The role of different microstructural constituents on crack initiation in two-phase titanium alloys is still an area of great controversy. The present study investigates the effects of primary α ...volume fraction and concomitant macrozones on two different fatigue crack initiation modes concurrently observed in a near-α titanium alloy. Statistically representative regions were monitored in quasi-in-situ studies by interrupting fatigue testing to detect slip trace formation leading to crack initiation. In addition, high-resolution 2D strain maps were generated to quantify in-plane shear strains of slip traces related to microstructural features. The detailed analysis demonstrates that at 90% of the proof stress basal 〈a〉 slip plays a crucial role in crack initiation, regardless of whether cracking is transgranular or intergranular. In addition, a distinct shift from transgranular to intergranular crack initiation was observed with increasing αp fraction driven by the increased number of αp/αp grain boundaries. The high-resolution 2D strain mapping suggest that these intergranular cracks initiated from a burst of basal 〈a〉 slip starting from (0001) twist grain boundaries but penetrating one side of the grain pair in case of a partial (0001) twist grain boundary. From these observations, a new criterion for intergranular cracking is proposed based on a geometrical grain boundary parameter and the preference of neighbouring αp grain pair well aligned for basal 〈a〉 slip. It was found that while (0001) twist grain boundaries increase with increasing αp fraction, macrozones do not further enhance their frequency. However, macrozones of hard orientated grains did enhance transgranular crack formation by potentially higher local stress and increasing slip length over clustered αp grains with low misorientation reducing the requirement for out-of-plane shear.
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Objectives
To assess intraexaminer and interexaminer reliability of 3‐dimensional fetal sonographic measurements.
Methods
Three‐dimensional fetal organ volumes (head, kidney, total thigh volume, and ...fractional thigh volume) were acquired during the second and third trimesters, with the addition of placental volume in the second trimester, by 2 different experienced, blinded sonographers. Fifty‐eight fetuses were examined from 21 to 39 weeks' gestation. Intraexaminer and Interexaminer reliability was assessed with Bland‐Altman plots, and their 95% limits of agreement and intraclass correlation coefficients.
Results
The most significant interexaminer error was observed in the second‐trimester kidney volume (95% limits of agreement, ± 110%), and the best agreement was for the third‐trimester fractional thigh volume (95% limits of agreement, ± 25%) and second‐trimester head volume (95% limits of agreement, −7%–25%). Second‐ and third‐trimester intraclass correlation coefficient results were all greater than 0.75, apart from second‐trimester kidney volume intraexaminer (0.374) and interexaminer (0.061) measurements, second‐trimester placenta interexaminer measurements (0.390), and third‐trimester kidney interexaminer measurements (0.647).
Conclusions
Three‐dimensional fetal sonographic volumes of the head, kidney, total thigh, and placenta have limited reproducibility, and improvements in measurement techniques are needed before they can be used routinely to assess fetal growth. The 3‐dimensional fractional thigh volume can be reliably obtained in the late third trimester.
In the United States, reports about perioperative complications associated with bariatric surgery led to the establishment of accreditation criteria for bariatric centers of excellence and many ...bariatric centers obtaining accreditation. Currently, most bariatric procedures occur at these centers, but to what extent they uniformly provide high-quality care remains unknown.
To describe the variation in surgical outcomes across bariatric centers of excellence and the geographic availability of high-quality centers.
This retrospective review analyzed the claims data of 145 527 patients who underwent bariatric surgery at bariatric centers of excellence between January 1, 2010, and December 31, 2013. Data were obtained from the Healthcare Cost and Utilization Project's State Inpatient Database. This database included unique hospital identification numbers in 12 states (Arkansas, Arizona, Florida, Iowa, Massachusetts, Maryland, North Carolina, Nebraska, New Jersey, New York, Washington, and Wisconsin), allowing comparisons among 165 centers of excellence located in those states. Participants were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Those included in the study cohort were patients with a primary diagnosis of morbid obesity and who underwent laparoscopic Roux-en-Y gastric bypass, open Roux-en-Y gastric bypass, laparoscopic gastric band placement, or laparoscopic sleeve gastrectomy. Excluded from the cohort were patients younger than 18 years or who had an abdominal malignant neoplasm. Data were analyzed July 1, 2016, through January 10, 2017.
Risk-adjusted and reliability-adjusted serious complication rates within 30 days of the index operation were calculated for each center. Centers were stratified by geographic location and operative volume.
In this analysis of claims data from 145 527 patients, wide variation in quality was found across 165 bariatric centers of excellence, both nationwide and statewide. At the national level, the risk-adjusted and reliability-adjusted serious complication rates at each center varied 17-fold, ranging from 0.6% to 10.3%. At the state level, variation ranged from 2.1-fold (Wisconsin decile range, 1.5%-3.3%) to 9.5-fold (Nebraska decile range, 1.0%-10.3%). After dividing hospitals into quintiles of quality on the basis of their adjusted complication rates, 38 of 132 (28.8%) had a center in a higher quintile of quality located within the same hospital service area. Variation in rates of complications existed at centers with low volume (annual mean SD procedure volume, 156 20 patients; complication range, 0.6%-6.4%; 9.8-fold variation), medium volume (annual mean SD procedure volume, 239 27 patients; complication range, 0.6%-10.3%; 17.5-fold variation), and high volume (annual mean SD procedure volume, 448 131 patients; complication range, 0.6%-4.9%; 7.5-fold variation).
Even among accredited bariatric surgery centers, wide variation exists in rates of postoperative serious complications across geographic location and operative volumes. Given that a large proportion of centers are geographically located near higher-performing centers, opportunities for improvement through regional collaboratives or selective referral should be considered.
We present a 3D adaptive octree based numerical method for the simulation of binary solidification, with the temperature and the concentration fields being strongly coupled at the solidification ...front. The volume of fluid approach (VOF) is used to advance the front, which is geometrically reconstructed as a sharp interface separating the liquid and the solid domains. On basis of this, the embedded boundary method (EBM), together with the finite volume method, are employed to discretize the temperature and concentration fields at two sides of the interface in a sharp manner. The major novelty of the present study is displayed in several aspects: It is the first attempt to develop fully sharp schemes for the simulation of binary solidification in the VOF framework, while previous VOF-type methods consider the jump conditions at the interface as source terms; second the geometrically reconstructed interface and the EBM enable us to capture those discontinuities accurately without any artificial smearing, and particularly, we will show how to construct a second-order scheme for the flux jump condition of the temperature field across the interface; finally compared to other sharp schemes, we will show that the present method has natural advantages to adapt with the fluid flow solvers, because the hybrid VOF-EBM method guarantees good performance in solving the complex solid-fluid coupling problems based on the finite volume framework. Owing to all these advantages, we will show that regardless of pure substance or binary solution, all the numerical results agree well with the benchmark results. In particular, we apply the numerical method to model the solidification of a Ni-Cu alloy, which is thought to be very challenging owing to the high Lewis number. Besides, coupling to the fluid flow solver, we demonstrate that this method can predict the solidification/melting of an ice cylinder/sphere accurately in a salted solution under forced convection, by which the fluid, temperature and concentration equations are all solved sharply.
A hallmark of heart failure (HF), whether it presents itself during rest or periods of physical exertion, is the excessive elevation of intracardiac filling pressures at rest or with exercise. Many ...mechanisms contribute to the elevated intracardiac filling pressures, and notably, the concept of volume redistribution has gained attention as a cause of the elevated intracardiac filling pressures in patients with HF, particularly HF with preserved ejection fraction, who often present without symptoms at rest, with shortness of breath and fatigue appearing only during exertion. This phenomenon suggests cardiopulmonary system non-compliance and inappropriate volume distribution between the stressed and unstressed blood volume components. A substantial proportion of the intravascular blood volume is in the splanchnic vascular compartment in the abdomen. Preclinical and clinical investigations support the critical role of the sympathetic nervous system in modulating the capacitance and compliance of the splanchnic vascular bed via modulation of the greater splanchnic nerve (GSN). The GSN activation by stressors such as exercise causes excessive splanchnic vasoconstriction, which may contribute to the decompensation of chronic HF via volume redistribution from the splanchnic vascular bed to the central compartment. Accordingly, for example, GSN ablation for volume management has been proposed as a potential therapeutic intervention to increase unstressed blood volume. Here we provide a comprehensive review of the role of splanchnic circulation in the pathogenesis of HF and potential novel treatment options for redistributing blood volume to improve symptoms and prognosis in patients with HF.
Volume Redistribution Concept: Splanchnic Circulation. Display omitted
•The body's total blood volume is the sum of stressed and unstressed blood volume.•Splanchnic circulation constitutes the body's largest blood volume reservoir.•Volume redistribution may play a critical role in the congestion in heart failure.•Sympathetic nervous system controls splanchnic circulation via greater splanchnic nerve.•Splanchnic nerve modulation may serve a potential therapeutic use in heart failure.
Ion exchange is a pivotal method for enhancing the mechanical properties of oxide glasses, yet the influence of pressure on this process and its underlying mechanisms are not fully elucidated. This ...investigation pioneers the successful implementation of high-pressure ion exchange in commercial lithium aluminosilicate glass using Paterson press, achieving pressures above 100 MPa. Our findings unveil that moderate pressures promote ion interdiffusion, while extreme pressures hinder it due to glass network densification, which restricts ion mobility. Activation energy for ion exchange notably increases from 85.8 ± 0.7 kJ/mol at ambient pressure to 93.2 ± 4.6 kJ/mol at 50 MPa, highlighting the significant role of pressure on ion exchange kinetics. The large activation volume (∼146 cm3/mol) associated with the process underscores the extensive volume alterations involved in ion exchange. These insights underscore the potential of high-pressure processing in improving the mechanical properties of glass.
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•A cardio-pulmonary model developed from 3 chamber cardiovascular model and 1 chamber respiratory model.•Both models used to identify haemodynamic parameters of 4 pigs during a preload reduction ...manoeuvre.•Model outputs and parameters compared.•Analysis of effects of PEEP on haemodynamic parameters and model performance.
Background and objective: Mechanical ventilation causes adverse effects on the cardiovascular system. However, the exact nature of the effects on haemodynamic parameters is not fully understood. A recently developed cardio-vascular system model which incorporates cardio-pulmonary interactions is compared to the original 3-chamber cardiovascular model to investigate the exact effects of mechanical ventilation on haemodynamic parameters and to assess the trade-off of model complexity and model reliability between the 2 models.
Methods: Both the cardio-pulmonary and three chamber models are used to identify cardiovascular system parameters from aortic pressure, left ventricular volume, airway flow and airway pressure measurements from 4 pigs during a preload reduction manoeuvre. Outputs and parameter estimations from both models are contrasted to assess the relative performance of each model and to further investigate the effects of mechanical ventilation on haemodynamic parameters.
Results: Both models tracked measurements accurately as expected. There was no identifiable increase in error from the added complexity of the cardio-pulmonary model, with both models having a mean average error below 0.5% for all pigs. Identified left ventricle and vena cava elastances of the 3-chamber model was found to diverge exponentially with PEEP from identified left ventricle and vena cava elastances of the cardio-pulmonary model. The r2 of the fit for each pig ranged from 0.888 to 0.998 for left ventricle elastance divergence and from 0.905 to 0.999 for vena cava elastance divergence. All other identified parameters showed no significant difference between models.
Conclusions: Despite the increase in model complexity, there was no loss in the cardio-pulmonary model’s ability to accurately estimate haemodynamic parameters and reproduce system dynamics. Furthermore, the cardio-pulmonary model was able to demonstrate how mechanical ventilation affected parameter estimations as PEEP was increased. The 3-chamber model was shown to produce parameter estimations which diverged exponentially with PEEP, while the cardiopulmonary model estimations remained more stable, suggesting its ability to produce more physiologically accurate parameter estimations under higher PEEP conditions.
Whether disease burden in patients with metastatic castration-sensitive prostate cancer (mCSPC) predicts treatment outcomes is unknown. We assessed apalutamide treatment effect in TITAN patients with ...mCSPC by disease volume, metastasis number and timing of metastasis presentation.
These protocol-defined and post hoc analyses of the phase III randomised TITAN study evaluated clinical outcomes in patients receiving 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy (ADT). Subgroups were defined by volume (high: visceral and ≥1 bone metastases or ≥4 bone lesions with ≥1 beyond vertebral column/pelvis), development of metastases per conventional imaging (synchronous: at initial diagnosis; metachronous: after localised disease) and oligometastases (≤5 bone-only metastases) or polymetastases (>5 in bone ± other locations or ≤5 in bone plus other locations). Overall survival (OS), radiographic or second progression-free survival, and time to prostate-specific antigen progression or castration resistance were assessed using Cox proportional hazards models.
Of 1052 patients, 63%, 81%, 54%, 27%, 5.7%, and 8.0% had high-volume, synchronous, synchronous/high-volume, synchronous/low-volume, metachronous/high-volume, and metachronous/low-volume disease, respectively. The OS benefit favoured apalutamide plus ADT versus ADT alone in synchronous/high-volume (hazard ratio = 0.68 95% confidence interval: 0.53–0.87; p = 0.002), synchronous/low-volume (0.65 0.40–1.05; p = 0.08), metachronous/high-volume (0.69 0.33–1.44; p = 0.32) and metachronous/low-volume (0.22 0.09–0.55; p = 0.001) subgroups. Apalutamide improved other clinical outcomes regardless of subgroup, with similar safety profiles. Most favourable outcomes were observed in oligometastatic disease.
TITAN patients derived a robust benefit with apalutamide plus ADT regardless of disease volume and timing of metastasis presentation without differences in safety, supporting early apalutamide intensification in mCSPC.
NCT02489318.
•Apalutamide plus ADT improved outcomes in mCSPC regardless of disease burden.•Apalutamide improved outcomes in poor-prognosis subgroups.•Patients with oligometastatic bone-only disease benefitted most from apalutamide.•Apalutamide plus ADT was safe regardless of disease burden.
Pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF) is an increasingly recognized clinical complication of metabolic syndrome. No adequate animal model of ...PH-HFpEF is available, and no effective therapies have been identified to date. A recent study suggested that dietary nitrate improves insulin resistance in endothelial nitric oxide synthase null mice, and multiple studies have reported that both nitrate and its active metabolite, nitrite, have therapeutic activity in preclinical models of pulmonary hypertension.
To evaluate the efficacy and mechanism of nitrite in metabolic syndrome associated with PH-HFpEF, we developed a 2-hit PH-HFpEF model in rats with multiple features of metabolic syndrome attributable to double-leptin receptor defect (obese ZSF1) with the combined treatment of vascular endothelial growth factor receptor blocker SU5416. Chronic oral nitrite treatment improved hyperglycemia in obese ZSF1 rats by a process that requires skeletal muscle SIRT3-AMPK-GLUT4 signaling. The glucose-lowering effect of nitrite was abolished in SIRT3-deficient human skeletal muscle cells, and in SIRT3 knockout mice fed a high-fat diet, as well. Skeletal muscle biopsies from humans with metabolic syndrome after 12 weeks of oral sodium nitrite and nitrate treatment (IND#115926) displayed increased activation of SIRT3 and AMP-activated protein kinase. Finally, early treatments with nitrite and metformin at the time of SU5416 injection reduced pulmonary pressures and vascular remodeling in the PH-HFpEF model with robust activation of skeletal muscle SIRT3 and AMP-activated protein kinase.
These studies validate a rodent model of metabolic syndrome and PH-HFpEF, suggesting a potential role of nitrite and metformin as a preventative treatment for this disease.
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