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The world is increasingly getting urbanized and globalized, and the increase in natural resource exploration could have a far-reaching impact on environmental quality. Since most Latin American and Caribbean countries (LACCs) have proximity to the Amazon, they, therefore, rely heavily on agriculture and mining which develop via deforestation which could exacerbate the already increasing carbon dioxide emissions (CO 2 emissions). Therefore, to the best of our knowledge, this study becomes the first to investigate the link between natural resources, globalization, urbanization, and environmental degradation in LACCs countries from 1990 to 2017 with advanced panel data econometric techniques. The unit root tests affirm all the variables to be stationary at first difference, and the Westerlund (Oxf Bull Econ Stat 69(6):709–748, 2007 ) cointegration test confirms the long-run relationship among the variables. The augmented mean group (AMG) and the common correlated effects mean group (CCEMG) results affirm that the aforementioned variables add to CO 2 emissions, while human capital mitigates it. Further findings reveal that human capital performs a moderating role in promoting urbanization sustainability. The country-specific results confirm that economic growth adds to emissions in all the countries, except in the Dominican Republic. A feedback causality exists between economic growth, globalization, urbanization, and CO 2 emissions. This study argues for the development of human capital, a gradual transition to sustainable growth-driven and knowledge-based industries, and the introduction of sustainability practices in the natural resource sector to mitigate CO 2 emissions in LACCs.

Key Points The detection of noxious stimuli by nociceptors is mediated by high-threshold transducers expressed on their peripheral terminal membranes. These transducers are receptor/ion channels that convert thermal, mechanical and chemical stimuli into ion fluxes that excite the neuron to produce a sensory inflow. Transient receptor potential (TRP) channels are the most prominent family of nociceptive ion-channel transducer proteins and encode thermal and chemical stimuli. Among the TRP channels expressed by nociceptors, TRPV1 and TRPA1 have been the most extensively investigated, and represent validated targets for the development of novel analgesics. In addition to detecting noxious stimuli, the density, threshold and kinetics of TRPV1 and TRPA1 are modulated by inflammatory mediators, and in this way sensitize nociceptors to increase pain sensitivity after tissue damage or on exposure to inflammation. TRPV1 and TRPA1 are also expressed on the central terminals of sensory neurons where they seem to act as synaptic modulators. Antagonists acting at these two channels are promising candidates as analgesics by virtue of blocking the activation of the channels in response to noxious stimuli or inflammation. TRP nociceptive transducer proteins may have adaptive actions beyond simply detecting noxious stimuli, including body temperature control, synaptic plasticity, and respiratory and cardiovascular function, which may produce adverse effects when blocked. TRP channel agonists can also produce analgesia by either desensitizing the receptors or, at high doses, ablating them. TRP channels can be used as a drug delivery system to target small cationic drugs selectively into nociceptors. Overall, targeting nociceptive TRP channels, where the pain-pathway begins, represents a promising opportunity for the development of novel analgesics. Transient receptor potential (TRP) channels are the most prominent family of nociceptive ion-channel transducer proteins. This Review highlights evidence supporting particular TRP channels as targets for analgesics, indicates the likely efficacy profiles of TRP-channel-acting compounds and looks at recent clinical trials with TRP-channel-acting drugs. Pain results from the complex processing of neural signals at different levels of the central nervous system, with each signal potentially offering multiple opportunities for pharmacological intervention. A logical strategy for developing novel analgesics is to target the beginning of the pain pathway, and aim potential treatments directly at the nociceptors — the high-threshold primary sensory neurons that detect noxious stimuli. The largest group of receptors that function as noxious stimuli detectors in nociceptors is the transient receptor potential (TRP) channel family. This Review highlights evidence supporting particular TRP channels as targets for analgesics, indicates the likely efficacy profiles of TRP-channel-acting drugs, and discusses the development pathways needed to test candidates as analgesics in humans.

The purpose of this study was to examine the nexus amid economic growth, energy consumption and carbon emissions in G20 countries for the period 1992 to 2014. In order to obtain valid and reliable outcomes, more robust econometric techniques were employed. From the results, the studied panel was heterogeneous and cross-sectionally dependent. Also, the series of observed variables were first-differenced stationary and co-integrated. The key findings from the CCEMG and the AMG regression estimators adopted showed that economic growth and energy consumption promoted the emission of carbon in the countries. In addition, urbanization and foreign direct investments as control variables escalated the rate of the countries’ CO2 emissions. From the discoveries of the Dumitrescu and Hurlin panel causality test, a feedback causality between economic growth and CO2 emissions; energy consumption and CO2 emissions; and between urbanization and CO2 emissions were correspondingly unveiled. Howerver, a one-way caual link was evidenced from foreign direct investments to CO2 emissions. This exploration is vital because it will propel the countries to formulate policies that could help them to minimize their dependence on environmentally unfriendly energy sources, while promoting the usage of clean energies like solar, wind, biogas, biomass and hydropower among others. The study is also pertinent because it will aid the countries to plan, organize and implement environmental policies in compliance to their macroeconomic objectives. When this is accomplished, energy conservation policies implemented to minimize the emanation of CO2 will improve the countries’ economic growth.

High levels of CO 2 emissions are extensively cited as one of the main global concerns nowadays. Therefore, researchers have been investigating the factors that affect CO 2 emissions. In the prior literature, several social, economic, and political drivers of CO 2 emissions have been investigated; however, there is a dearth of the literature on the impact of geopolitical risks (GPR) on CO 2 emissions. Hence, the objective of this study is to explore the impact of GPR on CO 2 emissions in the case of the BRICS countries while controlling the effects of population, GDP, non-renewable energy, and renewable energy consumption. The study uses the recently developed GPR index, proposed by Caldara and Iacoviello ( 2018 ), and the AMG (augmented mean group) estimator method. The findings document that GPR escalates CO 2 emissions. That is, a 1% increase in GPR escalates CO 2 emissions by 13%. Moreover, it also reports that renewable energy consumption impedes CO 2 emissions. In contrast, GDP, population, and non-renewable energy consumption surge CO 2 emissions. The study also proposes a few policy implications based on the findings: (1) policymakers and government officials should try to limit GPR through peace treaties, agreements, and negotiations; (2) share of renewable energy in total energy consumption should be increased in order to plunge CO 2 emissions.

Increasing healthcare expenses and the ongoing deterioration of the environment have renewed the debate on whether the transition to renewable energy can help reduce the financial burdens of healthcare spending in developing economies. Growing global pressures about worsening air quality with the wider effects of changing the climate on health, especially in more densely populated nations, have underlined the need to investigate long-run policy that can tackle both energy constraints and health issues. This paper examines the long-run associations between health spending and renewable energy use in Pakistan and Nigeria between 2000 and 2024, including environmental quality (PM2.5), economic growth, mortality rate, population and density of physicians. The analysis uses second-generation panel methods, such as cross-sectional dependence tests, unit root tests, Westerlund cointegration, and Augmented Mean Group (AMG) estimator. Further cointegration methods (Kao and Fisher), long-run estimators (FMOLS and DOLS) are used in order to obtain robustness, as well as panel and country-specific Granger tests of causality. The findings validate the existence of an equilibrium long-run relationship between the variables. The consumption of renewable energy is observed to be negatively associated with the spending on health which implies that a shift towards cleaner energy sources is associated with a decrease in healthcare burden in the long-run. On the contrary, environmental degradation in terms of the PM2.5 emissions exhibits a positive relationship with the health expenditure, indicating the elevated health spending linked to pollution exposure. while physician density demonstrates a strong positive relationship, reflecting increased healthcare utilization. The stability of these long run results is ensured by robustness tests. From policy perspective, the results indicate that the increased use of renewable energy could help health spending management in the developing economies in the long run. The concept of clean energy policies can be considered an essential tool of sustainable funding of healthcare and long-term progress in the populous developing economies. However, future studies ought to use larger panel data, deal with endogeneity by employing more effective identification methods, and examine the possible transmission mechanisms between energy, environment, and health outcomes.

In the modern era of globalization, the rapid increase in information and telecommunication technologies (ICTs) contributes in various sectors of an economy; however, the environmental consequences of ICTs cannot be ignored. Therefore, the study investigates the nexus between ICTs, economic growth, financial development, and environmental quality in emerging economies. The novel feature of the study is that the interaction term of ICT is introduced with economic growth and financial development. The empirical findings of the study are based on panel mean group (MG) and augmented mean group (AMG) estimation methods from 1990 to 2015. The following empirical results are established: first the ICTs significantly affect CO 2 emissions. Second, the moderating effect of ICT and financial development stimulate the level of CO 2 emissions. Third, economic growth contributes CO 2 emission; however, the interaction between ICT and GDP mitigates the level of pollution. Policy thresholds with the R&D in ICT sector are required to mitigate the level of CO 2 emission. Introduction of green ICTs projects in the financial sector is a better choice to improve the energy efficiency.

SummaryBackground This open-label, first-in-human, phase 1 study evaluated AMG 232, an oral selective MDM2 inhibitor in patients with TP53 wild-type (P53WT), advanced solid tumors or multiple myeloma (MM). Methods In the dose escalation (n = 39), patients with P53WT refractory solid tumors enrolled to receive once-daily AMG 232 (15, 30, 60, 120, 240, 480, and 960 mg) for seven days every 3 weeks (Q3W). In the dose expansion (n = 68), patients with MDM2-amplified (well-differentiated and de-differentiated liposarcomas [WDLPS and DDLPS], glioblastoma multiforme [GBM], or other solid tumors [OST]), MDM2-overexpressing ER+ breast cancer (BC), or MM received AMG 232 at the maximum tolerated dose (MTD). Safety, pharmacokinetics, pharmacodynamics, and efficacy were assessed. Results AMG 232 had acceptable safety up to up to 240 mg. Three patients had dose-limiting toxicities of thrombocytopenia (n = 2) and neutropenia (n = 1). Due to these and other delayed cytopenias, AMG 232 240 mg Q3W was determined as the highest tolerable dose assessed in the dose expansion. Adverse events were typically mild/moderate and included diarrhea, nausea, vomiting, fatigue, decreased appetite, and anemia. AMG 232 plasma concentrations increased dose proportionally. Increases in serum macrophage inhibitor cytokine-1 from baseline were generally dose dependent, indicating p53 pathway activation. Per local review, there were no responses. Stable disease (durability in months) was observed in patients with WDLPS (3.9), OST (3.3), DDLPS (2.0), GBM (1.8), and BC (1.4–2.0). Conclusions In patients with P53WT advanced solid tumors or MM, AMG 232 showed acceptable safety and dose-proportional pharmacokinetics, and stable disease was observed.

This study investigates the impact of carbon emissions, real oil prices, income inequality, economic growth, and trade openness on renewable energy consumption (REC) in twenty-three (23) OECD economies. The study employs the Westerlund panel cointegration technique to verify the existence of long-run equilibrium and the Augmented Mean Group (AMG) estimator to assess the long-run relationship between the variables, which allows for slope heterogeneity and cross-sectional dependency. Moreover, the panel causality test of Dumitrescu and Hurlin (DH) is utilized to gauge the causal relationship between the variables. The findings of our study reveal that REC is positively related to economic growth, real oil prices, income inequality, and trade openness, but negatively related to CO2 emissions in OECD countries. In addition, there is one-way causality from GDP per capita to renewable energy consumption and a bidirectional causality between income inequality and REC. Furthermore, the results indicate that OECD policymakers and governments should regard foreign trade as a \"clean energy fostering mechanism\" while developing energy demand policies that are environmentally friendly.This study investigates the impact of carbon emissions, real oil prices, income inequality, economic growth, and trade openness on renewable energy consumption (REC) in twenty-three (23) OECD economies. The study employs the Westerlund panel cointegration technique to verify the existence of long-run equilibrium and the Augmented Mean Group (AMG) estimator to assess the long-run relationship between the variables, which allows for slope heterogeneity and cross-sectional dependency. Moreover, the panel causality test of Dumitrescu and Hurlin (DH) is utilized to gauge the causal relationship between the variables. The findings of our study reveal that REC is positively related to economic growth, real oil prices, income inequality, and trade openness, but negatively related to CO2 emissions in OECD countries. In addition, there is one-way causality from GDP per capita to renewable energy consumption and a bidirectional causality between income inequality and REC. Furthermore, the results indicate that OECD policymakers and governments should regard foreign trade as a \"clean energy fostering mechanism\" while developing energy demand policies that are environmentally friendly.

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with a poor prognosis. Initial responses to standard-of-care chemo-immunotherapy are, unfortunately, followed by rapid disease recurrence in most patients. Current treatment options are limited, with no therapies specifically approved as third-line or beyond. Delta-like ligand 3 (DLL3), a Notch inhibitory ligand, is an attractive therapeutic target because it is overexpressed on the surface of SCLC cells with minimal to no expression on normal cells. Several DLL3-targeted therapies are being developed for the treatment of SCLC and other neuroendocrine carcinomas, including antibody-drug conjugates (ADCs), T-cell engager (TCE) molecules, and chimeric antigen receptor (CAR) therapies. First, we discuss the clinical experience with rovalpituzumab tesirine (Rova-T), a DLL3-targeting ADC, the development of which was halted due to a lack of efficacy in phase 3 studies, with a view to understanding the lessons that can be garnered for the rapidly evolving therapeutic landscape in SCLC. We then review preclinical and clinical data for several DLL3-targeting agents that are currently in development, including the TCE molecules—tarlatamab (formerly known as AMG 757), BI 764532, and HPN328—and the CAR T-cell therapy AMG 119. We conclude with a discussion of the future challenges and opportunities for DLL3-targeting therapies, including the utility of DLL3 as a biomarker for patient selection and disease progression, and the potential of rational combinatorial approaches that can enhance efficacy.