3510-V 390-m Omega . cm(2) 4H-SiC Lateral JFET on a Semi-Insulating Substrate

The performance of high-voltage 4H-SiC lateral JFETs on a semi-insulating substrate is reported in this letter. The design of the voltage-supporting layers is based on the charge compensation of p- and n-type epilayers. The best measured breakdown voltage is 3510 V, which, to the authors\u27 knowledge, is the highest value ever reported for SiC lateral switching devices. The R-on of this device is 390 m Omega . cm(2), in which 61% is due to the drift-region resistance. The BV2/R-on is 32 MW/cm(2), which is typical among other reported SiC lateral devices

Chromosome segregation in Archaea : SegA– and SegB–DNA complex structures provide insights into segrosome assembly

Genome segregation is a vital process in all organisms. Chromosome partitioning remains obscure in Archaea, the third domain of life. Here, we investigated the SegAB system from Sulfolobus solfataricus. SegA is a ParA Walker-type ATPase and SegB is a site-specific DNA-binding protein. We determined the structures of both proteins and those of SegA–DNA and SegB–DNA complexes. The SegA structure revealed an atypical, novel non-sandwich dimer that binds DNA either in the presence or in the absence of ATP. The SegB structure disclosed a ribbon–helix–helix motif through which the protein binds DNA site specifically. The association of multiple interacting SegB dimers with the DNA results in a higher order chromatin-like structure. The unstructured SegB N-terminus plays an essential catalytic role in stimulating SegA ATPase activity and an architectural regulatory role in segrosome (SegA–SegB–DNA) formation. Electron microscopy results also provide a compact ring-like segrosome structure related to chromosome organization. These findings contribute a novel mechanistic perspective on archaeal chromosome segregation

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Cyclic Stability of Locking Plate Augmented with Intramedullary Polymethyl Methacrylate (PMMA) Strut Fixation for Osteoporotic Humeral Fractures: A Biomechanical Study

The locking plate may provide improved fixation in osteoporotic bone; however, it has been reported to fail due to varus collapse or screw perforation of the articular surface, especially in osteoporotic bone with medial cortex comminution. Using bone graft as an intramedullary strut together with plate fixation may result in a stronger construct. However, the drawbacks of bone grafts include limited supply, high cost, and infection risk. PMMA (so-called bone cement) has been widely used for implant fixation due to its good mechanical properties, fabricability, and biocompatibility. The risk of donor-site infection and the drawbacks of allografting may be overcome by considering PMMA struts as alternatives to fibular grafts for humeral intramedullary grafting surgeries. However, the potential effects of intramedullary PMMA strut on the dynamic behaviour of osteoporotic humerus fractures remain unclear. This study aimed to investigate the influence of an intramedullary PMMA strut on the stability of unstable proximal humeral fractures in an osteoporotic synthetic model. Two fixation techniques, a locking plate alone (non-strut group) and the same fixation augmented with an intramedullary PMMA strut (with-strut group), were cyclically tested in 20 artificial humeral models. Axially cyclic testing was performed to 450 N for 10,000 cycles, intercyclic motion, cumulated fragment migration, and residual deformation of the constructs were determined at periodic cyclic intervals, and the groups were compared. Results showed that adding an intramedullary PMMA strut could decrease 1.6 times intercyclic motion, 2 times cumulated fracture gap migration, and 1.8 times residual deformation from non-strut fixation. During cycling, neither screw pull-out, cut-through, nor implant failure was observed in the strut-augmented group. We concluded that the plate-strut mechanism could enhance the cyclic stability of the fixation and minimize the residual displacement of the fragment in treating osteoporotic proximal humeral unstable fractures. The PMMA strut has the potential to substitute donor bone and serve as an intramedullary support when used in combination with locking plate fixation. The intramedullary support with bone cement can be considered a solution in the treatment of osteoporotic proximal humeral fractures, especially when there is medial comminution

Metastatic Urothelial Carcinoma of the Bladder with Lymph Node-only Metastasis Treated with M-VAC (Methotrexate, Vinblastine, Doxorubicin and Cisplatin) has a Better Survival than GC (Gemcitabine and Cisplatin)

Background: Previous studies demonstrated that GC (gemcitabine and cisplatin) provided a similar survival advantage as M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for urothelial carcinoma of the bladder (UCB), and had a better safety profile and improved tolerability. However, no clinical clues in selection of first-line chemotherapy regimen were suggested. This study aims to determine whether different sites of metastasis and chemotherapy regimens affected the prognosis of patients with metastatic UCB. Methods: Patients with metastatic UCB were retrospectively reviewed. Data on clinical characteristics, progression free survival (PFS), overall survival (OS), overall response rate (ORR) and complete response (CR) rate were analyzed. Results: Between 2000 and 2012, a total of 76 patients with metastatic UCB were enrolled. The median age was 64.5 years and the median follow-up period was 13.6 months. Of these patients, 37 had lymph node-only metastasis (LOM) and 39 had non-LOM. The median survival was significantly longer for UCB patients with LOM. The median PFS was 10.0 months for LOM and 4.3 months for non-LOM (P = < 0.01), while the median OS was 16.9 months for LOM and 10.5 months for non-LOM (P = < 0.01). The ORR and CR rate were both significantly higher in patients with LOM than in those with non-LOM. Subgroup analysis suggested that UCB patients with LOM treated with M-VAC had a better survival. The median PFS was 16.4 months in the M-VAC group and 8.7 months in the GC group (P = 0.08), while the median OS was 23.1 months in the M-VAC group and 16.0 months in the GC group (P = 0.03). The CR rate remained significant. Conclusions: UCB patients with LOM, especially those treated with M-VAC, had better survival outcomes and greater CR rate than those with non-LOM. However, the sample size of this study was quite small and analyzed on a retrospective basis. Further prospective randomized studies are warranted

Biomechanical Effect of Hybrid Dynamic Stabilization Implant on the Segmental Motion and Intradiscal Pressure in Human Lumbar Spine

The hybrid dynamic stabilization system, Dynesys-Transition-Optima, represents a novel pedicle-based construct for the treatment of lumbar degenerative disease. The theoretical advantage of this system is to stabilize the treated segment and preserve the range of motion within the adjacent segment while potentially decreasing the risk of adjacent segment disease following lumbar arthrodesis. Satisfactory short-term outcomes were previously demonstrated in the Dynesys-Transition-Optima system. However, long-term follow-up reported accelerated degeneration of adjacent segments and segmental instability above the fusion level. This study investigated the biomechanical effects of the Dynesys-Transition-Optima system on segment motion and intradiscal pressure at adjacent and implanted levels. Segmental range of motion and intradiscal pressure were evaluated under the conditions of the intact spine, with a static fixator at L4–5, and implanted with DTO at L3–4 (Dynesys fixator) and L4–5 (static fixator) by applying the loading conditions of flexion/extension (±7.5 Nm) and lateral bending (±7.5 Nm), with/without a follower preload of 500 N. Our results showed that the hybrid Dynesys-Transition-Optima system can significantly reduce the ROM at the fusion level (L4–L5), whereas the range of motion at the adjacent level (L3–4) significantly increased. The increase in physiological loading could be an important factor in the increment of IDP at the intervertebral discs at the lumbar spine. The Dynesys-Transition-Optima system can preserve the mobility of the stabilized segments with a lesser range of motion on the transition segment; it may help to prevent the occurrence of adjacent segment degeneration. However, the current study cannot cover all the issues of adjacent segmental diseases. Future investigations of large-scale and long-term follow-ups are needed