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The UK has experienced recurring periods of hydrological droughts in the past, including the latest drought declared in summer 2022. Seasonal hindcasts, consisting of a large sample of plausible weather sequences, can be used to add value to existing approaches to water resources planning. In this study, the drivers of winter rainfall in the Greater Anglia region are investigated using the ECMWF SEAS5 hindcast dataset, which includes 2850 plausible winters across 25 ensemble members and 3 lead times. Four winter clusters were defined using the hindcast winters based on possible combinations of various atmospheric circulation indices (such as North Atlantic Oscillation, East Atlantic Pattern and the El-Niño Southern Oscillation). Using the 2022 drought as a case study, we demonstrate how storylines of the event could be created in autumn 2022 to provide an outlook of drought conditions and to explore plausible worst cases over winter 2022/23 and beyond. The winter clusters span a range of temperature and rainfall response in the Anglian region and represent circulation storylines that could have happened over winter 2022/23. Although winter 2022/23 has now passed, we aim to demonstrate the added value of this approach to provide outlooks during an ongoing event with a brief retrospective of how winter 2022/23 transpired. Storylines created from the hindcast winters were simulated using the GR6J catchment hydrological model and the groundwater level model Aquimod at selected catchments and boreholes in the Anglian region. Results show that drier than average winters characterised by predominantly NAO-/EA- and NAO+/EA- circulation patterns would result in the continuation of the drought with a high likelihood of below normal to low river flows across all selected catchments and boreholes by spring and summer 2023. Catchments in Norfolk are particularly vulnerable to a dry summer in 2023 as river flows are not estimated to recover to normal levels even with wet La Niña winters characterised predominantly by NAO-/EA+ and NAO+/EA+ circulation patterns due to insufficient rainfall to overcome previous dry conditions and the slow response nature of groundwater-dominated catchments. Storylines constructed in this way provide outlooks of ongoing events and supplement traditional weather forecasts to explore a wider range of plausible outcomes.

Hard functional and logic failures which are insensitive to temperature, voltage, or frequency have become increasingly difficult to debug in advanced technology nodes, especially when Photon Emission (PEM) analysis could not provide any leads and Dynamic Laser Stimulation (DLS) could not be used due to the nature of the failure (no pass/fail margin). Laser Voltage Imaging (LVI), which is an extension of the Laser Voltage Probing (LVP) technique, provides a visual map of active components that are toggling at a certain frequency. This technique is widely employed in scan chain debug due to its simplicity, efficiency, and accuracy. However, most of LVI applications in literature reviews only involve scan chain fault isolation. This paper will present alternative applications for LVI, apart from scan chain debug. One specific application is the debug of a broken signal path by sending a periodic signal as a stimulus to a GPIO pad and tracing the LVI signal through the path by frequency mapping. In this paper, the concept and methodology behind this fault isolation approach will be discussed in full detail. Furthermore, three case studies of different types of hard failures with different applications of LVI will also be presented: an IO functional failure, an ATPG (Automatic test pattern generation) SAF (Stuck At Fault) failure and a BSDL(Boundary scan description language) input interconnect failure, to illustrate how LVI could be deployed in fault isolation for those functional and logic hard failures.

Photon Emission Microscopy (PEM) analysis is one of the most common used FA techniques to identify the root cause of failures within ATPG scan logic due to its ease of setup and less invasive nature. While conducting photon emissions, the device is made to operate in the fail mode by running a production test vector to look for anomalous emissions or hot spots that could narrow down the area of interest (AOI) for subsequent Physical Failure Analysis (PFA). However, if there is no clue from emission analysis in the case of a hard failure with no sensitivity to voltage, frequency, or temperature, FA debug will be challenging. This paper shows how PEM analysis success may be further improved through logic state circuit study using a DFT ATPG diagnostic platform. Logic state truth table and its relative test pattern will be built based on the diagnostic data using in-house scripts, and the test program can then be changed to the required condition of the circuitry. With the altered logic state, new emission data can be collected, which could potentially reveal new clues to the investigation.

Much research has been carried out on the possible impacts of climate change for UK river flows. Catchment and national-scale studies since the early 1990s are here categorized into four modelling approaches: “top-down” GCM (Global Climate Model)-driven and probabilistic approaches and “bottom-up” stylised and scenario-neutral approaches. Early studies followed a stylised approach with a small number of model experiments focused on system sensitivity. GCM-driven approaches dominate since the mid-1990s and are scenario-led and “top-down”, but which incur the cascade of uncertainty which results in a large amount of information that may not be conducive to decision-making. The emergence of probabilistic projections aims to incorporate probabilistic information in navigating climate model uncertainty but remained “top-down” with challenges over its practical use for water resources planning. The scenario-neutral approach has clear roots in the early stylised approach with the aim to explore plausible futures beyond climate model projections and system sensitivity. A synthesis of studies employing each approach shows that the magnitude and sign of change in different hydrological variables remain uncertain between different regions of the UK. Comparison between studies is difficult due to their methodological differences and consequently different choices along the impact modelling chain, and with a notable geographic bias in catchment selection in southeast England. Major limitations for each approach include barriers to decision-making from wide uncertainty ranges, limited consideration of high-impact outcomes, and challenges in their application in water resources planning. These challenges represent priorities for future research using new “hybrid” approaches to produce complementary information to “top down” projections within a more “bottom-up” framework. Exploratory modelling, robust decision-making and storylines are examples of new approaches that have emerged. Key to the emerging approaches identified is a need to combine different modelling approaches to tackle different sources of uncertainty according to the intended aims of individual applications.

Spatially extensive multi-year hydrological droughts cause significant environmental stress. The UK is expected to remain vulnerable to future multi-year droughts under climate change. Existing approaches to quantify hydrological impacts of climate change often rely solely on global climate model (GCM) projections following different emission scenarios. This may miss out low-probability events with significant impacts. As a means of exploring such events, physical climate storyline approaches aim to quantify physically coherent articulations of how observed events could hypothetically have unfolded in alternative ways. This study uses the 2010–2012 drought, the most recent period of severe hydrological drought in the UK, as a basis and analyses storylines based on changes to (1) precondition severity, (2) temporal drought sequence, and (3) climate change. Evidence from multiple storylines shows that the maximum intensity, mean deficit, and duration of the 2010–2012 drought were highly influenced by its meteorological preconditions prior to drought inception, particularly for northern catchments at shorter timescales. The influence of progressively drier preconditions reflects both the spatial variation in drought preconditions and the role of physical catchment characteristics, particularly hydrogeology in the propagation of multi-year droughts. There are two plausible storylines of an additional dry year with dry winter conditions repeated either before the observed drought or replacing the observed dramatic drought termination confirm the vulnerability of UK catchments to a “third dry winter” storyline. Applying the UKCP18 climate projections, we find that drought conditions worsen with global warming with a mitigation of drought conditions by wetter winters in northern catchments at high warming levels. Comparison of the storylines with a benchmark drought (1975–1976) and a protracted multi-year drought (1989–1993) shows that, for each storyline (including the climate change storylines), drought conditions could have matched and exceeded those experienced during the past droughts at catchments across the UK, particularly for southern catchments. The construction of storylines based on observed events can complement existing methods to stress test UK catchments against plausible unrealised droughts.

Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible.

Uncertainty in climate change impacts on river discharge in the Upper Awash Basin, Ethiopia, is assessed using five MIKE SHE hydrological models, six CMIP5 general circulation models (GCMs) and two representative concentration pathways (RCP) scenarios for the period 2071–2100. Hydrological models vary in their spatial distribution and process representations of unsaturated and saturated zones. Very good performance is achieved for 1975–1999 (NSE: 0.65–0.8; r: 0.79–0.93). GCM-related uncertainty dominates variability in projections of high and mean discharges (mean: –34% to +55% for RCP4.5, – 2% to +195% for RCP8.5). Although GCMs dominate uncertainty in projected low flows, inter-hydrological model uncertainty is considerable (RCP4.5: –60% to +228%, RCP8.5: –86% to +337%). Analysis of variance uncertainty attribution reveals that GCM-related uncertainty occupies, on average, 68% of total uncertainty for median and high flows and hydrological models no more than 1%. For low flows, hydrological model uncertainty occupies, on average, 18% of total uncertainty; GCM-related uncertainty remains substantial (average: 28%).

Funder: The Swedish Esophageal Cancer Study was funded by grants (R01 CA57947-03) from the National Cancer Institute he California Tobacco Related Research Program (3RT-0122; and; 10RT-0251) Marit Peterson Fund for Melanoma Research. CIDR is supported by contract HHSN268200782096C, Gastroesophageal reflux disease (GERD) is caused by gastric acid entering the esophagus. GERD has high prevalence and is the major risk factor for Barrett’s esophagus (BE) and esophageal adenocarcinoma (EA). We conduct a large GERD GWAS meta-analysis (80,265 cases, 305,011 controls), identifying 25 independent genome-wide significant loci for GERD. Several of the implicated genes are existing or putative drug targets. Loci discovery is greatest with a broad GERD definition (including cases defined by self-report or medication data). Further, 91% of the GERD risk-increasing alleles also increase BE and/or EA risk, greatly expanding gene discovery for these traits. Our results map genes for GERD and related traits and uncover potential new drug targets for these conditions.

Epidemiologic studies have reported inconsistent results regarding an association between Parkinson disease (PD) and cutaneous melanoma (melanoma). Identifying shared genetic architecture between these diseases can support epidemiologic findings and identify common risk genes and biological pathways. Here, we apply polygenic, linkage disequilibrium-informed methods to the largest available case-control, genome-wide association study summary statistic data for melanoma and PD. We identify positive and significant genetic correlation (correlation: 0.17, 95% CI 0.10-0.24; P = 4.09 x 10(-06)) between melanoma and PD. We further demonstrate melanoma and PD-inferred gene expression to overlap across tissues (correlation: 0.14, 95% CI 0.06 to 0.22; P = 7.87 x 10(-04)) and highlight seven genes including PIEZO1, TRAPPC2L, and SOX6 as potential mediators of the genetic correlation between melanoma and PD. These findings demonstrate specific, shared genetic architecture between PD and melanoma that manifests at the level of gene expression.