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The imperative to enhance corporate environmental performance is not only pivotal for a company's growth but also crucial for fulfilling societal responsibilities and protecting global environmental interests. Recognizing the inadequacies of standalone environmental policies, our study delves into the synergistic effects of incentive-based and regulatory approaches on the environmental performance of listed firms in China. We meticulously examine the interplay between environmental punishment and subsidies over the period of 2015-2019. Our analysis reveals that a strategic combination of punishment and subsidies can substantially improve firms' environmental performance. This effect intensifies with the increasing amounts of fines and subsidies. Additionally, we explore the dynamic effects of policy implementation. Our results indicate that subsidies implemented either a year before or after the imposition of punishment might diminish the effectiveness of standalone environmental penalty policies. Furthermore, our findings suggest that diverse regulatory policies enhance firm environmental performance by promoting investments in environmental protection and fostering green innovation. This discovery highlights the need for a nuanced understanding of policy mixes and their implications for corporate environmental strategies.

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BACKGROUND: Current standard of care for advanced biliary tract cancer (BTC) is gemcitabine, cisplatin plus anti-PD1/PD-L1, but response rates are modest. The purpose of this study was to explore the efficacy and safety of durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4), with and without an interventional radiology (IR) procedure in advanced BTC. METHODS: Eligible patients with advanced BTC who had received or refused at least one prior line of systemic therapy were treated with tremelimumab and durvalumab for four combined doses followed by monthly durvalumab alone with and without an IR procedure until the progression of disease or unacceptable toxicity. Objective response was assessed through CT or MRI by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) every 8 weeks. Adverse events (AEs) were recorded and managed. The primary endpoint was 6-month progression-free survival (PFS). RESULTS: Twenty-three patients with advanced BTC were enrolled; 17 patients were assigned to treatment with durvalumab and tremelimumab (Durva/Treme); and 6 patients were treated with the combination of durvalumab, tremelimumab plus IR procedure (Durva/Treme + IR). The best clinical responses in the Durva/Treme arm were partial response (n = 1), stable disease (n = 5), progressive disease (n = 5), and in the Durva/Treme + IR arm: partial response (n = 0), stable disease (n = 3), progressive disease (n = 3). The median PFS was 2.2 months (95% CI: 1.3-3.1 months) in the Durva/Treme arm and 2.9 months (95% CI: 1.9-4.7 months) in the Durva/Treme + IR arm (p = 0.27). The median OS was 5.1 months (95% CI: 2.5-6.9 months) in the Durva/Treme arm and 5.8 months (95% CI: 2.9-40.1 months) in the Durva/Treme + IR arm (p = 0.31). The majority of AEs were grades 1-2. CONCLUSION: Durva/Treme and Durva/Treme + IR showed similar efficacy. With a manageable safety profile. Larger studies are needed to fully characterize the efficacy of Durva/Treme ± IR in advanced BTC.

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BACKGROUND: Microsatellite stable colorectal liver metastases (MSS CLM) maintain an immunosuppressive tumor microenvironment (TME). Historically, immune-based approaches have been ineffective. VB-111 (ofranergene obadenovec) is a genetically-modified adenoviral vector targeting the TME; its unique dual mechanism induces an immune response and disrupts neovascularization. Checkpoint inhibition may synergize the immune response induced by viral-mediated anti-angiogenic gene therapy. We aimed to examine the safety and antitumor activity of VB-111 and nivolumab in patients with refractory MSS CLM and to characterize immunological treatment-response. METHODS: This was a phase II study of adult patients with histologically-confirmed MSS CLM who progressed on prior therapy. A priming dose of VB-111 1×1013 viral particles was given intravenously 2 weeks prior to starting biweekly nivolumab 240 mg and continued every 6 weeks. The combination continued until disease progression or unacceptable toxicity. The primary objectives were overall response rate and safety/tolerability. Secondary objectives included median overall survival and progression-free survival. Correlative studies were performed on paired tumor biopsies and blood. RESULTS: Between August 2020 and December 2021, 14 patients were enrolled with median age 50.5 years (40-75), and 14% were women. Median follow-up was 5.5 months. Of the 10 evaluable patients, the combination of VB-111 and nivolumab failed to demonstrate radiographic responses; at best, 2 patients had stable disease. Median overall survival was 5.5 months (95% CI: 2.3 to 10.8), and median progression-free survival was 1.8 months (95% CI: 1.4 to 1.9). The most common grade 3-4 treatment-related adverse events were fever/chills, influenza-like symptoms, and lymphopenia. No treatment-related deaths were reported. Qualitative analysis of immunohistochemical staining of paired tumor biopsies did not demonstrate significant immune infiltration after treatment, except for one patient who had exceptional survival (26.0 months). Immune analysis of peripheral blood mononuclear cells showed an increase of PD-1highKi67highCD8+ T cells and HLA-DRhigh T cells after VB-111 priming dose. Plasma cytokines interleukin-10 and tumor necrosis factor-α increased after treatment with both drugs. CONCLUSION: In patients with MSS CLM, VB-111 and nivolumab did not improve overall response rate or survival but were tolerated with minimal toxicities. While challenging to distinguish between antiviral or antitumor, correlative studies demonstrated an immune response with activation and proliferation of CD8+ T cells systemically that was poorly sustained. TRIAL REGISTRATION NUMBER: NCT04166383.

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China is facing challenges to tackle the threat of climate change while reducing social inequality. Poverty eradication requires improvement in the living conditions of low-income households, which leads in turn to higher carbon footprints and may undermine the efforts of climate change mitigation. Previous studies have assessed the climate impacts of poverty eradication, but few have quantified how the additional carbon emissions of poverty eradication are shared at the subnational level in China and the impact on China's climate targets. We investigated the recent trend of carbon footprint inequality in China's provinces and estimated the climate burden of different poverty reduction schemes, measured by increased carbon emissions. The results indicate that poverty eradication will not impede the achievement of national climate targets, with an average annual household carbon footprint increase of 0.1%-1.2%. However, the carbon emissions growth in less developed provinces can be 4.0%, five times that in wealthy regions. Less developed regions suffer a greater climate burden because of poverty eradication, which may offset carbon reduction efforts. Therefore, interregional collaboration is needed to coordinate inequality reduction with investments in low-carbon trajectories in all provinces.

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Limiting climate change to 1.5°C and achieving net-zero emissions would entail substantial carbon dioxide removal (CDR) from the atmosphere by the mid-century, but how much CDR is needed at country level over time is unclear. The purpose of this paper is to provide a detailed description of when and how much CDR is required at country level in order to achieve 1.5°C and how much CDR countries can carry out domestically. We allocate global CDR pathways among 170 countries according to 6 equity principles and assess these allocations with respect to countries' biophysical and geophysical capacity to deploy CDR. Allocating global CDR to countries based on these principles suggests that CDR will, on average, represent ∼4% of nations' total emissions in 2030, rising to ∼17% in 2040. Moreover, equitable allocations of CDR, in many cases, exceed implied land and carbon storage capacities. We estimate ∼15% of countries (25) would have insufficient land to contribute an equitable share of global CDR, and ∼40% of countries (71) would have insufficient geological storage capacity. Unless more diverse CDR technologies are developed, the mismatch between CDR liabilities and land-based CDR capacities will lead to global demand for six GtCO2 carbon credits from 2020 to 2050. This demonstrates an imperative demand for international carbon trading of CDR.

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Globally, primary liver cancer is the third leading cause of cancer-related deaths, with approximately 830 000 deaths worldwide in 2020, accounting for 8.3% of total deaths from all cancer types (1). This disease disproportionately affects those in countries with low or medium Human Development Index scores in Eastern Asia, South-Eastern Asia, and Northern and Western Africa (2). Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, often develops in the background of chronic liver disease, caused by hepatitis B or C virus, non-alcoholic steatohepatitis (NASH), or other diseases that cause cirrhosis. Prognosis can vary dramatically based on number, size, and location of tumors. Hepatic synthetic dysfunction and performance status (PS) also impact survival. The Barcelona Clinic Liver Cancer (BCLC) staging system best accounts for these variations, providing a reliable prognostic stratification. Therapeutic considerations of this complex disease necessitate a multidisciplinary approach and can range from curative-intent surgical resection, liver transplantation or image-guided ablation to more complex liver-directed therapies like transarterial chemoembolization (TACE) and systemic therapy. Recent advances in the understanding of the tumor biology and microenvironment have brought new advances and approvals for systemic therapeutic agents, often utilizing immunotherapy or VEGF-targeted agents to modulate the immune response. This review will discuss the current landscape in the treatments available for early, intermediate, and advanced stage HCC.

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CO2 emissions are unevenly distributed both globally and regionally within nation-states. Given China's entrance into the new stage of economic development, an updated study on the largest CO2 emitter's domestic emission distribution is needed for effective and coordinated global CO2 mitigation planning. We discovered that domestic CO2 emissions in China are increasingly polarized for the 2007-2017 period. Specifically, the domestically exported CO2 emissions from the less developed and more polluting northwest region to the rest of China has drastically increased from 165 Mt in 2007 to 230 Mt in 2017. We attribute the polarizing trend to the simultaneous industrial upgrading of all regions and the persistent disparity in the development and emission decoupling of China's regions. We also noted that CO2 emissions exported from China to the rest of the world has decreased by 41% from 2007 to 2017, with other developing countries filling up the vacancy. As this trend is set to intensify, we intend to send an alarm message to policy makers to devise and initiate actions and avoid the continuation of pollution migration.

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This commentary reviews top advances in hepatobiliary cancer research in 2021-2022, focusing on leveraging immunotherapeutics in combination with other therapies earlier in the disease course and targeted to patient's individualized biomarkers that may predict response or resistance to checkpoint inhibitors.

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Responsive feeding, where parents are guided by children's hunger and satiation cues and provide appropriate structure and support for eating, is believed to promote healthier weight status. However, few studies have assessed prospective associations between observed parental feeding and toddler growth. We characterized toddler growth from 18 to 36 months and, in a subset of families, examined whether observed maternal responsiveness to toddler satiation cues and encouraging prompts to eat at 18 and 24 months were associated with toddler body mass index z-score (BMIz) from 18 to 36 months. Participants included 163 toddlers and their mothers with overweight/obesity who had participated in a lifestyle intervention during pregnancy. Anthropometrics were measured at 18, 24, and 36 months. In a subsample, mealtime interactions were recorded in families' homes at 18 (n = 77) and 24 (n = 75) months. On average, toddler BMIz remained stable from 18 to 36 months with 31.3% (n = 51) categorized with a healthy weight, 56.4% (n = 92) with at risk for overweight and 12.3% (n = 20) with overweight. Fewer maternal prompts to eat at 18 months was associated with both higher probability of having at risk for overweight/overweight (p < .05), and higher child 36-month BMIz (p = .002). Higher child weight status at 12 months was also associated with both higher probability of having at risk for overweight/overweight (p < .05), and higher child 36-month BMIz (p < .001). Neither 24-month maternal prompts nor 18 or 24 month responsiveness to satiation cues were associated with toddler BMIz. In this diverse sample, weight status was relatively stable from 18 to 36 months. Maternal prompts to eat measured earlier in toddlerhood and prior child weight status were associated with toddler BMIz.

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Globally most governments implemented a 'Working from Home' (home office) strategy to contain the spread of the coronavirus in 2020 in order to ensure public safety and minimize the transmission of the virus. Unsurprisingly studies have found that COVID-19 has had a detrimental impact on urban transportation systems; however, the number of shared bicycle riders is progressively growing compared to other modes of public transit. The aim of this study is to investigate the influence of COVID-19 on the usage of shared bicycle systems in order to identify passenger travel patterns and habits. In addition, bicycle rentals are becoming more popular in some locations. This demonstrates that bike sharing as a transport option has a high level of social adaptability and is progressively being adopted by the general population in a fashion that promotes the resilience of transport systems.

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BACKGROUND: The health impacts of ambient air pollution impose large costs on society. Although all people are exposed to air pollution, the older population (ie, those aged ≥60 years) tends to be disproportionally affected. As a result, there is growing concern about the health impacts of air pollution as many countries undergo rapid population ageing. We investigated the spatial and temporal variation in the economic cost of deaths attributable to ambient air pollution and its interaction with population ageing from 2000 to 2016 at global and regional levels. METHODS: In this global analysis, we developed an age-adjusted measure of the value of a statistical life-year (VSLY) to estimate the economic cost of deaths attributable to ambient PM2·5 pollution using Global Burden of Diseases, Injuries, and Risk Factors Study 2017 data and country-level socioeconomic information. First, we estimated the global age-specific and cause-specific mortality and years of life lost (YLLs) attributable to PM2·5 pollution using the global exposure mortality model and global estimates of exposure at 0·1°â€ˆ× 0·1° (about 11 km × 11 km at the equator) resolution. Second, for each year between 2000 and 2016, we translated the YLLs within each age group into a health-related cost using a country-specific, age-adjusted measure of VSLY. Third, we decomposed the major driving factors that contributed to the temporal change in health costs related to PM2·5. Finally, we did a sensitivity test to analyse the variability of the estimated health costs to four alternative valuation measures. We identified the uncertainty intervals (UIs) from 1000 draws of the parameters and concentration-response functions by age, cause, country, and year. All economic values are reported in 2011 purchasing power parity-adjusted US dollars. All simulations were done with R, version 3.6.0. FINDINGS: Globally, in 2016, PM2·5 was estimated to have caused 8·42 million (95% UI 6·50-10·52) attributable deaths, which was associated with 163·68 million (116·03-219·44) YLLs. In 2016, the global economic cost of deaths attributable to ambient PM2·5 pollution for the older population was US$2·40 trillion (1·89-2·93) accounting for 59% (59-60) of the cost for the total population ($4·09 trillion [3·19-5·05]). The economic cost per capita for the older population was $2739 (2160-3345) in 2016, which was 10 times that of the younger population (ie, those aged <60 years). By assessing the factors that contributed to economic costs, we found that increases in these factors changed the total economic cost by 77% for gross domestic product (GDP) per capita, 21% for population ageing, 16% for population growth, -41% for age-specific mortality, and -0·4% for PM2·5 exposure. INTERPRETATION: The economic cost of ambient PM2·5 borne by the older population almost doubled between 2000 and 2016, driven primarily by GDP growth, population ageing, and population growth. Compared with younger people, air pollution leads to disproportionately higher health costs among older people, even after accounting for their relatively shorter life expectancy and increased disability. As the world's population is ageing, the disproportionate health cost attributable to ambient PM2·5 pollution potentially widens the health inequities for older people. Countries with severe air pollution and rapid ageing rates need to take immediate actions to improve air quality. In addition, strategies aimed at enhancing health-care services, especially targeting the older population, could be beneficial for reducing the health costs of ambient air pollution. FUNDING: National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Qiushi Foundation.

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Countries have sought to stop the spread of coronavirus disease 2019 (COVID-19) by severely restricting travel and in-person commercial activities. Here, we analyse the supply-chain effects of a set of idealized lockdown scenarios, using the latest global trade modelling framework. We find that supply-chain losses that are related to initial COVID-19 lockdowns are largely dependent on the number of countries imposing restrictions and that losses are more sensitive to the duration of a lockdown than its strictness. However, a longer containment that can eradicate the disease imposes a smaller loss than shorter ones. Earlier, stricter and shorter lockdowns can minimize overall losses. A 'go-slow' approach to lifting restrictions may reduce overall damages if it avoids the need for further lockdowns. Regardless of the strategy, the complexity of global supply chains will magnify losses beyond the direct effects of COVID-19. Thus, pandemic control is a public good that requires collective efforts and support to lower-capacity countries.

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Reducing fossil fuel consumption is a top priority option for climate change mitigation, which requires collaborations of partners along the supply chain, such as energy suppliers, energy consumers and final consumers of goods and services. A comprehensive analysis of fossil fuel consumption is useful for policymakers to reduce demand but still absent. This study explores the national contribution to global energy consumption from different perspectives in the global supply chain and is designed to complement current energy reduction policies. For the developed countries, energy consumptions are stable from 2000 to 2014, while that of emerging countries almost doubled (e.g., China and India). Most of the developing countries are producers whose production-based and final production-based energy consumptions are higher than their consumption-based ones, except India after the global financial crisis. In contrast, the developed countries are consumers, whose consumption-based energy consumptions are higher. At the sectoral level, the service sector is the largest contributor to consumption- and income-based energy consumption. The analysis in this study can create opportunities for all the parties alongside the supply chain in reducing fossil fuel consumption.

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Lanthanum hexaboride (LaB6) has become a material of intense interest in recent years due to its low work function, thermal stability and intriguing optical properties. LaB6 is also a semiconductor plasmonic material with the ability to support strong plasmon modes. Some of these modes uniquely stretch into the infrared, allowing the material to absorb around 1000 nm, which is of great interest to the window industry. It is well known that the plasmon of LaB6 can be tuned by controlling particle size and shape. In this work, we explore the options available to further tune the optical properties by describing how metal vacancies and Eu doping concentrations are additional knobs for tuning the absorbance from the near-IR to far-IR in La1-xEuxB6 (x = 0, 0.2, 0.5, 0.8, and 1.0). We also report that there is a direct correlation between Eu concentration and metal vacancies within the Eu1-xLaxB6.

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Snacking makes significant contributions to children's dietary intake but is poorly understood from a parenting perspective. This research was designed to develop and evaluate the psychometrics of a theoretically grounded, empirically-informed measure of snack parenting. The Parenting around SNAcking Questionnaire (P-SNAQ) was developed using a conceptual model derived from current theory and mixed-methods research to include 20 hypothesized snack parenting practices along 4 parenting dimensions (autonomy support, structure, coercive control and permissiveness). Expert panel evaluation and cognitive interviews were used to refine items and construct definitions. The initial instrument of 105 items was administered to an ethnically diverse, low-income sample of 305 parents (92% mothers) of children aged 1-6 y participating in three existing cohort studies. The sample was randomly split into two equal samples. Exploratory factor analysis was conducted with the first sample to identify snack parenting practices within each parenting dimension, followed by confirmatory factor analysis with the second sample to test the hypothesized factor structure. Internal consistency of sub-scales and associations with existing measures of food parenting practices and styles and child weight status were evaluated. The final P-SNAQ scale included 51 items reflecting 14 snack parenting practices across four parenting dimensions. The factor structure of the P-SNAQ was consistent with prior theoretical frameworks. Internal consistency coefficients were good to very good for 12 out of 14 scales and subscale scores were moderately correlated with previously validated measures. In conclusion, initial evidence suggests that P-SNAQ is a psychometrically sound measure for evaluating a wide range of snack parenting practices in young children.

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OBJECTIVES: To determine the associations between diet quality, body mass index (BMI), and health-related quality of life (HRQOL) as assessed by the health and activity limitation index (HALex) in older adults. DESIGN: Multivariate linear regression models were used to analyze associations between Dietary Screening Tool (DST) scores, BMI and HALex score, after controlling for gender, age, education, living situation, smoking, disease burden and self-vs. proxy reporting. SETTING: Geisinger Rural Aging Study, Pennsylvania. PARTICIPANTS: 5,993 GRAS participants were mailed HRQOL and DST questionnaires with 4,009 (1,722 male, 2,287 female; mean age 81.5 ± 4.4) providing complete data. RESULTS: HALex scores were significantly lower for participants with dietary intakes categorized as unhealthy (<60) (0.70, 95% CI 0.69, 0.72, p<0.05) or borderline (60-75) (0.71, 95% CI 0.70, 0.73, p<0.05) compared to those scoring in the healthy range (>75) (0.75, 95% CI 0.73, 0.77) based on DST scores. HALex scores were significantly lower for underweight (0.67, 95% CI 0.63, 0.72, p<0.05), obese class II (0.68, 95% CI 0.66, 0.71, p<0.05) and class III participants (0.62 95% CI 0.57, 0.67, p<0.05) compared to those with BMI 18.5-24.9. CONCLUSIONS: Poor diet quality, as assessed by the DST, is associated with lower HRQOL in adults ≥ 74 years of age.

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BACKGROUND: The prevalence of obesity-related adverse health outcomes is increasing among older adults. Because it is thought that nutrition plays an important role in successful aging, there has been considerable interest in the association between dietary patterns of older adults and obesity-related health outcomes. OBJECTIVE: This study examined the association between dietary patterns and mortality and prevalence of obesity-related health outcomes, namely cardiovascular disease (CVD), type 2 diabetes mellitus, hypertension, and metabolic syndrome (MetSyn), over a 5-year follow-up period in adults aged 75 years or greater. DESIGN: A longitudinal observational study with cross-sectional dietary assessment. SETTING: Rural Central Pennsylvania. PARTICIPANTS: Community-dwelling older adults (N = 449; 76.5 years old; 57% female). MEASUREMENTS: Multiple, unannounced, 24-hour dietary recalls were used to collect dietary intake. Cluster analysis was used to derive dietary patterns. Prevalence of CVD, diabetes mellitus, hypertension, and MetSyn was extracted from outpatient electronic medical records. Logistic regression was used to examine the associations between dietary patterns and health outcomes and mortality. RESULTS: 'Sweets and Dairy', 'Health-Conscious' and 'Western' dietary patterns were identified. Compared to the 'Health-Conscious' pattern, those in the 'Sweets and Dairy' pattern had increased odds of hypertension over the follow-up period; adjusted odds ratio (95% CI) was 2.18 (1.11-4.30). No significant associations were found for CVD, diabetes mellitus, MetSyn or mortality with dietary patterns. CONCLUSIONS: These findings support the potential value of healthy dietary patterns in the management of hypertension in older adults. We did not observe any other strong associations between dietary patterns and health outcomes or mortality in persons ≥ 75 years of age; thus failing to support the use of overly restrictive diet prescriptions for older persons, especially where food intake may be inadequate.

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