Search

Purpose: Quality-adjusted life-year (QALY) is a dominant measurement of health gain in economic evaluations for pricing drugs. However, end-of-life (EoL) patients' preference for QALY gains in life expectancy (LE) and quality of life (QoL) during different disease stages remains unknown and is seldom involved in decision-making. This study aims to measure preferences and willingness-to-pay (WTP) towards different types of QALY gain among EoL cancer patients. Methods: We attributed QALY gain to four types, gain in LE and QoL, respectively, and during both progression-free survival (PFS) and post-progression survival (PPS). A discrete choice experiment including five attributes (the four QALY attributes and one cost attribute) with three levels each was developed and conducted with 85 Chinese advanced non-small cell lung cancer patients in 2022. All levels were set with QALY gain/cost synthesised from research on anti-lung cancer drugs recently listed by Chinese National Healthcare Security Administration. Each respondent answered six choice tasks in a face-to-face interview. The data were analysed using mixed logit models. Results: Patients valued LE-related QALY gain in PFS most, with a relative importance of 81.8% and a WTP of $43,160 [95% CI 26,751 ~ 59,569] per QALY gain. Respondents consistently preferred LE-related to QoL-related QALY gain regardless of disease stage. Patients with higher income or lower education levels tended to pay more for QoL-related QALY gain. Conclusion: Our findings suggest a prioritised resource allocation to EoL-prolonging health technologies. Given the small sample size and large individual heterogeneity, a full-scale study is needed to provide more robust results. [ABSTRACT FROM AUTHOR]

As a typical contaminant in fossil fuels, vanadium has undergone dramatically increase due to the impacts from human activities. The excessive anthropogenic vanadium emissions have altered natural geochemical processes. However, research on vanadium geochemistry in the ocean, which is the major sink for vanadium mobilized on land, has lagged much behind relative to those of other contaminants. Here we reconstruct historical patterns of vanadium in surface seawater utilizing a high-resolution temporal record (1984–2015 CE) of geochemical proxies (vanadium/calcium (V/Ca), δ18O, δ13C, etc.) in a Porites coral colony from an offshore non-estuarine island in the northern South China Sea (SCS). We find a close association between the surface winds and the temporal patterns of coral V/Ca ratios, revealing great potential for documenting prehistoric changes in tropical cyclones. Moreover, the coral V/Ca record remarkably captured the temporal patterns of anthropogenic activities, offering a valuable and novel tool for testing the efficacy of specific legislation on pollution prevention. Combined with the other reported coral vanadium data, we recovered the historical changes in vanadium emissions in the northern SCS and identified that changing industrial practices should be responsible for the differences in anthropogenic vanadium emissions at each stage. Our results demonstrated that the coral V/Ca ratio at a high temporal resolution has great potential as a new and direct geochemical proxy for tropical cyclones after removing artificial disturbances in the ocean. [ABSTRACT FROM AUTHOR]

Background: Tuberculous peritonitis is the most common form of extrapulmonary tuberculosis infection in peritoneal dialysis patients. However, diagnosing tuberculous peritonitis quickly and early has always been a challenge for nephrologists. Mycobacterium tuberculosis antigen-specific gamma interferon enzyme-linked immunospot (IFN-γ ELISPOT) assay has been widely used in the clinical diagnosis of tuberculous pleurisy and peritonitis, but its use has not been reported for uremia. Methods: This study mainly verified the feasibility of using the M. tuberculosis antigen-specific IFN-γ ELISPOT assay in the diagnosis of continuous ambulatory peritoneal dialysis (CAPD) patients with tuberculous peritonitis. Taking M. tuberculosis culture as the gold standard, the IFN-γ ELISPOT assay was used to analyze peripheral blood and peritoneal dialysis fluid of patients, and the receiver operating characteristic (ROC) curves in patients with tuberculous peritonitis (TBP) or non-tuberculous peritonitis (NTBP) were analyzed. Results: The area under the receiver operating characteristic curve (AUC) was 0.927 (95% CI 0.816–1.000, P = 0.001) for the ELISPOT assay with peritoneal fluid mononuclear cells (PFMC), which was higher than that for the ELISPOT assay with peripheral blood mononuclear cells (PBMC) (0.825, 95% CI 0.6490–1.000, P = 0.011). The cutoff value for the diagnosis of TBP was 40 spot-forming cells (SFCs)/2 × 105 for the ELISPOT with PBMC, with a sensitivity of 55.6%, a specificity of 92.3%, and a diagnostic efficiency of 77.3%. The cutoff value for the diagnosis of TBP was 100 SFCs/2 × 105 for the ELISPOT on PFMC, with a sensitivity, specificity, and diagnostic efficiency 77.8%, 84.6%, and 81.8%, respectively. Parallel and serial testing algorithms appeared more accurate than single ELISPOT assays with PBMC, but ELISPOT assays with PFMC. Conclusions: The IFN-γ release test can be used for the early diagnosis of CAPD-related TBP; compared with peripheral blood, peritoneal fluid may be a more effective and accurate medium to diagnose CAPD complicated with tuberculous peritonitis. [ABSTRACT FROM AUTHOR]

The transitional area between the northeastern margin of the Qinghai-Tibetan Plateau, Ordos Block and Alxa Block, also being the northern segment of the North-South Seismic Belt, is characterized by considerably high seismicity level and high risk of strong earthquakes. In view of the special tectonic environment and deep tectonic setting in this area, this study used two seismic wide-angle reflection/refraction cross profiles for double constraining, so as to more reliably obtain the fine-scale velocity structure characteristics in both the shallow and deep crust of individual blocks and their boundaries in the study area, and further discuss the seismogenic environment in seismic zones with strong historical earthquakes. In this paper, the P-wave data from the two profiles are processed and interpreted, and two-dimensional crustal velocity structure models along the two profiles are constructed by travel time forward modeling. The results show that there are great differences in velocity structure, shape of intra-crustal interfaces and crustal thickness among different blocks sampled by the two seismic profiles. The crustal thickness along the Lanzhou-Huianbu-Yulin seismic sounding profile (L1) increases from ∼43 km in the western margin of Ordos Block to ∼56 km in the Qilian Block to the west. In the Ordos Block, the velocity contours vary gently, and the average velocity of the crust is about 6.30 km s−1; On the other hand, the velocity structures in the crust of the Qilian Block and the arclike tectonic zone vary dramatically, and the average crustal velocities in these areas are about 0.10 km s−1 lower than that of the Ordos Block. In addition, discontinuous low-velocity bodies (LVZ1 and LVZ2) are identified in the crust of the Qilian Block and the arc-like tectonic zone, the velocity of which is 0.10-0.20 km s−1 lower than that of the surroundings. The average crustal thickness of the Ordos Block is consistently estimated to be around 43 km along both Profile L2 (Tongchuan-Huianbu-Alashan left banner seismic sounding profile) and Profile L1. In contrast to the gently varying intra-crustal interfaces and velocity contours in the Ordos Block along Profile L1, which is a typical structure characteristic of stable cratons, the crustal structure in the Ordos Block along Profile L2 exhibits rather complex variations. This indicates the presence of significant structural differences in the crust within the Ordos Block. The crustal structure of the Helan Mountain Qilian Block and the Yinchuan Basin is featured by “uplift and depression” undulations, showing the characteristics of localized compressional deformation. Moreover, there are low-velocity zones with alternative high and low velocities in the middle and lower crust beneath the Helan Mountain, where the velocity is about 0.15-0.25 km s−1 lower than that of the surrounding areas. The crustal thickness of the Alxa Block is about 49 km, and the velocity contours in the upper and middle-lower crust of the block vary significantly. The complex crustal velocity structure images along the two seismic sounding profiles L1 and L2 reveal considerable structural differences among different tectonic blocks, their coupling relationships and velocity structural features in the seismic zones where strong historical earthquakes occurred. The imaging result of this study provides fine-scale crustal structure information for further understanding the seismogenic environment and mechanism in the study area. [ABSTRACT FROM AUTHOR]

Prenatal ethanol exposure can cause extensive apoptotic neurodegeneration throughout the developing central nervous system (CNS), which results in cognitive deficits and memory decline. However, the underlying mechanisms need further study. Single-minded 2 (Sim2), a transcriptional repressor, is reportedly involved in diseases that impair learning and memory, such as Down syndrome (DS) and Alzheimer's disease. It is still unknown whether Sim2 is involved in regulating ethanol-mediated neuronal injury that might ultimately lead to neuronal dysfunction and subsequent learning and memory deficits. To study the effects of ethanol on Sim2 expression and neuronal injury, we used animal models and cell culture experiments. Our results indicated that in SH-SY5Y cells, ethanol exposure increased Sim2 expression and levels of cleaved caspase 3, which is a marker for cells undergoing apoptosis. Silencing Sim2 expression attenuated caspase 3 activation and cellular apoptosis. We also found that protein kinase A (PKA) activation induced Sim2 expression, as did ethanol. Inhibiting the PKA signaling pathway with H-89 decreased Sim2 expression and cleavage of caspase 3 that was induced by ethanol in vivo and in vitro. We further found that PKA regulated Sim2 expression at the transcriptional level. These results demonstrate that ethanol leads to increased Sim2 expression via the PKA pathway, ultimately resulting in apoptotic cell death. [ABSTRACT FROM AUTHOR]

The compression behavior of Ni77P23 amorphous alloy is investigated at room temperature in a diamond-anvil cell instrument using in-situ high pressure energy dispersive X-ray diffraction with a synchrotron radiation source, The equation of state is determined by fitting the experimental data according to Birch-Murnaghan equation: -ΔV/V0=0.08606P-3.2×10-4P²+5.7×10-6P³. It is found that the structure of Ni77P23 amorphous alloy is stable under pressures up to 30.5 GPa. [ABSTRACT FROM AUTHOR]