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The increasing frequency and intensity of heavy rainfall events driven by climate change poses challenges for flood risk management. In this study, we use a high-resolution, convection-permitting ensemble from the UK climate projections local dataset to explore how the spatiotemporal characteristics of heavy rainfall events may evolve across the UK. Adopting an event-based framework, we analyse 5 km hourly rainfall data from 12 ensemble members and compare changes in future rainfall events to those derived from applying intensity-based scaling factors alone. This comparison allows us to identify aspects of rainfall change that are not captured by shifts in intensity distributions. Our results show that short-duration winter events become increasingly localised, with peak intensities increasing by up to 47%, amplifying flash flood potential. In summer, rainfall events exhibit expanded spatial extents—expanding by 25%–40%—magnifying total precipitation volumes. While we find small changes in the number of clustered events (i.e. heavy rainfall events that occur within a 21 day window), there are large changes to the contribution these have to seasonal precipitation, particularly in summer (7%–11% in the baseline to 11%–16% in future period). These findings highlight new insights into how heavy rainfall may change under future climate conditions, identifying aspects of change beyond intensity increases alone that are relevant for informing current practice for flood risk estimation.

Estimates of current and future population exposure to both coastal and inland flooding do not exist consistently in all Small Island Developing States (SIDS), despite these being some of the places most at risk to climate change. This has primarily been due to a lack of suitable or complete data. In this paper, we utilise a ∼30 m global hydrodynamic flood model to estimate population exposure to coastal and inland flood hazard in all SIDS under present day, as well as under low, intermediate, and very high emissions climate change scenarios (SSP1-2.6, SSP2-4.5 and SSP5-8.5). Our analysis shows that present day population exposure to flooding in SIDS is high (19.5% total population: 100 year flood hazard), varies widely depending on the location (3%–66%), and increases under all three climate scenarios—even if global temperatures remain below 2 °C warming (range in percentage change between present day and SSP1-2.6: −4.5%–44%). We find that levels of flood hazard and population exposure are not strongly linked, and that indirect measures of exposure in common vulnerability or risk indicators do not adequately capture the complex drivers of flood hazard and population exposure in SIDS. The most exposed places under the lowest climate change scenario (SSP1-2.6) continue to be the most exposed under the highest climate change scenario (SSP5-8.5), meaning investment in adaptation in these locations is likely robust to climate scenario uncertainty.

The diversity of flood‐generating mechanisms superimposed on catchment physiographic features with non‐stationary meteorological drivers makes future flood hazard assessment a grand challenge. To date, many studies have examined patterns in rainfall and streamflow, but far fewer have investigated trends in the other drivers of flooding. The complex transfer function between precipitation and flooding makes it potentially misleading to simply look at the change in rainfall to express the hazard. Furthermore, there are very few studies that have directly used output from km‐scale climate models in flood modeling. Coarse resolution climate data sets may not credibly resolve local climate and weather extremes. Changes in rainfall distribution and antecedent moisture over extended time periods due to climate change have so far been ignored when assessing urban pluvial flood risk. In this paper, an urban flood hazard assessment framework using the latest 2.2 km resolution UK Climate Projections Local is proposed. Global warming induced changes in pluvial flood risks under RCP8.5 are projected, focusing on the impact of changing precipitation patterns and soil moisture dynamics on flood generation. Results indicate a strong increase in the frequency of occurrence of extreme floods, and the resultant future (2060–2080) annual flood volume is expected to increase up to 52.6% relative to 1980–2000 over a major UK urban region, and these patterns are likely to hold more generally elsewhere in the UK. Shifts to a later occurrence of extreme flooding is identified under global warming. Previous studies that have neglected soil moisture dynamics are unlikely to give accurate flood estimates. Plain Language Summary The future flood hazard status over the major UK urban region of Bristol (domain size ∼746 km2) is evaluated using the latest 12‐member UK Climate Projections Local ensemble rainfall data set at the hourly and kilometer scale. A total of 30,098 rainfall events from an equivalent 720 years of climate data are identified and used for flood modeling. Impact of changing precipitation pattern and soil moisture dynamics on surface water floods are evaluated, and the interaction between precipitation, inundation, infiltration, and soil wetness are handled simultaneously at a spatial resolution of ∼30 m or less using an improved hydrodynamic model (LISFLOOD‐FP). Our findings highlight a shift toward a later seasonal occurrence of extreme flooding under global warming. Specifically, a large proportion of future extreme flood hazards is projected to manifest in December, contrasting with historical trends where most extreme events occurred in November. Extreme precipitation can be magnified in rainy seasons due to amplified moisture convergence, while in dry periods limited moisture availability may offset precipitation increases. Despite an overall increase in the total annual rainfall volume, the future summer is anticipated to be much drier due to limited rainfall availability, leading to a further reduction in soil moisture availability. Key Points Shifts to a later seasonal occurrence of extreme flooding is identified under global warming in the UK Increase in annual total rainfall leads to a disproportionate rise in the resultant flood volume Impact of the antecedent soil moisture on flood generation shows seasonality

International humanitarian organisations increasingly turn to forecast teams to support the coordination of efforts to respond to disasters caused by hazards such as tropical cyclones and large‐scale fluvial floods. Such disasters often occur where there is limited local capacity or information available to support decision making and so global forecasting capacity is utilised to provide impact‐based flood forecast bulletins. A multidisciplinary team joined together to provide forecast bulletins and expertise for such events through the UK Foreign and Commonwealth Development Office (FCDO). This paper captures the successes and challenges from two cyclones: Hurricane Iota in Central America (November 2020) and Cyclone Eloise in Mozambique (January 2021). Recommendations to improve global forecasting systems are made which will benefit the international community of researchers and practitioners involved in disaster prediction, anticipatory action and response. These include the need for additional data and expertise to support the interpretation of global models, clear documentation to support decision makers faced with multiple sources of information, and the development of user relevant metrics to assess the skill of global models. We discuss the value of effective partnerships and improving synergies between global models and local contexts, highlighting how global forecasting can help build local forecasting capability.

This study aimed to elucidate the role of ELF3, an ETS family member in normal prostate growth and prostate cancer. Silencing ELF3 in both benign prostate (BPH‐1) and prostate cancer (PC3) cell lines resulted in decreased colony‐forming ability, inhibition of cell migration and reduced cell viability due to cell cycle arrest, establishing ELF3 as a cell cycle regulator. Increased ELF3 expression in more advanced prostate tumours was shown by immunostaining of tissue microarrays and from analysis of gene expression and genetic alteration studies. This study indicates that ELF3 functions not only as a part of normal prostate epithelial growth but also as a potential oncogene in advanced prostate cancers. In the prostate, ELF3 is expressed in committed basal (CB) cells but not stem cells (SC), transit amplifying (TA) cells or luminal (L) cells. Using siRNA to knockdown ELF3 expression results in cell cycle arrest, reduced colony formation and reduced wound healing. ELF3 is expressed in some high grade cancers and there is evidence for ELF3 amplification in metastatic cancers.

Loss of latexin (LXN) expression negatively correlates with the prognosis of several human cancers. Despite association with numerous processes including haematopoietic stem cell (HSC) fate, inflammation and tumour suppression, a clearly defined biological role for LXN is still lacking. Therefore, we sought to understand LXN expression and function in the normal and malignant prostate to assess its potential as a therapeutic target. Our data demonstrate that LXN is highly expressed in normal prostate luminal cells but downregulated in high Gleason grade cancers. LXN protein is both cytosolic and secreted by prostate cells and expression is directly and potently upregulated by all-trans retinoic acid (atRA). Whilst overexpression of LXN in prostate epithelial basal cells did not affect cell fate, LXN overexpression in the luminal cancer line LNCaP reduced plating efficiency. Transcriptome analysis revealed that LXN overexpression had no direct effects on gene expression but had significant indirect effects on important genes involved in both retinoid metabolism and IFN-associated inflammatory responses. These data highlight a potential role for LXN in retinoid signaling and inflammatory pathways. Investigating the effects of LXN on immune cell function in the tumour microenvironment (TME) may reveal how observed intratumoural loss of LXN affects the prognosis of many adenocarcinomas.

Flooding associated with Hurricane Maria in 2017 had devastating consequences for lives and livelihoods in Puerto Rico. Yet, an understanding of current and future flood risk on small islands like Puerto Rico is limited. Thus, efforts to build resilience to flooding associated with hurricanes remain constrained. Here, we take an event set of hurricane rainfall estimates from a synthetic hurricane rainfall simulator as the input to an event-based rainfall-driven flood inundation model using the hydrodynamic code LISFLOOD-FP. Validation of our model against high-water-mark data for Hurricane Maria demonstrates the suitability of this model for estimating flood hazard in Puerto Rico. We produce event-based flood hazard and population exposure estimates for the present day and the future under the 1.5 and 2 ∘C Paris Agreement goals. Population exposure to flooding from hurricane rainfall in Puerto Rico for the present-day climate is approximately 8 %–10 % of the current population for a 5-year return period, with an increase in population exposure to flooding by 2 %–15 % and 1 %–20 % under 1.5 and 2 ∘C futures (5-year return period). This research demonstrates the significance of the 1.5 ∘C Paris Agreement goal for Small Island Developing States, providing the first event-based estimates of flooding from hurricane rainfall under climate change for a small island.

The ETS transcription factor family members are involved in multiple cancers, including prostate cancer. Whilst extensive literature exists on the highly prevalent TMPRSS2-ERG gene fusion, the role of other ETS factors in prostate cancer is less well understood. ELF3 has been ascribed both oncogenic and tumour suppressive roles in prostate cancer and has been highlighted as a regulator of epithelial cell differentiation in other tissues. The overarching aim of this project was to elucidate the role of ELF3 in the context of both normal prostate development and prostate cancer. This study details an extensive expression profile of ELF3 in prostate epithelial cell lines, primary prostate cell subpopulations and prostate tissue. ELF3 expression was restricted to the basal compartment of epithelial glands, specifically to the committed basal cell subpopulation of the basal epithelial hierarchy. Appropriate cell models were used to investigate the role of ELF3 in the prostate. By silencing ELF3 in BPH-1 and PC3 cells, ELF3 was established as a regulator of the cell cycle. This manifested as a decrease in colony forming ability, migration and cell viability caused by G2 cell cycle arrest. Furthermore, manipulating ELF3 expression altered the differentiation status of cell lines and primary cells, highlighting that a balance of ELF3 expression is required to maintain proper differentiation of the epithelial hierarchy. Finally, a possible link of ELF3 to more advanced prostate tumours using tissue microarray analysis, a potential association with neuroendocrine differentiation and putative survival advantage of ELF3 expression in cancer vs normal cells, was identified. These results suggest that ELF3 acts as an oncogene in the prostate cancer setting. However, its importance in normal prostate epithelial cell growth and differentiation has also been demonstrated. Work should now focus on identifying appropriate downstream effectors that could be targeted to exploit these properties for prostate cancer treatment.

Phospholipases D1 and D2 (PLD1/2) have been implicated in tumorigenesis. We previously detected higher expression of PLD in the nuclei of patient-derived prostate cancer (PCa) cells and prostate cancer cell lines. Here we have examined whether PLD1 or PLD2 are associated with the nuclear matrix and influence cell cycling. PLD1/PLD2 were detected by qualitative immunofluorescence in cultured PCa cells and extracted with a standardised protocol to reveal nuclear matrix-associated proteins. The effects of isoform-specific inhibition of PLD1or PLD2 on PCa cell cycle progression were analysed by flow cytometry. PLD2 mainly co-localised with the nucleolar marker fibrillarin in PCa cells. However, even after complete extraction, some PLD2 remained associated with the nuclear matrix. Inhibiting PLD2 effectively reduced PCa cell cycling into and through S phase. In contrast, PLD1 inhibition effects were weaker, and a subpopulation of cycling patient-derived PCa cells was unaffected by PLD1 inhibition. When associated with the nuclear matrix PLD2 could generate phosphatidic acid to regulate nuclear mTOR and control downstream transcriptional events. The association of PLD2 with the nucleolus also implies a role in stress regulation. The cell cycling results highlight the importance of PLD2 inhibition as a novel potential prostate cancer therapeutic mechanism by differential regulation of cell proliferation. Competing Interest Statement The authors have declared no competing interest.

ObjectivesTo estimate the prevalence of dementia and mild cognitive impairment (MCI) in the older prisoner population in England and Wales and to establish risk of harm to self and others, activity of daily living needs and social networks of prisoners with likely MCI and dementia.DesignWe screened 869 older prisoners (aged 50 years and older) using the Montreal Cognitive Assessment (MoCA). Participants testing positive on the MoCA (≤23) were interviewed using the Addenbrooke’s Cognitive Examination, Third Revision (ACE-III) and a range of standardised assessments were used to assess risks of externalised violence and of self-harm; activities of daily living needs; mental health needs; history and symptoms of brain injury (if applicable) and social networks.SettingThe sample was drawn randomly from women’s prisons (n=10) and a representative range of adult men’s prisons (n=11) across England and Wales.ParticipantsParticipants were aged 50 or over and resident in one of the participating prison establishments on the study’s census day.Main outcome measureACE-III.ResultsWe recruited 596 men and 273 women prisoners. Across the whole sample of older prisoners, the prevalence of dementia was 7.0% (95% CI 5.5%, 8.9%) (when weighted for sex and age), with the highest prevalence found among prisoners aged 70 years and older at 11.8% (95% CI 8.0%, 17.1%). The prevalence of dementia for men was 7.0% (95% CI 5.2%, 9.4%) and for women was 6.0% (95% CI 3.8%, 9.5%). Only two individuals (3%) who screened positively on the MoCA had a diagnosis of dementia in their prison healthcare notes, suggesting current under-recognition. The prevalence of MCI was 0.8% (95% CI 0.4% to 1.7%, weighted by age). Of those who screened positively on the MoCA, 32 (46%) participants had a high or very high risk of harm to self or others, and 70 (35%) had no friends with whom they could talk to about private matters or to call on for help (n=35, 50%).ConclusionsApproximately 1020 older adults living in prison have symptoms of likely dementia, and service provision for this group is inadequate.