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The non-linear Generalized Hoek-Brown (GHB) failure criterion for rock mass is widely accepted and has been applied in a large number of open pits slope designs. This paper proposes new equations for estimating the maximum confining stress from the (GHB) parameters and geometrical properties of the slope in the case where the strength ratio is critical (SR)_crit=(σ_ci/γH)_crit and the factor of safety (FOS)=1. This maximum confining stress can be used to calculate the global equivalent Mohr-Coulomb (MC) parameters. It was found that, compared to the calculation with the limit analysis method (LAM), the discrepancies do not exceed 5% and remain in the most cases less than 1%. Hence, the estimation of the (FOS) is much more improved, because the comparison of the literature’s results with the (LAM) leaded to a difference up to 21%. For any value of (FOS≠1), an iterative method has been proposed to evaluate (SR)_crit. The comparison between the results driven from this method and those of (LAM) showed a good agreement, which proves its accuracy. A case study has been conducted in an open pit located in Sudan to evaluate the discrepancy of the (FOS) provided by different methods using limit equilibrium method (LEM) with Rocscience Slide software and using the (LAM) given in the form of charts.

The effects of uncertainties on the nonlinear dynamics of complex structures remain poorly mastered and most methods deal with the linear case. This article deals with a model of a large and complex structure with uncertain parameters for the nonlinear dynamic case, and the reduction in the model discretized by the finite element method is obtained by reducing the degrees of freedom in the numerical model. This is achieved by the development of the unknown displacement vector on the basis of the eigenmodes; a particular attention is paid to the calculation of the nonlinear stiffness coefficients of the model. The method combines the stochastic finite element methods with a modal reduction class based on sub-structuring the component mode synthesis method. The reference method is the Monte Carlo simulation which consists in making several simulations for different values of the uncertain parameters. The simulation of complex and nonlinear structures is costly in terms of memory and computation time. To solve this problem, the perturbation method combined with the component mode synthesis reduction method significantly reduces the computational cost by preserving the physical content of the original structure. The numerical integration by the Newmark schema is used; the first statistical moments (mean and variance) of the nonlinear dynamic response are computed. Numerical simulations illustrate the accuracy and effectiveness of the proposed methodology.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer and are now the backbone of therapy for several malignancies. However, ICIs can cause a spectrum of kidney immune-related adverse events including acute kidney injury (AKI), most commonly manifesting as acute interstitial nephritis (AIN), although glomerular disease and electrolyte disturbances have also been reported. In this position statement by the American Society of Onco-nephrology (ASON), we summarize the incidence and risk factors for ICI-AKI, pathophysiological mechanisms, and clinicopathologic features of ICI-AKI. We also discuss novel diagnostic approaches and promising biomarkers for ICI-AKI. From expert panel consensus, we provide clinical practice points for the initial assessment and diagnosis of ICI-AKI, management and immunosuppressive therapy, and consideration for rechallenge with ICI following AKI episodes. In addition, we explore ICI use in special populations, such as kidney transplant recipients, and propose key areas of focus for future research and clinical investigation., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Accurate assessment of GFR is crucial to guiding drug eligibility, dosing of systemic therapy, and minimizing the risks of both undertreatment and toxicity in patients with cancer. Up to 32% of patients with cancer have baseline CKD, and both malignancy and treatment may cause kidney injury and subsequent CKD. To date, there has been lack of guidance to standardize approaches to GFR estimation in the cancer population. In this two-part statement from the American Society of Onco-Nephrology, we present key messages for estimation of GFR in patients with cancer, including the choice of GFR estimating equation, use of race and body surface area adjustment, and anticancer drug dose-adjustment in the setting of CKD. These key messages are based on a systematic review of studies assessing GFR estimating equations using serum creatinine and cystatin C in patients with cancer, against a measured GFR comparator. The preponderance of current data involving validated GFR estimating equations involves the CKD Epidemiology Collaboration (CKD-EPI) equations, with 2508 patients in whom CKD-EPI using serum creatinine and cystatin C was assessed (eight studies) and 15,349 in whom CKD-EPI with serum creatinine was assessed (22 studies). The former may have improved performance metrics and be less susceptible to shortfalls of eGFR using serum creatinine alone. Since included studies were moderate quality or lower, the American Society of Onco-Nephrology Position Committee rated the certainty of evidence as low. Additional studies are needed to assess the accuracy of other validated eGFR equations in patients with cancer. Given the importance of accurate and timely eGFR assessment, we advocate for the use of validated GFR estimating equations incorporating both serum creatinine and cystatin C in patients with cancer. Measurement of GFR via exogenous filtration markers should be considered in patients with cancer for whom eGFR results in borderline eligibility for therapies or clinical trials., (Copyright © 2024 by the American Society of Nephrology.)

Intracellular phosphate is critical for cellular processes such as signaling, nucleic acid synthesis, and membrane function. Extracellular phosphate (Pi) is an important component of the skeleton. Normal levels of serum phosphate are maintained by the coordinated actions of 1,25-dihydroxyvitamin D3, parathyroid hormone and fibroblast growth factor-23, which intersect in the proximal tubule to control the reabsorption of phosphate via the sodium-phosphate cotransporters Npt2a and Npt2c. Furthermore, 1,25-dihydroxyvitamin D3 participates in the regulation of dietary phosphate absorption in the small intestine. Clinical manifestations associated with abnormal serum phosphate levels are common and occur as a result of genetic or acquired conditions affecting phosphate homeostasis. For example, chronic hypophosphatemia leads to osteomalacia in adults and rickets in children. Acute severe hypophosphatemia can affect multiple organs leading to rhabdomyolysis, respiratory dysfunction, and hemolysis. Patients with impaired kidney function, such as those with advanced CKD, have high prevalence of hyperphosphatemia, with approximately two-thirds of patients on chronic hemodialysis in the United States having serum phosphate levels above the recommended goal of 5.5 mg/dL, a cutoff associated with excess risk of cardiovascular complications. Furthermore, patients with advanced kidney disease and hyperphosphatemia (>6.5 mg/dL) have almost one-third excess risk of death than those with phosphate levels between 2.4 and 6.5 mg/dL. Given the complex mechanisms that regulate phosphate levels, the interventions to treat the various diseases associated with hypophosphatemia or hyperphosphatemia rely on the understanding of the underlying pathobiological mechanisms governing each patient condition., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Cause-specific death rates are rarely available to guide health interventions for adults in South Asia. We report mortality patterns among Karachi's urban poor., Methods: We conducted verbal autopsies for adult deaths under active surveillance during 1990-1993 in five urban slums of Karachi. Two physicians assigned underlying cause of death by consensus. Analysis included cause- and category-specific rates, 45Q15s and comparison with 1991 Japanese national statistics., Results: All 345 adult deaths (15-59 years) in the 5 slums (total population 45,389) were included. Male mortality exceeded female (4.4 vs 3.3/1000, p = .02). Noncommunicable diseases claimed 59% of deaths, communicable and reproductive 27% and injuries, 15%. The leading identified death rates (/100,000) among women were: circulatory disorders (66), maternal causes (33), tuberculosis (30), and burns (23); and among men they were: circulatory disorders (124) tuberculosis (30) and road traffic accidents (30). Overall Karachi adult mortality was 3.7 times Japanese rate. Compared to Japan, adults in Karachi had one to two orders of magnitude excess mortality due to maternal causes, tuberculosis and burns. Circulatory disorders and tuberculosis accounted for 47% of excess male mortality; these plus maternal causes and burns accounted for 55% of excess female mortality., Conclusion: These mortality levels and patterns compel interventions and research for poor urban adults beyond maternal health. Women's health would equally benefit from tuberculosis control or burn prevention. Men need safer travel. Both need improved cardiovascular health.