVF volume was similar between LVEF groups at 3-h (2.2 (IQR 0.8) vs 2.0 (IQR 2.4) liters) while patients with rLVEF were more likely to achieve 30 cc/kg (61% (CI 44-75) vs 45% (CI 31-60). In the reduced versus not-reduced LVEF groups, hospital days, ICU days, and ventilator days were similar: 8 (IQR 7) vs 6.5 (8.5) days, 7 (IQR 7) vs 5 (4) days, and 4 (IQR 8) vs. 5 (10) days, respectively. CONCLUSIONS: Septic patients with rLVEF at presentation received similar volume of IVF as those without rLVEF, without an increase in adverse outcomes attributable to volume overload. While validation is needed, our results suggest that limiting IVF administration in the setting of rLVEF is not necessary.

Diagnostic delay in axial spondyloarthritis: a systematic review and meta-analysis.

BACKGROUND: Delay to diagnosis in axial SpA (axSpA) is longer than in many other rheumatic diseases. Prolonged delay is associate with poorer outcomes, including functional impairment and quality of life. Our aims were to describe global variation in delay to diagnosis, factors associated with delay, and delay compared with PsA. METHODS: We searched MEDLINE, PubMed, Embase and Web of Science using a predefined protocol. Diagnostic delay was defined as years between the age at symptom onset and at diagnosis. We pooled the mean delay using random effects inverse variance meta-analysis. We examined variations in pooled estimates using prespecified subgroup analyses and sources of heterogeneity using meta-regression. RESULTS: A total of 64 studies reported the mean diagnostic delay in axSpA patients. The pooled mean delay was 6.7 years (95% CI 6.2, 7.2) with high levels of heterogeneity. Delay to diagnosis did not improve over time when stratifying results by year of publication. Studies from high-income countries (defined by the World Bank) reported longer delays than those from middle-income countries. Factors consistently reported to be associated with longer delays were lower education levels, younger age at symptom onset and absence of extra-articular manifestations (EAMs). The pooled estimate for diagnostic delay from 8 PsA studies was significantly shorter, at 2.6 years (95% CI 1.6, 3.6). CONCLUSION: For axSpA patients, delay to diagnosis remains unacceptably prolonged in many parts of the world. Patient factors (e.g. education) and disease presentation (onset age and EAMs) should inform campaigns to improve delay.

Blood Pressure Reduction in Hypertensive Acute Heart Failure.

PURPOSE OF REVIEW: To review the key clinical and research questions regarding blood pressure (BP) reduction with vasodilators in the early management of hypertensive acute heart failure (H-AHF). RECENT FINDINGS: Despite numerous AHF vasodilator clinical trials in the past two decades, virtually none has studied a population where vasoconstriction is the predominant physiology, and with the agents and doses most commonly used in contemporary practice. AHF patients are remarkably heterogenous by vascular tone, and this heterogeneity is not always discernible through BP or clinical exam. Emerging data suggest that diastolic BP may be a stronger correlate of vascular tone in AHF than systolic BP, despite the latter historically serving as a key inclusion criterion for vasodilator clinical trials. Existing data are limited. A clinical trial that evaluates vasodilators in a manner of use consistent with contemporary practice, specifically within the subpopulation of patients with true H-AHF, is greatly needed. Until then, observational data supports long-standing vasodilators such as nitroglycerin, administered by IV bolus, and with goal reduction of SBP ≤25% as a safe first-line approach for patients with severe H-AHF presentations.

Effects of the COVID-19 pandemic on out-of-hospital cardiac arrest care in Detroit.

INTRODUCTION: In response to the COVID-19 pandemic in Detroit, an earlier termination of resuscitation protocol was initiated in March 2020. To characterize pre-hospital cardiac arrest careduring COVID-19 in Detroit, we analyzed out-of-hospital cardiac arrest (OHCA) rate of ROSC (return of spontaneous circulation) and patient characteristics before and during the COVID-19 pandemic. METHODS: OHCA data was analyzed between March 10th, 2020 - April 30th, 2020 and March 10th, 2019 - April 30th, 2019. ROSC, patient demographics, arrest location, initial rhythms, bystander CPR and field termination were compared before and during the pandemic. Descriptive statistics were utilized to compare arrest characteristics between years, and the odds of achieving vs. not achieving ROSC. 2020 vs. 2019 as a predictor for ROSC was assessed with logistic regression. RESULTS: 471 patients were included. Arrests increased to 291 during the pandemic vs. 180 in 2019 (62% increase). Age (mean difference + 6; 95% CI: +2.4 to +9.5), arrest location (nursing home OR = 2.42; 95% CI: 1.42-4.31; public place OR = 0.47; 95% CI: 0.25-0.88), BLS response (OR = 0.68; 95% CI: 0.47-0.99), and field termination of resuscitation (OR = 2.36; 95% CI: 1.36-4.07) differed significantly in 2020 compared to 2019. No significant difference was found in the confounder-adjusted odds of ROSC in 2020 vs 2019 (OR = 0.61; 95% CI: 0.34-1.11). CONCLUSION: OHCA increased by 62% during COVID-19 in Detroit, without a significant change in prehospital ROSC. The rate of ROSC remained similar despite the implementation of an early termination of resuscitation protocol in response to COVID-19.

Prevalence of extra-articular manifestations in psoriatic arthritis: a systematic review and meta-analysis.

OBJECTIVE: To describe the prevalence of extra-articular manifestations-enthesitis, dactylitis, nail disease, uveitis and IBD-in PsA, and their impact on longitudinal disease outcomes. METHODS: We searched Medline, PubMed, Scopus and Web of Science using a predefined protocol in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies using imaging to define extra-articular manifestations (EAMs) were excluded. Where possible, we performed meta-analyses of prevalence estimates, reported as percentages (95% CI). Heterogeneity (I2 statistic) was examined according to study characteristics. RESULTS: We identified 65 studies amounting to a total of 163 299 PsA patients. Enthesitis was assessed in 29 studies with an average prevalence of 30% (95% CI: 24%, 38%). Dactylitis was reported in 35 studies with an average prevalence of 25% (95% CI: 20%, 31%). Nail disease was present in 60% (95% CI: 52%, 68%) across 26 studies, but definitions were often unclear. Uveitis (3.2%; 95% CI: 1.9%, 5.3%) and IBD (3.3%; 95% CI: 1.5%, 7.1%) were less common. Heterogeneity was high (>95%) in all meta-analyses, but could not be explained by study characteristics. No studies examined the impact of EAMs on longitudinal disease outcomes, except that dactylitis increases radiographic progression. CONCLUSION: Enthesitis, dactylitis and nail disease are highly prevalent in PsA, but not uveitis and IBD. EAM patterns differ from axial SpA despite their shared disease mechanisms, which may help further understand differences between spondyloarthritides. More studies are needed on the impact of EAMs on disease outcomes such as response to treatment.

The CRYSTAL code, 1976-2020 and beyond, a long story.

CRYSTAL is a periodic ab initio code that uses a Gaussian-type basis set to express crystalline orbitals (i.e., Bloch functions). The use of atom-centered basis functions allows treating 3D (crystals), 2D (slabs), 1D (polymers), and 0D (molecules) systems on the same grounds. In turn, all-electron calculations are inherently permitted along with pseudopotential strategies. A variety of density functionals are implemented, including global and range-separated hybrids of various natures and, as an extreme case, Hartree-Fock (HF). The cost for HF or hybrids is only about 3-5 times higher than when using the local density approximation or the generalized gradient approximation. Symmetry is fully exploited at all steps of the calculation. Many tools are available to modify the structure as given in input and simplify the construction of complicated objects, such as slabs, nanotubes, molecules, and clusters. Many tensorial properties can be evaluated by using a single input keyword: elastic, piezoelectric, photoelastic, dielectric, first and second hyperpolarizabilities, etc. The calculation of infrared and Raman spectra is available, and the intensities are computed analytically. Automated tools are available for the generation of the relevant configurations of solid solutions and/or disordered systems. Three versions of the code exist: serial, parallel, and massive-parallel. In the second one, the most relevant matrices are duplicated on each core, whereas in the third one, the Fock matrix is distributed for diagonalization. All the relevant vectors are dynamically allocated and deallocated after use, making the code very agile. CRYSTAL can be used efficiently on high performance computing machines up to thousands of cores.

The Role of Troponin for Acute Heart Failure.

PURPOSE OF REVIEW: To review the mechanisms, clinical interpretation, prognostic role, and future research regarding cardiac troponin (cTn) in the assessment of acute heart failure (AHF) patients presenting to the emergency department (ED). RECENT FINDINGS: cTn has become a necessary component of the evaluation of AHF patients in the ED, largely because of its independently predictive value as a prognosticator of poor outcome. High-sensitivity assays (hs-cTn) may add risk stratification value beyond conventional assays, specifically with regard to identifying low-risk AHF patients. Moreover, as the complex mechanisms of cTn release in AHF continue to be elucidated, recent studies suggest that many of the key hemodynamic derangements that define specific AHF syndromes may also be direct culprits in cTn release. cTn is released in AHF in response to both non-ischemic (e.g., increased afterload, increased preload, inflammatory signaling, altered calcium handling) and ischemic mechanisms. cTn detectable on conventional sensitivity assays predicts poor prognosis when measured in the ED or when noted in historical data such as past ED visits or at the time of discharge from the most recent AHF hospitalization. hs-cTn assays provide detectable values in nearly all AHF patients. Evidence is evolving on using hs-cTn levels below the upper limit of normal to potentially identify low-risk ED patients, and further research is needed. Among the classically cited risk factors for AHF mortality, cTn and natriuretic peptides stand as independent and synergistic prognostic factors even after adjustment for confounders. Many other risk factors, such as ejection fraction, often failed to retain ED prognostic value beyond these two biomarkers.

Pulmonary oxygen uptake and muscle deoxygenation kinetics during heavy intensity cycling exercise in patients with emphysema and idiopathic pulmonary fibrosis.

BACKGROUND: Little is known about the mechanistic basis for the exercise intolerance characteristic of patients with respiratory disease; a lack of clearly defined, distinct patient groups limits interpretation of many studies. The purpose of this pilot study was to investigate the pulmonary oxygen uptake ([Formula: see text] O2) response, and its potential determinants, in patients with emphysema and idiopathic pulmonary fibrosis (IPF). METHODS: Following a ramp incremental test for the determination of peak [Formula: see text] O2 and the gas exchange threshold, six emphysema (66 ± 7 years; FEV1, 36 ± 16%), five IPF (65 ± 12 years; FEV1, 82 ± 11%) and ten healthy control participants (63 ± 6 years) completed three repeat, heavy-intensity exercise transitions on a cycle ergometer. Throughout each transition, pulmonary gas exchange, heart rate and muscle deoxygenation ([HHb], patients only) were assessed continuously and subsequently modelled using a mono-exponential with ([Formula: see text] O2, [HHb]) or without (HR) a time delay. RESULTS: The [Formula: see text] O2 phase II time-constant (τ) did not differ between IPF and emphysema, with both groups significantly slower than healthy controls (Emphysema, 65 ± 11; IPF, 69 ± 7; Control, 31 ± 7 s; P < 0.05). The HR τ was slower in emphysema relative to IPF, with both groups significantly slower than controls (Emphysema, 87 ± 19; IPF, 119 ± 20; Control, 58 ± 11 s; P < 0.05). In contrast, neither the [HHb] τ nor [HHb]:O2 ratio differed between patient groups. CONCLUSIONS: The slower [Formula: see text] O2 kinetics in emphysema and IPF may reflect poorer matching of O2 delivery-to-utilisation. Our findings extend our understanding of the exercise dysfunction in patients with respiratory disease and may help to inform the development of appropriately targeted rehabilitation strategies.

The atomistic structure of yttria stabilised zirconia at 6.7 mol%: an ab initio study.

Yttria stabilized zirconia (YSZ) is an important oxide ion conductor used in solid oxide fuel cells, oxygen sensing devices, and for oxygen separation. Doping pure zirconia (ZrO2) with yttria (Y2O3) stabilizes the cubic structure against phonon induced distortions and this facilitates high oxide ion conductivity. The local atomic structure of the dopant is, however, not fully understood. X-ray and neutron diffraction experiments have established that, for dopant concentrations below 40 mol% Y2O3, no long range order is established. A variety of local structures have been suggested on the basis of theoretical and computational models of dopant energetics. These studies have been restricted by the difficulty of establishing force field models with predictive accuracy or exploring the large space of dopant configurations with first principles theory. In the current study a comprehensive search for all symmetry independent configurations (2857 candidates) is performed for 6.7 mol% YSZ modelled in a 2 × 2 × 2 periodic supercell using gradient corrected density functional theory. The lowest energy dopant structures are found to have oxygen vacancy pairs preferentially aligned along the 〈210〉 crystallographic direction in contrast to previous results which have suggested that orientation along the 〈111〉 orientation is favourable. Analysis of the defect structures suggests that the Y3+-Ovac interatomic separation is an important parameter for determining the relative configurational energies. Current force field models are found to be poor predictors of the lowest energy structures. It is suggested that the energies from a simple point charge model evaluated at unrelaxed geometries is actually a better descriptor of the energy ordering of dopant structures. Using these observations a pragmatic procedure for identifying low energy structures in more complicated material models is suggested. Calculation of the oxygen vacancy migration activation energies within the lowest energy 〈210〉 oriented structures gives results consistent with experimental observations.

A hybrid-exchange density functional study of the bonding and electronic structure in bulk CuFeS2.

The geometric, electronic, and magnetic properties of bulk chalcopyrite CuFeS2 have been investigated using hybrid-exchange density functional theory calculations. The results are compared with available theoretical and experimental data. The theoretical description of the bonding and electronic structure in CuFeS2 is analyzed in detail and compared to those computed for chalcocite (CuS2) and greigite (Fe3S4). In particular, the behavior of the 3d electrons of Fe(3+) is discussed in terms of the Hubbard-Anderson model in the strongly correlated regime and found to be similarly described in both materials by an on-site Coulomb repulsion (U) of ∼8.9 eV and a transfer integral (t) of ∼0.3 eV.

Zebrafish Models of Human Leukemia: Technological Advances and Mechanistic Insights.

Insights concerning leukemic pathophysiology have been acquired in various animal models and further efforts to understand the mechanisms underlying leukemic treatment resistance and disease relapse promise to improve therapeutic strategies. The zebrafish (Danio rerio) is a vertebrate organism with a conserved hematopoietic program and unique experimental strengths suiting it for the investigation of human leukemia. Recent technological advances in zebrafish research including efficient transgenesis, precise genome editing, and straightforward transplantation techniques have led to the generation of a number of leukemia models. The transparency of the zebrafish when coupled with improved lineage-tracing and imaging techniques has revealed exquisite details of leukemic initiation, progression, and regression. With these advantages, the zebrafish represents a unique experimental system for leukemic research and additionally, advances in zebrafish-based high-throughput drug screening promise to hasten the discovery of novel leukemia therapeutics. To date, investigators have accumulated knowledge of the genetic underpinnings critical to leukemic transformation and treatment resistance and without doubt, zebrafish are rapidly expanding our understanding of disease mechanisms and helping to shape therapeutic strategies for improved outcomes in leukemic patients.