The differential effects of tumor burdens on predicting the net benefits of ssCART-19 cell treatment on r/r B-ALL patients

The tumor burden (TB) is significantly related to the severity of cytokine release syndrome (CRS) caused by CAR-T cells, but its correlation with therapeutic efficacy has not been systematically studied. This study focused on the effects of the TB level on both the safety and efficacy of ssCART-19 as a treatment for r/r B-ALL. Taking the 5% tumor burden as the boundary, the study participants were divided into 2 groups, high and low tumor burden groups. Under this grouping strategy, the impacts of differential r/r B-ALL TBs on the clinical therapeutic efficacy (CR rate and long-term survival) and safety profiles after ssCART-19 cell treatment were analysed. 78 patients were reported in this study. The differential B-ALL TBs significantly affected the complete remission (CR) rates of patients treated with ssCART-19, with rates of 93.94% and 75.56% in the low and high TB groups, respectively (P = 0.0358). The effects of TBs on long-term therapeutic efficacy were further studied based on event-free survival (EFS) and overall survival (OS) profiles; both the OS and EFS of the low TB group were better than those of the high TB group, but the differences were not statistically significant. Importantly, the time points of TB measurement did not significantly affect the OS and EFS profiles regardless of whether the TBs were measured before or after fludarabine-cyclophosphamide (FC) preconditional chemotherapy. On the other hand, the severity of CRS was significantly correlated with the TB level (P = 0.0080), and the incidence of sCRS was significantly related to the TB level (the sCRS incidence increased as the TB level increased, P = 0.0224). Unexpectedly, the ssCART-19 cell expansion peaks were not significantly different (P = 0.2951) between the study groups. Patients with a low r/r B-ALL TB yield more net benefits from CAR-T treatment than those with a high TB in terms of safety and CR rate. These findings are critical and valuable for determining the optimal CAR-T cell treatment window for r/r B-ALL patients and will further the development of comprehensive and reasonable CAR-T cell treatment plans for r/r B-ALL patients with differential TBs.Trial registration: ClinicalTrials.gov identifier, NCT03919240.

The attractiveness of public-private partnership for road projects in India

The objective of this paper was to have a study on the perceptions of stakeholders of Public-Private Partnership (PPP) projects for factors affecting the attractiveness of road projects in India. A questionnaire survey was conducted among major PPP project participants of Indian PPP road projects. Fifteen attractive factors were shortlisted through a literature survey for designing the questionnaire. Collected data was analyzed with factor analysis and descriptive statistical analysis. The findings resulted in three components: effectiveness of the private sector, effective time and cost management, and the public sector’s economic benefit. Eight factors were identified as highly affecting the attractiveness of PPP in Indian road projects. PPP provides ample diversity of net benefits to both the public and private sectors. During the project development stage, both sectors have to formulate decisions based on appropriate assessment criteria. Therefore, the reflection of attractive factors will assist the public-sector to select PPP in the road sector. It also helps to establish the strategy for road projects using PPP.

An Explanatory Study of User Satisfaction

In achieving one of Brunei Vision 2035, which is to be among the top 10 in the world for quality of life, Ministry of Health (MOH) Brunei Darussalam has responded by implementing Brunei Healthcare Information and Management System (Bru-HIMS) that is equivalent to international best practices. Bru-HIMS has been implemented for about eight years since it first launched on 11 September 2012 where the outcome to user experience is unknown. Hence, this chapter investigates user satisfaction on Bru-HIMS specifically at RIPAS hospital and studies improvement towards providing quality healthcare in Brunei. DeLone and McLean Information System framework is applied to evaluate Bru-HIMS user satisfaction based on the six variables: information quality, system quality, service quality, intention to use and usage, perceived net benefits, and user satisfaction. Questionnaire survey was conducted to obtain primary data from Bru-HIMS. The findings demonstrate positive relationships between the six variables, which indicates Bru-HIMS has positively influenced Bru-HIMS users.

Time Reallocation and the Cost and Benefit of School Closures during an Epidemic

School closures are an important public health intervention during epidemics. Yet, the existing estimates of policy costs and benefits overlook the impact of human behavior and labor market conditions. We use an integrated assessment framework to quantify the public health benefits and the economic costs of school closures based on activity patterns derived from the American Time-Use Survey (ATUS) for a pandemic like COVID-19. We develop a policy decision framework based on marginal benefits and costs to estimate the optimal school closure duration. The results suggest that the optimal school closure depends on how people reallocate their time when schools are closed. Widespread social distancing behavior implemented early and for a long duration can delay the epidemic for years, buying time for the development of pharmaceutical interventions and yielding substantial net benefits. Conversely, school closure, with behavior targeted to adjust only to the school closure, is unlikely to provide substantial delay or sufficient net benefits to justify closing schools for pathogen control.

Reforming Energy Subsidy in Kuwait: Maximizing Net Benefits and Equity Complying

The net benefits and public acceptance for a proposed reform to the current subsidization of energy in the State of Kuwait was investigated in this study. The proposed subsidization suggests that the government pays the consumers the subsidization cost in advance and in exchange for raising the subsidized tariffs to full price. The consumption will likely be reduced by a rate equals the over consumption due to the current subsidized tariffs in relative to the income. The net benefits is expected to be maximized and shifted to a pseudo-equilibrium point where both the governments and the consumers will be better off financially. The public acceptance toward the proposed strategy was examined using 274 voluntarily one-to-one interviews for gasoline and 121 for electricity and water. Also, a utilities meters reading program was conducted on 90 houses out of the 121 interviews for utilities. The interviews for gasoline and utilities indicated 57% and 66% of the respondents see no equity in the current subsidization, 55% and 80% admitted to overuse, and 11% and 21% averages of the over consumptions, and 67% and 66% of the respondents were willing to adopt the new strategy. The consumer is expected to save 912 USD/year from gasoline, and 8,198 USD/year from utilities. The estimated net benefits is 5,841 million USD annually with 62% attributed to utilities benefits and 38% to gasoline benefits.

Optimal fertilization dose in castor bean (Ricinus communis L.) using partial budgets analysis

Objective: To determine the economically adequate fertilization dose for a castor bean (Ricinus communis L.) crop that improves the producer's benefits using the partial budgeting technique. Design / methodology / approach: The experiment was established at a site located 500 m from the Centro de Chiapas experimental field, with an altitude of 800 m. Two production factors were studied: nitrogen (40, 60, and 80) and phosphorus (20, 40, and 60) with three levels each. The treatments had nine combinations in a randomized complete block experimental design and four replications. Phenological and morphological variables, seed yield, and variable costs economic components were evaluated as a response. Results: With the average yields the obtained net benefits were determined; an adjustment of the benefits was made, and its dominance was determined. Four experiments were dominated, and five showed favorable profits for the producer. The 80-60-00 formulation had a return rate (RR) of 23 %. Conclusions: The 40-20-00, 40-40-00, 40-60-00, 80-40-00 and 80-60-00 formulations were dominant. The 80-60-00 formulation reported the highest RR, an increase in variable cost of US$9.64, like other doses of lower costs and benefits. For this dose, the net benefits increase was us$ 222.61.

Development and Validation of the Individualized Prognostic Nomograms in Patients With Right- and Left-Sided Colon Cancer

BackgroundThe overall survival (OS) of patients diagnosed with colon cancer (CC) varied greatly, so did the patients with the same tumor stage. We aimed to design a nomogram that is capable of predicting OS in resected left-sided colon cancers (LSCC) and right-sided colon cancers (RSCC), and thus to stratify patients into different risk groups, respectively.MethodsRecords from a retrospective cohort of 577 patients with complete information were used to construct the nomogram. Univariate and multivariate analyses screened risk factors associated with overall survival. The performance of the nomogram was evaluated with concordance index (c-index), calibration plots, and decision curve analyses for discrimination, accuracy, calibration ability, and clinical net benefits, respectively, which was further compared with the American Joint Committee on Cancer (AJCC) 8th tumor-node-metastasis (TNM) classification. Risk stratification based on nomogram scores was performed with recursive partitioning analysis.ResultsThe LSCC nomogram incorporated carbohydrate antigen 12-5 (CA12-5), age and log odds of positive lymph nodes (LODDS), and RSCC nomogram enrolled tumor stroma percentage (TSP), age and LODDS. Compared with the TNM classification, the LSCC and RSCC nomograms both had a statistically higher C-index (0.837, 95% CI: 0.827–0.846 and 0.780, 95% CI 0.773–0.787, respectively) and more clinical net benefits, respectively. Calibration plots revealed no deviations from reference lines. All results were reproducible in the validation cohort.ConclusionsAn original predictive nomogram was constructed and validated for OS in patients with CC after surgery, which had facilitated physicians to appraise the individual survival of postoperative patients accurately and to identify high-risk patients who were in need of more aggressive treatment and follow-up strategies.

Rainwater Harvesting and Rural Livelihoods in Nepal

Springs are drying and rainfall patterns are changing in the Himalayas, resulting in water scarcityfor agriculture. We examine the adoption of rainwater harvesting, a technology that has been recently re-designed and re-introduced to farmers in Nepal, as a climate change adaptation strategy in mountain farming. Using farm household surveys, we examine the impact of the adoption of rainwater harvestingon farm income and profitability. The adoption of the technology is mostly driven by external support such as farmers training that more than tripled household agricultural and livestock income. With incremental annual benefits of US$700 on average per adopter, this technology is economically viable from a household perspective. Adopters benefit from an increased supply of irrigation water during the dry season, which allows them to diversify their crops from subsistence cereal production to commercial high-value vegetables. Our analysis suggests that if 10% of households in an average rainfed district receive farming-related training, the net benefits in the district would be approximately US$1.3 million per year from the adoption of rain water harvesting technology. Given climatic and weather-related uncertainties faced by rainfed agriculture in the hills of Nepal, this technology is potentially a very useful climate change adaptation strategy for community resilience in the hills of Nepal.

Economic disparity among generations under the Paris Agreement

The costs and benefits of climate change mitigation are known to be distributed unevenly across time and space, while their intergenerational distribution across nations has not been evaluated. Here, we analyze the lifetime costs and benefits of climate change mitigation by age cohorts across countries under the Paris Agreement. Our results show that the age cohorts born prior to 1960 generally experience a net reduction in lifetime gross domestic product per capita. Age cohorts born after 1990 will gain net benefits from climate change mitigation in most lower income countries. However, no age cohorts enjoy net benefits regardless of the birth year in many higher income countries. Furthermore, the cost-benefit disparity among old and young age cohorts is expected to widen over time. Particularly, lower income countries are expected to have much larger cost-benefit disparity between the young and the old. Our findings highlight the challenges in building consensus for equitable climate policy among nations and generations.