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The El Nino Southern Oscillation (ENSO) influences the weather around the world and, therefore, has strong impacts on society. Here, the authors show that ENSO is associated with child nutrition in many countries, with warmer El Niño conditions leading to more child undernutrition in large parts of the developing world.

Legislation passed in 2007 by the U.S. Congress increased by about 1.3 billion bushels the net amount of corn required to be processed annually into ethanol for motor-fuel use. We estimate that corn prices were about 30% higher from 2006 to 2014 than they would have been without this demand increase. We develop a partially identified structural vector autoregression model. Our identification strategy is unique in the literature because it enables us to estimate the effects of transitory shocks, such as weather, separately from the effects of persistent shocks, such as the increased ethanol mandate. Moreover, by only partially identifying our model, we show how to generate robust conclusions without strong identifying assumptions.

This paper estimates the role of agronomic inputs in cereal yield improvements and the consequences for countries' processes of structural change. The results suggest a clear role for fertilizer, modern seeds and water in boosting yields. We then test for respective empirical links between agricultural yields and economic growth, labor share in agriculture and non-agricultural value added per worker. The identification strategy includes a novel instrumental variable that exploits the unique economic geography of fertilizer production and transport costs to countries' agricultural heartlands. We estimate that a half ton increase in staple yields generates a 14 to 19 percent higher GDP per capita and a 4.6 to 5.6 percentage point lower labor share in agriculture five years later. The results suggest a strong role for agricultural productivity as a driver of structural change.

Reducing the global health burden of malaria is complicated by weak reporting systems for infectious diseases and a paucity of vital statistics registration. This limits our ability to predict changes in malaria health burden intensity, target antimalarial resources where needed, and identify malaria impacts in retrospective data. We refined and deployed a temporally and spatially varying Malaria Ecology Index (MEI) incorporating climatological and ecological data to estimate malaria transmission strength and validate it against cross-sectional serology data from 39,875 children from seven sub-Saharan African countries. The MEI is strongly associated with malaria burden; a 1 standard deviation higher MEI is associated with a 50-117% increase in malaria risk and a 3-5 g/dL lower level of Hg. Results show that the relationship between malaria ecology and disease burden is attenuated with sufficient coverage of insecticide treated nets (ITNs) or indoor residual spraying (IRS). Having both ITNs and IRS reduce the added risk from adverse malaria ecology conditions by half. Readily available climate and ecology data can be used to estimate the spatial and temporal variation in malaria disease burden, providing a feasible alternative to direct surveillance. This will help target resources for malaria programs in the absence of national coverage of active case detection systems, and facilitate malaria research using retrospective health data.

This essay suggests that Wittgenstein's philosophy can be read as an example of what Hadot and Foucault call spiritual practices, and it uses that reading to cast light on the way certain experiences can change one's life. These experiences could as simple as reading a book or even, as might be the case with Thoreau, living alone by a pond. The essay concentrates on the spiritual practices of the "Tractatus," but it uses the Investigations' discussion of noticing a change in aspect to characterise these life-altering experiences. Wittgenstein sought to transform our vision of the world and to induce a metamorphosis in our being by weaning us from the expectation that philosophy will solve the problem of life and by pointing us in the direction of a pedagogy of things.

Background: The effects of Aquatic High-Intensity Interval Training (AHIIT) and resistive AHIIT (Resistive AHIIT) to improve metabolic responses were not yet known. Objective: This study was to compare the metabolic responses and perceived effort in young healthy adults in a single session of AHIIT and resistive AHIIT. Methods: 20 healthy subjects (9 females, 11 males) performed a stationary running at a matched exercise intensity prior AHIIT and resistive AHIIT [10 × 1-min bouts of stationary running at 90% maximum heart rate (HR max) separated by 1-min active recovery] to examine the metabolic and cardiometabolic outcomes. Mixed effects models were applied to analyze the effects of group, time, and the interaction between group and time on both outcomes. The level of correlations between metabolic variables was checked by Pearson's linear correlation. Results: There are significant differences on pre and post resting energy expenditure (REE) within both AHIIT and resistive AHIIT groups (p < 0.01) respectively as well as the subjective rate of perceived exertion (RPE) (p < 0.01) within RAHIIT group. A moderate correlation found on respiratory exertional ratio (RER) and RPE in resistive AHIIT (r = 0.534). No significant differences between groups in terms of HR max, mean heart rate (HR mean), peak oxygen consumption (VO2 peak) and total energy expenditure (TEE) (p = 0.50, p = 0.48, p = 0.81, p = 0.59). Conclusion: Resistive AHIIT provides comparable benefits of metabolic outcomes with AHIIT. Comparable results allowed AHIIT and resistive AHIIT prescriptions precisely. [ABSTRACT FROM AUTHOR]

Malignant tumors, characterized by uncontrolled cell proliferation, are a leading global health challenge, responsible for over 9.7 million deaths in 2022, with new cases expected to rise to 35 million annually by 2050. Immunotherapy is preferred to other cancer therapies, offering precise targeting of malignant cells while simultaneously strengthening the immune system's complex responses. Advances in this novel field of science have been closely linked to a deeper knowledge of tumor biology, particularly the intricate interplay between tumor cells, the immune system, and the tumor microenvironment (TME), which are central to cancer progression and immune evasion. This review offers a comprehensive analysis of the molecular mechanisms that govern these interactions, emphasizing their critical role in the development of effective immunotherapeutic products. We critically evaluate the current immunotherapy approaches, including cancer vaccines, adoptive T cell therapies, and cytokine‐based treatments, highlighting their efficacy and safety. We also explore the latest advancements in combination therapies, which synergistically integrate multiple immunotherapeutic strategies to overcome resistance and enhance therapeutic outcomes. This review offers key insights into the future of cancer immunotherapy with a focus on advancing more effective and personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Freshwater connectivity and the associated flow regime are critical components of the health of freshwater ecosystems. When freshwater ecosystems are fragmented, the movements and flows of species, nutrients, sediments, and water are altered, changing the natural dynamics of freshwater ecosystems. The consequences of these changes include declines and loss of freshwater species populations and freshwater ecosystems, and alterations in the delivery of certain ecosystem services, such as fisheries, buffering of flood events, healthy deltas, recreational and cultural values, and others. Measures exist that can maintain and restore connectivity or mitigate against its loss in the face of constructed barriers or other habitat alterations. These measures include system-scale planning for energy and water resources that includes options for limiting loss of freshwater connectivity; putting in place protections for keeping critically important freshwater habitats connected; mitigating impacts on freshwater ecosystems via barrier design, fish passage, or implementation of environmental flows; and restoring freshwaters via barrier removal and reconnection of rivers, wetlands, and floodplains and via active management of groundwater recharge. We present case studies of measures applied in Europe, Asia, Africa, and the Americas and reflect on the next generation of innovation needed to further enhance and advance the implementation of restoration and protection and the mitigation of freshwater connectivity impacts. [ABSTRACT FROM AUTHOR]

Environmental flows (e-flows) aim to mitigate the threat of altered hydrological regimes in river systems and connected waterbodies and are an important component of integrated strategies to address multiple threats to freshwater biodiversity. Expanding and accelerating implementation of e-flows can support river conservation and help to restore the biodiversity and resilience of hydrologically altered and water-stressed rivers and connected freshwater ecosystems. While there have been significant developments in e-flow science, assessment, and societal acceptance, implementation of e-flows within water resource management has been slower than required and geographically uneven. This review explores critical factors that enable successful e-flow implementation and biodiversity outcomes in particular, drawing on 13 case studies and the literature. It presents e-flow implementation as an adaptive management cycle enabled by 10 factors: legislation and governance, financial and human resourcing, stakeholder engagement and co-production of knowledge, collaborative monitoring of ecological and social-economic outcomes, capacity training and research, exploration of trade-offs among water users, removing or retrofitting water infrastructure to facilitate e-flows and connectivity, and adaptation to climate change. Recognising that there may be barriers and limitations to the full and effective enablement of each factor, the authors have identified corresponding options and generalizable recommendations for actions to overcome prominent constraints, drawing on the case studies and wider literature. The urgency of addressing flow-related freshwater biodiversity loss demands collaborative networks to train and empower a new generation of e-flow practitioners equipped with the latest tools and insights to lead adaptive environmental water management globally. Mainstreaming e-flows within conservation planning, integrated water resource management, river restoration strategies, and adaptations to climate change is imperative. The policy drivers and associated funding commitments of the Kunming–Montreal Global Biodiversity Framework offer crucial opportunities to achieve the human benefits contributed by e-flows as nature-based solutions, such as flood risk management, floodplain fisheries restoration, and increased river resilience to climate change. [ABSTRACT FROM AUTHOR]

South Africa's inland fisheries are generally undervalued, though there is developing interest in the sector. Spring Grove Dam in the KwaZulu-Natal Midlands became operational as a water storage facility in 2013 to provide water to the growing urban population in the province. We assessed whether the impoundment could potentially support commercial fisheries as had been proposed during its design and construction. We conducted seasonal fish community surveys from 2020 to 2021 at sites along the impoundment and in the mainstem of the Mooi River which feeds into the impoundment. We recorded a total of nine fish species, including six non-native fishes with invasive characteristics. Only three of 10 expected native species were found, namely the KwaZulu-Natal yellowfish Labeobarbus natalensis, chubbyhead barb Enteromius anoplus and African longfin eel Anguilla mossambica. Catch per unit effort (CPUE) was low in the sampling surveys using mostly gillnets and fyke nets, and relatively low yields (14.97 tonnes yr-1) were subsequently calculated for the impoundment, making commercial fisheries unviable. However, the existing subsistence and recreational fisheries for non-native salmonids and the native L. natalensis would benefit by controlling the distribution range and abundances of non-native centrachids Micropterus spp. We offer recommendations and suggestions for management plans for Spring Grove Dam in the context of local fish diversity, a changing climate, further construction of water storage facilities on east-flowing rivers in the province, and a nationally neglected inland fishery industry. [ABSTRACT FROM AUTHOR]

Placental dysfunction can have catastrophic or barely discernible effects ranging from miscarriage to apparently normal birth. Here the authors present a comprehensive analysis of the human placental transcriptome and identify circular RNAs and piRNAs.

The broad determinants of fertility are thought to be reasonably well identified by demographers, though the detailed quantitative drivers of fertility levels and changes are less well understood. This paper uses a novel ecological index of malaria transmission to study the effect of child mortality on fertility. We find that temporal variation in the ecology of the disease is well-correlated to mortality, and pernicious malaria conditions lead to higher fertility rates. We then argue that most of this effect occurs through child mortality, and estimate the effect of child mortality changes on fertility. Our findings add to the literature on disease and fertility, and contribute to the suggestive evidence that child mortality reductions have a causal effect on fertility changes.

Microtubule-targeting agents (MTAs) are widely used anticancer agents, but toxicities such as neuropathy limit their clinical use. MTAs bind to and alter the stability of microtubules, causing cell death in mitosis. We describe DZ-2384, a preclinical compound that exhibits potent antitumor activity in models of multiple cancer types. It has an unusually high safety margin and lacks neurotoxicity in rats at effective plasma concentrations. DZ-2384 binds the vinca domain of tubulin in a distinct way, imparting structurally and functionally different effects on microtubule dynamics compared to other vinca-binding compounds. X-ray crystallography and electron microscopy studies demonstrate that DZ-2384 causes straightening of curved protofilaments, an effect proposed to favor polymerization of tubulin. Both DZ-2384 and the vinca alkaloid vinorelbine inhibit microtubule growth rate; however, DZ-2384 increases the rescue frequency and preserves the microtubule network in nonmitotic cells and in primary neurons. This differential modulation of tubulin results in a potent MTA therapeutic with enhanced safety.