Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

About microcracking due to leaching in cementitious composites: X-ray microtomography description and numerical approach

Chemical shock of cement based materials leads to significant degradation of their physical properties. A typical scenario is a calcium leaching due to water (water with very low pH compared with that of pore fluid). The main objective of this paper is to evaluate the evolution of microstructure induced by leaching of a cementitious composite using synchrotron X-ray micro tomography, mainly from an experimental point of view. In this particular case, it was possible to identify cracking induced by leaching. After a description of the degradation mechanism and the X-ray synchrotron microtomographic analysis, numerical simulations are performed in order to show that cracking is induced by an initial pre-stressing of the composite, coupled with decalcification shrinkage and dramatic decrease in tensile strength during leaching. X-ray microtomography analysis allowed to make evidence of an induced microcracking in cementitious material submitted to leaching

Small Landers and Separable Sub-Spacecraft for Near-term Solar Sails

Following the successful PHILAE landing with ESA's ROSETTA probe and the launch of the MINERVA rovers and the Mobile Asteroid Surface Scout, MASCOT, aboard the JAXA space probe, HAYABUSA2, to asteroid (162173) Ryugu, small landers have found increasing interest. Integrated at the instrument level in their mothership they support small solar system body studies. With efficient capabilities, resource-friendly design and inherent robustness they are an attractive exploration mission element. We discuss advantages and constraints of small sub-spacecraft, focusing on emerging areas of activity such as asteroid diversity studies, planetary defence, and asteroid mining, on the background of our projects PHILAE, MASCOT, MASCOT2, the JAXA-DLR Solar Power Sail Lander Design Study, and others. The GOSSAMER-1 solar sail deployment concept also involves independent separable sub-spacecraft operating synchronized to deploy the sail. Small spacecraft require big changes in the way we do things and occasionally a little more effort than would be anticipated based on a traditional large spacecraft approach. In a Constraints-Driven Engineering environment we apply Concurrent Design and Engineering (CD/CE), Concurrent Assembly, Integration and Verification (CAIV) and Model-Based Systems Engineering (MBSE). Near-term solar sails will likely be small spacecraft which we expect to harmonize well with nano-scale separable instrument payload packages

The PINK1 p.I368N mutation affects protein stability and ubiquitin kinase activity

Abstract Background Mutations in PINK1 and PARKIN are the most common causes of recessive early-onset Parkinson’s disease (EOPD). Together, the mitochondrial ubiquitin (Ub) kinase PINK1 and the cytosolic E3 Ub ligase PARKIN direct a complex regulated, sequential mitochondrial quality control. Thereby, damaged mitochondria are identified and targeted to degradation in order to prevent their accumulation and eventually cell death. Homozygous or compound heterozygous loss of either gene function disrupts this protective pathway, though at different steps and by distinct mechanisms. While structure and function of PARKIN variants have been well studied, PINK1 mutations remain poorly characterized, in particular under endogenous conditions. A better understanding of the exact molecular pathogenic mechanisms underlying the pathogenicity is crucial for rational drug design in the future. Methods Here, we characterized the pathogenicity of the PINK1 p.I368N mutation on the clinical and genetic as well as on the structural and functional level in patients’ fibroblasts and in cell-based, biochemical assays. Results Under endogenous conditions, PINK1 p.I368N is expressed, imported, and N-terminally processed in healthy mitochondria similar to PINK1 wild type (WT). Upon mitochondrial damage, however, full-length PINK1 p.I368N is not sufficiently stabilized on the outer mitochondrial membrane (OMM) resulting in loss of mitochondrial quality control. We found that binding of PINK1 p.I368N to the co-chaperone complex HSP90/CDC37 is reduced and stress-induced interaction with TOM40 of the mitochondrial protein import machinery is abolished. Analysis of a structural PINK1 p.I368N model additionally suggested impairments of Ub kinase activity as the ATP-binding pocket was found deformed and the substrate Ub was slightly misaligned within the active site of the kinase. Functional assays confirmed the lack of Ub kinase activity. Conclusions Here we demonstrated that mutant PINK1 p.I368N can not be stabilized on the OMM upon mitochondrial stress and due to conformational changes in the active site does not exert kinase activity towards Ub. In patients’ fibroblasts, biochemical assays and by structural analyses, we unraveled two pathomechanisms that lead to loss of function upon mutation of p.I368N and highlight potential strategies for future drug development

Feasibility-Study OOS-RAV

With the objective of designing a mission to validate the DEOS robotic arm, a CE study named OOS-RAV (On Orbit Servicing– Robotic Arm Verification) was conducted. The defined mission was to approach a target satellite (either one already in orbit or a target satellite specifically designed and carried along with our spacecraft), and in close distances to grab it with the robotic arm. The CE study for OOS-RAV took place from 4th to 8th May 2015 in the Concurrent Engineering Facility of the DLR Bremen. The domains were occupied by members of various DLR sites depending on their expertise

Dependence on External Finance: An Inherent Industry Characteristic?

Rajan and Zingales (1998) use U.S. Compustat firm data for the 1980s to obtain measures of manufacturing sectors? Dependence on External Finance (DEF). They take any differences in these measures to be structural/technological and thus applicable to other countries. Their joint assumptions about how to obtain representative values of DEF by sector and about why these values differ fundamentally between sectors have been adopted in additional studies seeking to show that sectors benefit unequally from a country?s level of financial development. However, the assumptions as such have not been examined. The present study, conducted with cyclically adjusted annual measures of DEF derived from U.S. industry data for 1977-1997, attempts to do so using data that are aggregated by sector. We find that those variables that may be regarded as structural/ technological have very low explanatory power, and that the DEF figures calculated from micro data do not correspond closely to what is obtained from aggregate figures. Hence key assumptions on which RZ's argumentation is based could not be validated