Abstract Human-induced climate change poses a major threat to the reliable water supply in many highly populated regions. Here we combine hydrological and climate model simulations to evaluate risks to the water supply under projected shifts in the climate at the Paris Agreement warming levels. Modelling the primary surface water sources for Melbourne, Australia, we project that the risk of severe water supply shortage to the climate-dependent portion of the system increases substantially as global warming increases from 1.5 °C to 2.0 °C. Risks are further exacerbated by increases in water demand but substantially ameliorated by supply augmentation from desalination. We demonstrate that reductions in precipitation, rising temperature and growth in water demand combine to substantially amplify the risk of severe water supply shortage under near-term global warming in the absence of a climate-independent supply. This risk amplification is not as apparent in assessments based on meteorological drought alone. With the diminishing opportunity of meeting the 1.5 °C Paris target, our study highlights the need to accelerate greenhouse gas mitigation efforts to reduce risks to climate dependent water supply systems.
<div>Abstract<p>Small molecule inhibitors targeting mutant EGFR are standard of care in non–small cell lung cancer (NSCLC), but acquired resistance invariably develops through mutations in EGFR or through activation of compensatory pathways such as cMet. Amivantamab (JNJ-61186372) is an anti-EGFR and anti-cMet bispecific low fucose antibody with enhanced Fc function designed to treat tumors driven by activated EGFR and/or cMet signaling. Potent <i>in vivo</i> antitumor efficacy is observed upon amivantamab treatment of human tumor xenograft models driven by mutant activated EGFR, and this activity is associated with receptor downregulation. Despite these robust antitumor responses <i>in vivo</i>, limited antiproliferative effects and EGFR/cMet receptor downregulation by amivantamab were observed <i>in vitro</i>. Interestingly, <i>in vitro</i> addition of isolated human immune cells notably enhanced amivantamab-mediated EGFR and cMet downregulation, leading to antibody dose-dependent cancer cell killing. Through a comprehensive assessment of the Fc-mediated effector functions, we demonstrate that monocytes and/or macrophages, through trogocytosis, are necessary and sufficient for Fc interaction-mediated EGFR/cMet downmodulation and are required for <i>in vivo</i> antitumor efficacy. Collectively, our findings represent a novel Fc-dependent macrophage-mediated antitumor mechanism of amivantamab and highlight trogocytosis as an important mechanism of action to exploit in designing new antibody-based cancer therapies.</p></div>
Abstract. High-resolution palaeoclimate proxies are fundamental to our understanding of the diverse climatic history of the Australian mainland, particularly given the deficiency in instrumental datasets spanning greater than a century. Annually resolved, tree-ring based proxies play a unique role in addressing limitations in our knowledge of interannual to multi-decadal temperature and hydroclimatic variability prior to the instrumental period. Here we present cross-dated ring-width (RW) and minimum blue-intensity (BI) chronologies spanning 70 years (1929 – 1998) for Podocarpus lawrencei Hook.f., the Australian mainland's only alpine conifer, based on nine full-disk cross-sections from Mount Loch in the Victorian Alps. Correlations with climate variables from observation stations and gridded data reveal a significant positive relationship between RW and mean monthly maximum temperatures in winter throughout central Victoria (r = 0.62, p < 0.001), and a significant negative correlation to winter precipitation (r = -0.51, p < 0.001). We also found significant negative correlations between RW and monthly snow depth at Spencer Creek in New South Wales (r = -0.60, p < 0.001). Of the assessed BI parameters, delta blue-intensity (ΔBI; the difference between early- and late-wood BI) displayed the greatest sensitivity to climate, with robust spatial correlations with mean October to December maximum and minimum monthly temperatures (r = -0.43, p < 0.001; r = -0.51, p < 0.001) and July precipitation (r = 0.44, p < 0.001), across large areas of northern Victoria. These promising findings highlight the utility of this species for future work. With the very limited availability of suitable long-lived and cross-datable species on the Australian mainland, these results have significant implications for advancing high-resolution palaeoclimate science in southeastern Australia and for improving our understanding of past climate in the region.
In this paper, we argue that current definitions of drought, especially in the context of small-scale agricultural production, are incomplete. We introduce the concept of 'technological drought' to account for crop failures, or reduced yields, that are the consequence of an inability to supplement root-zone moisture when there is a rainfall deficit. We use small-scale cropping in Bangladesh to illustrate the diversity of causes of technological drought, which can include shortages of fuel or electricity to operate pumps, problematically high costs to access irrigation infrastructure, or constrained access to pumps that have to be shared among multiple farmers. We argue that vulnerability to technological drought can be strongly conditioned by socio-economic conditions, and that its impact can be magnified when population growth and the demand for food mean that any decline in yield can have serious consequences for food security. We show that technological drought is a complex phenomenon, and can be differentiated from the more widely-recognised classes of drought (meteorological, hydrological, and agricultural) in multiple ways. In particular, technological drought exhibits an important dependence on the socio-economic context of agricultural production. It is perhaps most evident in developing economies, especially where agricultural output depends strongly on the capacity of individual farmers to manage crop water supply on small holdings. A case study from Bangladesh shows that technological drought can follow from even brief interruptions to monsoon rainfall during critical stages of crop growth, such that technological droughts can be distinguished from other forms of drought by their brevity.
Abstract Diverse characteristics of El Niño Southern Oscillation (ENSO) events challenge the traditional view of tropical coupled ocean-atmosphere systems. The probability of a transition from one type of event to another is influenced by multiple factors of which many are projected to change. Here we assess the likelihood of ENSO transitions in observations and climate models, including a distinction between events that peak in the Eastern Pacific (EP) and Central Pacific (CP). We find that the initial ENSO state influences the likelihood of certain transitions and that some transitions are not physically possible or stochastically likely. For example, transitions to CP events are more likely than EP events except from a neutral state. We also find that El Niños tend to occur as singular events compared to La Niñas. While consecutive El Niño and La Niña events of EP type are possible, opposing EP events do not occur in succession. We identify several transitions likely driven by internal dynamical processes including neutral conditions to El Niño, CP El Niño to another El Niño, EP El Niño to CP La Niña, CP La Niña to CP El Niño and La Niña, and EP La Niña to neutral and CP El Niño. Projections of future transitions show an increased probability of transitions to CP El Niño events while transitions to EP La Niña events become less frequent under a high-emissions scenario. Accordingly, transitions to these events become more and less likely, respectively. We also find changes in the likelihood of specific transitions in a warming world: consecutive CP El Niño events become more likely while EP El Niño events become less likely to transition into CP La Niña events. These changes are expected to occur as early as 2050 with some changes to be accelerated by the end of the 21st century.
Abstract The Australian monsoon delivers seasonal rain across a vast area of the continent stretching from the far northern tropics to the semi‐arid regions. This article provides a review of advances in Australian monsoon rainfall (AUMR) research and a supporting analysis of AUMR variability, observed trends, and future projections. AUMR displays a high degree of interannual variability with a standard deviation of approximately 34% of the mean. AUMR variability is mostly driven by the El Niño‐Southern Oscillation (ENSO), although sea surface temperature anomalies in the tropical Indian Ocean and north of Australia also play a role. Decadal AUMR variability is strongly linked to the Interdecadal Pacific Oscillation (IPO), partially through the IPO's impact on the strength and position of the Pacific Walker Circulation and the South Pacific Convergence Zone. AUMR exhibits a century‐long positive trend, which is large (approximately 20 mm per decade) and statistically significant over northwest Australia. The cause of the observed trend is still debated. Future changes in AUMR over the next century remain uncertain due to low climate model agreement on the sign of change. Recommendations to improve the understanding of AUMR and confidence in AUMR projections are provided. This includes improving the representation of atmospheric convective processes in models, further explaining the mechanisms responsible for AUMR variability and change. Clarifying the mechanisms of AUMR variability and change would aid with creating more sustainable future agricultural systems by increasing the reliability of predictions and projections. This article is categorized under: Paleoclimates and Current Trends > Modern Climate Change
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