Data_Sheet_1_A new drought model for disaster risk management in the Punjab, Sindh and Baluchistan provinces of Pakistan.PDF

Drought poses a continual threat to both lives and livelihoods in the Global South. Although the impact on food security from drought could be reduced through early release of funds, the humanitarian sector typically reacts to crises rather than anticipates them. A significant challenge lies in devising a drought monitoring and forecasting system that can function across environmentally and economically diverse regions. This is particularly evident in Pakistan, which encompasses environments ranging from fertile riverbeds to arid deserts. This paper details the development, implementation, and operation of an anticipatory drought Disaster Risk Financing (DRF) programme for the provinces of Punjab, Sindh, and Baluchistan in Pakistan. Key to the DRF development are a new yield model for the primary crop in the target season (winter wheat), and a novel forecasting system for four seasonal drought indicators - namely winter wheat yield, precipitation, normalised difference vegetation index (NDVI) and vegetation health index (VHI). Formal evaluations demonstrate that the forecasts are skillful up to 2 months in advance of the end of the season – enabling anticipatory release of funds. The work presented here is applicable beyond Pakistan. Indeed, the model and the methodologies are sufficiently broad and adaptable to be utilised in arid and semi-arid regions across the Global South.</p

Disentangling oncogenic amplicons in esophageal adenocarcinoma

Esophageal adenocarcinoma is a prominent example of cancer characterized by frequent amplifications in oncogenes. However, the mechanisms leading to amplicons that involve breakage-fusion-bridge cycles and extrachromosomal DNA are poorly understood. Here, we use 710 esophageal adenocarcinoma cases with matched samples and patient-derived organoids to disentangle complex amplicons and their associated mechanisms. Short-read sequencing identifies ERBB2, MYC, MDM2, and HMGA2 as the most frequent oncogenes amplified in extrachromosomal DNAs. We resolve complex extrachromosomal DNA and breakage-fusion-bridge cycles amplicons by integrating of de-novo assemblies and DNA methylation in nine long-read sequenced cases. Complex amplicons shared between precancerous biopsy and late-stage tumor, an enrichment of putative enhancer elements and mobile element insertions are potential drivers of complex amplicons’ origin. We find that patient-derived organoids recapitulate extrachromosomal DNA observed in the primary tumors and single-cell DNA sequencing capture extrachromosomal DNA-driven clonal dynamics across passages. Prospectively, long-read and single-cell DNA sequencing technologies can lead to better prediction of clonal evolution in esophageal adenocarcinoma