Novel therapeutics for patients with well-differentiated gastroenteropancreatic neuroendocrine tumors

Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) represent the most common subtype of NETs. The incidence of all NETs, and specifically GEP NETs, has risen exponentially over the last three decades. Only within the past several years have these tumors been appropriately classified, allowing for meaningful drug development. Broadly, some of the most exciting drug classes being developed for patients with well-differentiated GEP NETs include newer types of peptide receptor radionuclide therapy (PRRT) or combinations which increase the potency of lutetium-177 (177Lu)-Dotatate, novel multi-target receptor tyrosine kinase inhibitors (RTKIs) and immunotherapy modalities, beyond checkpoint inhibitors, which seek to unleash the immune system against NETs. Specifically looking at newer types of PRRT, somatostatin receptor antagonists and alpha-emitter radionuclides each have demonstrated the ability to elicit greater DNA damage than 177Lu-Dotatate in preclinical models. Early clinical experiences with each of these agents suggest they may be more cytotoxic than 177Lu-Dotatate. Other approaches seeking to build upon the DNA damage created by 177Lu-Dotatate include combinations of PRRT with radiosensitizers such as heat shock protein 90 inhibitors, hedgehog inhibitors, chemotherapy combinations, and triapine. Many of these combinations have just begun to be tested clinically. With regards to novel RTKIs, some of the ones which have demonstrated potent cytoreductive potential include cabozantinib and lenvatinib. Other RTKIs which are further along the clinical development spectrum and have demonstrated benefit in randomized trials include surufatinib and pazopanib. And though single-agent immune checkpoint inhibitors have not demonstrated significant anti-tumor activity in patients with GEP NETs, outside of certain biomarker selected subsets, somatostatin receptor-directed chimeric antigen receptor (CAR) T cells and vaccines such as SurVaxM, which targets survivin, represent two means through which NET-directed immunity may be modulated. The potential of these agents, if clinically realized, will likely improve outcomes for patients with well-differentiated GEP NETs.

Burden of injury along the development spectrum: associations between the Socio-demographic Index and disability-adjusted life year estimates from the Global Burden of Disease Study 2017

BackgroundThe epidemiological transition of non-communicable diseases replacing infectious diseases as the main contributors to disease burden has been well documented in global health literature. Less focus, however, has been given to the relationship between sociodemographic changes and injury. The aim of this study was to examine the association between disability-adjusted life years (DALYs) from injury for 195 countries and territories at different levels along the development spectrum between 1990 and 2017 based on the Global Burden of Disease (GBD) 2017 estimates.MethodsInjury mortality was estimated using the GBD mortality database, corrections for garbage coding and CODEm—the cause of death ensemble modelling tool. Morbidity estimation was based on surveys and inpatient and outpatient data sets for 30 cause-of-injury with 47 nature-of-injury categories each. The Socio-demographic Index (SDI) is a composite indicator that includes lagged income per capita, average educational attainment over age 15 years and total fertility rate.ResultsFor many causes of injury, age-standardised DALY rates declined with increasing SDI, although road injury, interpersonal violence and self-harm did not follow this pattern. Particularly for self-harm opposing patterns were observed in regions with similar SDI levels. For road injuries, this effect was less pronounced.ConclusionsThe overall global pattern is that of declining injury burden with increasing SDI. However, not all injuries follow this pattern, which suggests multiple underlying mechanisms influencing injury DALYs. There is a need for a detailed understanding of these patterns to help to inform national and global efforts to address injury-related health outcomes across the development spectrum.

Image Processing Techniques Aiding Smart Agriculture

With the ever-increasing load of satiating the agricultural demands, the transition of the orthodox methods into smart ones is inevitable. The agriculture sector for long has served as a momentous source of livelihood for many globally. It is arguably a major topic for nations of the development spectrum, contributing towards their export earnings and aiding in their GDP assessment. Thus, it is quite conspicuous that nations would work towards its expansion. In congruence, the burgeoning population and its demands have posed a threat to the environment due to extensive exploitation of resources, which in turn is escalating towards the downfall of the quality and quantity of agricultural produces requiring a 70% increment in the produces by 2050 for sustainability. To combat such hurdles, developed techniques are being employed. Through a survey of existing literature, this chapter provides a comprehensive overview of various image processing means that could come in handy for ameliorating the present scenario and shows their implied extension in the smart farming world.

Effect of Ownership on Firm Performance in Selected G-20 Countries Across the Development Spectrum.

This study investigates the effect of ownership on firm performance of state-owned and non-state-owned enterprises in elected G20 countries and across the development spectrum. Annual financial and accounting data from the period 2011-2015 are compiled for 252, state-owned and 6503, non-state-owned enterprises. The empirical results show that state ownership and firm performance are negatively associated with selected G-20countries. This is also confirmed when countries are considered with respect to their level of development except for High-Income countries. The poor performance of state-owned enterprises in less developed countries can be justified by the argument that state-owned enterprises suffer from the intervention of self-oriented politicians, which leads to lower-than-expected performance.

Implications of Food Subsistence for Monetary Policy and Inflation

The chapter introduces subsistence requirements in food consumption into a simple New Keynesian model with flexible food and sticky non-food prices. It shows how the endogenous structural transformation that results from subsistence affects the dynamics of the economy, the design of monetary policy, and the properties of inflation at different levels of development. A calibrated version of the model encompasses both rich and poor countries and broadly replicates the properties of inflation across the development spectrum, including the dominant role played by changes in the relative price of food in poor countries. The authors derive a welfare-based loss function for the monetary authority and show that optimal policy calls for complete (in some cases near-complete) stabilization of sticky-price non-food inflation, despite the presence of a food-subsistence threshold. Subsistence amplifies the welfare losses of policy mistakes, however, raising the stakes for monetary policy at earlier stages of development.