Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell ...therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM).
This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m
. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 10
cells/kg range, 0.07 to 2.1 × 10
) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group.
At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval CI, 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached.
LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM.
ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.
Sierra Leone launched the Free Health Care Initiative, which abolished health user fees for pregnant and breastfeeding women and children under five years of age, in 2010. Combining data from the ...Demographic and Health Survey and a geocoded dataset for the distribution of public health facilities, I design a difference-in-differences study involving birth timing and transportation cost to investigate its impact on infant mortality and desired fertility. I find that the program does not achieve its goal of reducing infant mortality, with the lack of vaccination being a major problem. Notwithstanding the lack of reduction in infant mortality, the program leads to a significant decline in desired fertility, implying that parents may overestimate the program's benefits and change their expectations of infant mortality accordingly. Heterogeneous effects by household wealth suggest that poor households are more adversely affected by the program than wealthy ones.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
Many countries have undertaken large and high-profile payment-for-ecosystem-services (PES) programs to sustain the use of their natural resources. Nevertheless, few studies have ...comprehensively examined the impacts of existing PES programs. Grassland Ecological Compensation Policy (GECP) is one of the few pastorally focused PES programs with large investments and long duration, which aim to improve grassland quality and increase herder income. Here we present empirical evidence of the effects of GECP on grassland quality and herder income. Through a thorough and in-depth econometric analysis of remote sensing and household survey data, we find that, although GECP improves grassland quality (albeit to only a small extent) and has a large positive effect on income, it exacerbates existing income inequality among herders within their local communities. The analysis demonstrates that the program has induced herders to change their livestock production behavior. Heterogeneity analysis emphasizes the importance of making sure the programs are flexible and are adapted to local resource circumstances.
Increasing studies approach translation from alternative aspects, either borrowing different methodologies or concepts from other disciplines. These various attempts have expanded the field of ...translation studies to a broader area with a focus on either intercultural studies or the translator’s studies. Howard Goldblatt, as a respected translator in China, has provided limitless insights into Chinese literature in translation. Recent studies are moving closer to the specific traits of the translator, and this study thus focuses on Goldblatt’s translation of Red Sorghum, as the original work boasts plenty of cultural words, regional dialects, and colloquialisms. The purpose of this study is to determine Goldblatt’s translation tendency, the corresponding translation methods he adopted, as well as the reasons behind correspondent behaviors and choices. To answer the above inquiries, quantitative and qualitative methods will be jointly adopted. Multiple factors leading to the translator’s visibility and invisibility are also analyzed with reference to the quantitative results.
Plain language summary
This research demonstrates a renewed interest in “translator’s invisibility”, a concept proposed by Lawrence Venuti in 2001, through heightening its long neglected opposing aspect of “translator’s visibility”. This article has reexamined disputed viewpoints on Goldblatt’s translation tendency with solid evidence and extended the discussion on foreignization and domestication by substantiating them with specific instructive translation methods. This article has also discussed in greater detail how the translator grapples with fidelity and readability, the author and the market while making compromises when the two aspects conflict. It is hoped that this research may shed insights into trending research on translator’s studies and the ongoing discussion on Venuti’s domestication and foreignization in the particular area of literary translation. It is also hoped to benefit the production of translation in literature and help promote effective cultural exchange and cross-cultural communication.
Whether creativity can be taught or not has remained an unresolved and recurring topic of debate in creative writing. Writing that is creative and imaginative is distinguished from translation, which ...is more derivative. However, both activities are creative in their own unique ways. With the intent of fostering creativity in creative writing, I wish to explore the following questions in this paper: Where does translation's creativity come from? Can creativity be facilitated by the opposing forces of derivation and deviation in translation? If so, how exactly? How can a creative pedagogy be based on such disparate elements? In this essay, I argue that the contradictory characteristic of translation being both derivative and derived is consistent with a certain aspect of creativity, making it useful for creative writing. Then, I will propose a translation-based creative pedagogy while examining works from my poetry project that incorporate the practice of translation.
While China's wind power initiative has experienced rapid growth, serious curtailment issues persist. Though some studies have investigated this matter, we explain this phenomenon from the novel ...perspective of excess capacity. We first set up a theoretical model to explore the mechanism behind excess investment and find that the ‘sticky’ feed-in tariff (FIT) and declining costs of wind power generate high mark-up for wind power investors, leading to a higher probability of excessive investment. The theoretical prediction is empirically tested with a probit and tobit model using provincial-level data between 2009 and 2016. The estimation results show that a 0.1 yuan increase in the mark-up leads to a 2%–3% increase in the rate of curtailed wind power. Based on the estimation results, we simulate several scenarios to assess quantitatively how an improved policy design could have alleviated the curtailment issue. Simply increasing the frequency of the FIT rate adjustment while maintaining the same subsidy reduction level between 2009 and 2016 could have reduced the curtailed wind power by 23 to 27 billion kwh, accounting for 15%–17% of actual curtailed wind power. If the policy were better designed to reflect the declining trend of wind power costs more accurately, the curtailment rates could have been further reduced by 2.81%, corresponding to a reduction in wasted wind energy of >43 billion kwh (or 28% of actual curtailment). Although accepting curtailment for a certain period could help to accelerate renewable energy deployment, our analysis shows that the FIT policy design could have been improved to reduce welfare loss. These findings can not only assist the Chinese government in framing effective policies, but also may be applied to other emerging technologies or industries that require subsidy support.
•Wind power in China has experienced rapid growth, but curtailment issues persist•The sticky feed-in tariff (FIT) together with the declining costs of wind power generate high markup for wind power investors and leads to excessive investment.•An increase in the markup by 0.1 yuan leads to an increase in the rate of curtailed wind power by 2–3%.•A better-designed policy could have reduced wasted wind energy by 28%
Background LCAR-B38M is a chimeric antigen receptor T cell product with two binding domains targeting B cell maturation antigen. Our previous reports showed a remarkable efficacy of LCAR-B38M in ...patients with relapsed/refractory multiple myeloma (RRMM) at a median follow-up of 2 years. Here, we report long-term safety and efficacy data from a median follow-up of 4 years. Methods LEGEND-2 was a phase 1, single-arm, open-label study conducted in four registered sites in China. Seventy-four participants with RRMM received LCAR-B38M treatment. Lymphodepletion was performed using cyclophosphamide or cyclophosphamide plus fludarabine. LCAR-B38M, at a median dose of 0.513 x 10.sup.6 cells/kg, was intravenously administered either in three split infusions or in a single infusion. The primary objective was the safety of LCAR-B38M, and the secondary objective was efficacy. Results As of May 25, 2021, the median follow-up was 47.8 months. All patients experienced greater than or equal to 1 adverse events (AEs). Grade greater than or equal to 3 AEs were observed in 45/74 (60.8%) patients. Cytokine release syndrome (CRS) occurred in 68/74 (91.9%) cases; 7 (9.5%) had grade greater than or equal to 3 CRS. One patient experienced grade 1 central nervous system toxicity. The overall response rate was 87.8%. Fifty-four out of 74 (73.0%) patients achieved complete response. The median progression-free survival was 18.0 months, and the median overall survival for all patients was not reached. The median duration of response was 23.3 months. Four patients experienced viral infection more than 6 months post-infusion, and four patients developed second primary non-hematological malignancies at a median time of 11.5 months post-CAR-T cell transfer. Conclusions The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. Trial registration Clinicaltrials.gov NCT03090659 (retrospectively registered on March 27, 2017); ChiCTR-ONH-17012285. Keywords: Multiple myeloma, Chimeric antigen receptor therapy, B cell maturation antigen, Safety, Efficacy
We apply a partial adjustment model to investigate the driving factors of the regional disparity of China's wind power development. We have three major findings. First, similar to many industries, ...wind power shows an agglomeration effect, that is, existing installed capacity attracts new addition of capacity. Second, demand factors including both local demand, indicated by variables in the local economy, and demand outside the region, indicated by transmission capacity, do not significantly affect the location choice of wind power farms. Lastly, governmental supporting measures have heterogeneous effects on different regions. They are most effective in wind resource rich regions but have little impact in other regions.
•A partial adjustment model to investigate the driving factors of the regional disparity of China's wind power development•Demand factors do not significantly affect the location choice of wind power farms.•Governmental supporting measures have heterogeneous effects on different regions.
There was much evidence suggesting that the serum lactate dehydrogenase (LDH) levels reflect the extent of various pathophysiological processes. However, the current information about dynamic change ...of LDH in COVID-19 pneumonia has not been well investigated.
Study was performed in 87 cases confirmed by COVID-19 infection. The serum LDH levels were determined at diagnosis and follow-up visits. The evaluation of clinical response to therapy was based on chest CT scan. We selected the value of LDH around the data of chest CT scan (- 1 ~ + 1 day).
At diagnosis, significant differences in LDH levels were found between non-severe and severe group (P < 0.05). It was demonstrated that increase or decrease of LDH was indicative of radiographic progress or improvement (P < 0.05). The time to LDH normalization (5.67 ± 0.55, days) was positively correlated with the time to radiographic absorption (5.57 ± 0.65 days, r = 0.53, P < 0.05). Applying the cut-off value of the increase in LDH has good specificity to predict disease progression.
Serum LDH was validated for its potential usefulness as markers for evaluating clinical severity and monitoring treatment response in COVID-19 pneumonia.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Effect of strains CL-1 and X30 on Cd immobilization and uptake of rape was evaluated.•CL-1 and X30 increased pH and immobilized Cd in the solution and rhizosphere soil.•CL-1 and X30 increased ...polyamine concentration in the solution and rhizosphere soil.•CL-1 was better to increase arginine decarboxylase-producing bacteria in the soil.•CL-1 was better to decrease the rhizosphere soil available Cd and rapeseed Cd uptake.
Two Cd-immobilizing and polyamine-producing bacteria Serratia liquefaciens CL-1 and Bacillus thuringiensis X30 were characterized for their effects on Cd immobilization, pH, and polyamine production in the solution and the rapeseed biomass and Cd uptake of Brassica napus Qinyou-10 in Cd-contaminated soil. These strains significantly increased pH and reduced water-soluble Cd concentration (25–76%) compared to the controls. Furthermore, strain CL-1 produced more polyamine (71–192%) in the solution than strain X30. Cell surface absorbed Cd content was increased by 23-56% in the presence of strain CL-1 compared to strain X30. The strains significantly increased the rapeseed biomass (12–32%), pH, polyamine content (70–244%), and relative abundance (21-49%) of arginine decarboxylase-producing bacteria (ADPB) of the rhizosphere soils but decreased DTPA-extractable Cd content and rapeseed Cd uptake compared to the controls. Notably, strain CL-1 had higher ability to reduce the rapeseed Cd and DTPA-extractable Cd contents and increase the abundance of ADPB than strain X30. Our results showed the distinct impact of these strains on the rapeseed Cd uptake and available Cd content and suggested that these strains reduced the available Cd and rapeseed Cd uptake by increasing the cell adsorption of Cd, abundance of ADPB, polyamine production, and pH in the rhizosphere soils.
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