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Flooding is an endemic global challenge with annual damages totalling billions of dollars. Impacts are felt most acutely in low- and middle-income countries, where rapid demographic change is driving increased exposure. These areas also tend to lack high-precision hazard mapping data with which to better understand or manage risk. To address this information gap a number of global flood models have been developed in recent years. However, there is substantial uncertainty over the performance of these data products. Arguably the most important component of a global flood model is the digital elevation model (DEM), which must represent the terrain without surface artifacts such as forests and buildings. Here we develop and evaluate a next generation of global hydrodynamic flood model based on the recently released FABDEM DEM. We evaluate the model and compare it to a previous version using the MERIT DEM at three study sites in the Central Highlands of Vietnam using two independent validation data sets based on a household survey and remotely sensed observations of recent flooding. The global flood model based on FABDEM consistently outperformed a model based on MERIT, and the agreement between the model and remote sensing was greater than the agreement between the two validation data sets.

We present a transparent and validated climate-conditioned catastrophe flood model for the UK, that simulates pluvial, fluvial and coastal flood risks at 1 arcsec spatial resolution (∼ 20–25 m). Hazard layers for 10 different return periods are produced over the whole UK for historic, 2020, 2030, 2050 and 2070 conditions using the UK Climate Projections 2018 (UKCP18) climate simulations. From these, monetary losses are computed for five specific global warming levels above pre-industrial values (0.6, 1.1, 1.8, 2.5 and 3.3 ∘C). The analysis contains a greater level of detail and nuance compared to previous work, and represents our current best understanding of the UK's changing flood risk landscape. Validation against historical national return period flood maps yielded critical success index values of 0.65 and 0.76 for England and Wales, respectively, and maximum water levels for the Carlisle 2005 flood were replicated to a root mean square error (RMSE) of 0.41 m without calibration. This level of skill is similar to local modelling with site-specific data. Expected annual damage in 2020 was GBP 730 million, which compares favourably to the observed value of GBP 714 million reported by the Association of British Insurers. Previous UK flood loss estimates based on government data are ∼ 3× higher, and lie well outside our modelled loss distribution, which is plausibly centred on the observations. We estimate that UK 1 % annual probability flood losses were ∼ 6 % greater for the average climate conditions of 2020 (∼ 1.1 ∘C of warming) compared to those of 1990 (∼ 0.6 ∘C of warming), and this increase can be kept to around ∼ 8 % if all countries' COP26 2030 carbon emission reduction pledges and “net zero” commitments are implemented in full. Implementing only the COP26 pledges increases UK 1 % annual probability flood losses by 23 % above average 1990 values, and potentially 37 % in a “worst case” scenario where carbon reduction targets are missed and climate sensitivity is high.

The ExoClock project has been created to increase the efficiency of the Ariel mission. It will achieve this by continuously monitoring and updating the ephemerides of Ariel candidates, in order to produce a consistent catalog of reliable and precise ephemerides. This work presents a homogenous catalog of updated ephemerides for 450 planets, generated by the integration of ∼18,000 data points from multiple sources. These sources include observations from ground-based telescopes (the ExoClock network and the Exoplanet Transit Database), midtime values from the literature, and light curves from space telescopes (Kepler, K2, and TESS). With all the above, we manage to collect observations for half of the postdiscovery years (median), with data that have a median uncertainty less than 1 minute. In comparison with the literature, the ephemerides generated by the project are more precise and less biased. More than 40% of the initial literature ephemerides had to be updated to reach the goals of the project, as they were either of low precision or drifting. Moreover, the integrated approach of the project enables both the monitoring of the majority of the Ariel candidates (95%), and also the identification of missing data. These results highlight the need for continuous monitoring to increase the observing coverage of the candidate planets. Finally, the extended observing coverage of planets allows us to detect trends (transit-timing variations) for a sample of 19 planets. All the products, data, and codes used in this work are open and accessible to the wider scientific community.

The understanding of the nature and behavior of ice sheets in past warm periods is important for constraining the potential impacts of future climate change. The Pliocene warm period (between 3.264 and 3.025 Ma) saw global temperatures similar to those projected for future climates; nevertheless, Pliocene ice locations and extents are still poorly constrained. We present results from the efforts to simulate mid-Pliocene Greenland Ice Sheets by means of the international Pliocene Ice Sheet Modeling Intercomparison Project (PLISMIP). We compare the performance of existing numerical ice sheet models in simulating modern control and mid-Pliocene ice sheets with a suite of sensitivity experiments guided by available proxy records. We quantify equilibrated ice sheet volume on Greenland, identifying a potential range in sea level contributions from warm Pliocene scenarios. A series of statistical measures are performed to quantify the confidence of simulations with focus on inter-model and inter-scenario differences. We find that Pliocene Greenland Ice Sheets are less sensitive to differences in ice sheet model configurations and internal physical quantities than to changes in imposed climate forcing. We conclude that Pliocene ice was most likely to be limited to the highest elevations in eastern and southern Greenland as simulated with the highest confidence and by synthesizing available regional proxies; however, the extent of those ice caps needs to be further constrained by using a range of general circulation model (GCM) climate forcings.

[This corrects the article DOI: 10.1371/journal.pone.0094703.].

Follicular lymphoma can transform to a more aggressive histology. Here, the authors use bulk and single cell analysis to create a 26 marker panel which could be used to profile FL samples and predict the risk of transformation using flow cytometry.

The combination of dabrafenib and trametinib is a well-established treatment for BRAF-mutated melanoma. However, the effectiveness of this approach may be hindered by the development of treatment-related pyrexia syndrome, which occurs in at least 50% of treated patients. Without appropriate intervention, pyrexia syndrome has the potential to worsen and can result in hypotension secondary to dehydration and associated organ-related complications. Furthermore, premature treatment discontinuation may result in a reduction in progression-free and overall survival. Despite existing guidance, there is still a wide variety of therapeutic approaches suggested in the literature for both the definition and management of dabrafenib and trametinib-related pyrexia. This is reflected in the practice variation of its prevention and treatment within and between Canadian cancer centres. A Canadian working group was formed and consensus statements were constructed based on evidence and finalised through a two-round modified Delphi approach. The statements led to the development of a pyrexia treatment algorithm that can easily be applied in routine practice. The Canadian working group consensus statements serve to provide practical guidance for the management of dabrafenib and trametinib-related pyrexia, hopefully leading to reduced discontinuation rates, and ultimately improve patients’ quality of life and cancer-related outcomes.

A spinal extradural arachnoid cyst (SEAC) is a rare condition which can lead to back pain, radiculopathy, and compressive myelopathy. It accounts for approximately 1% of spinal tumours. The exact aetiology of SEACs is not well understood; however, this study is supportive of a traumatic aetiology of this disease in addition to supporting a uni-directional valve as a mechanism of CSF accumulation. The purpose of this study is to review the presentation, work-up, treatment and postoperative course of a patient with SEAC. We present the case of a 40-year-old male with a history of trauma who developed a SEAC and was treated surgically at our unit. Although a rare disease, we highlight the importance of early diagnosis and surgical treatment as it is a surgically curable disease with a good postoperative prognosis.

Abstract The COVID‐19 pandemic has been transformative for healthcare and medical education. Physician trainees and the education system that serves them adapted quickly so that trainees could finish the academic year on time and advance to the next phase of training without compromising clinical competency or public safety. Systemic changes have had the most significant impact on telemedicine training, virtual learning, secure testing, and the interview process for residency and fellowship training positions. Trainees are now getting regular, supervised practice experience with telemedicine. Some secure testing is being done remotely, without jeopardizing examination test items or trainee assessment. Attending physicians are experimenting with novel ways to engage learners with video for virtual rounds to keep the rounding team safe. Finally, the interview process for medical school, residency, and fellowship programs, which has traditionally been an expensive and travel‐laden process, has been made completely virtual for the first time ever. These changes have disadvantages, including a lack of social connection, potential distraction when learning remotely, and limited contact with a potential training program when interviewing by video. This perspective paper, written by a senior internal medicine resident, details his firsthand experience with these changes during the pandemic. It also looks forward to how the current changes will likely change medical education permanently and for the better.

The presence of islet autoantibodies and islet reactive T cells (T+) in adults with established type 2 diabetes (T2D) have been shown to identify those patients with more severe β-cell dysfunction. However, at what stage in the progression toward clinical T2D does islet autoimmunity emerge as an important component influencing β-cell dysfunction? In this ancillary study to the Restoring Insulin SEcretion (RISE) Study, we investigated the prevalence of and association with β-cell dysfunction of T+ and autoantibodies to the 65 kDa glutamic acid decarboxylase antigen (GADA) in obese pre-diabetes adults with impaired glucose tolerance (IGT) and recently diagnosed treatment naïve (Ndx) T2D. We further investigated the effect of 12 months of RISE interventions (metformin or liraglutide plus metformin, or with 3 months of insulin glargine followed by 9 months of metformin or placebo) on islet autoimmune reactivity. We observed GADA(+) in 1.6% of NdxT2D and 4.6% of IGT at baseline, and in 1.6% of NdxT2D and 5.3% of IGT at 12 months, but no significant associations between GADA(+) and β-cell function. T(+) was observed in 50% of NdxT2D and 60.4% of IGT at baseline, and in 68.4% of NdxT2D and 83.9% of IGT at 12 months. T(+) NdxT2D were observed to have significantly higher fasting glucose (p = 0.004), and 2 h glucose (p = 0.0032), but significantly lower steady state C-peptide (sscpep, p = 0.007) compared to T(−) NdxT2D. T(+) IGT participants demonstrated lower but not significant (p = 0.025) acute (first phase) C-peptide response to glucose (ACPRg) compared to T(−) IGT. With metformin treatment, T(+) participants were observed to have a significantly lower Hemoglobin A1c (HbA1c, p = 0.002) and fasting C-peptide (p = 0.002) compared to T(−), whereas T(+) treated with liraglutide + metformin had significantly lower sscpep (p = 0.010) compared to T(−) participants. In the placebo group, T(+) participants demonstrated significantly lower ACPRg (p = 0.001) compared to T(−) participants. In summary, T(+) were found in a large percentage of obese pre-diabetes adults with IGT and in recently diagnosed T2D. Moreover, T(+) were significantly correlated with treatment effects and β-cell dysfunction. Our results demonstrate that T(+) are an important component in T2D.

Globally, lightning causes significant injury, death, and damage to infrastructure annually. In comparison to the rest of the world, South Africa has one of the highest incidences of lightning-related injuries and deaths. The latest available lightning detection techniques and technologies are reviewed and include current research in South Africa and South Africa’s lightning detection challenges. Technological advances have contributed towards improving lightning detection and monitoring activities in many countries. South Africa has made considerably more progress in the field of lightning research than other African countries and possesses one of the three ground-based lightning detection networks in the southern hemisphere. However, despite these developments, rural communities in South Africa, and indeed in Africa, remain vulnerable to lightning, the occurrence of which is predicted to increase with climate change. A large proportion of the population of African countries resides in rural areas, where citizens participate in subsistence farming, and built infrastructure is not lightning safe. We recommend a call for the integration of indigenous and scientific knowledge as well as for the development of a participatory early warning system. Investigations into determining the most effective way to utilise existing monitoring networks – but with warning dissemination to rural communities – are also required. Lastly, future research on the development of lightning-safe rural dwellings or shelters, especially in lightning prone areas, is needed. Significance: • Climate change projections of increases in lightning incidence highlight an increased risk for vulnerable communities. • There is a lack of literature focusing on lightning detection within rural communities. • Technological advances now allow for better dissemination of lightning information and early warning within rural communities. • The South African Lightning Detection Network is operational at a national level; however, there is no dissemination at a local level. • There are currently no recommended design guidelines for informal dwellings and no safety protocols for rural communities.

Cardiac infection with Toxocara is rarely diagnosed, especially in children, and corresponding cardiac magnetic resonance imaging (CMR) has not been reported. We present a probable case, a 9-year-old girl with myopericarditis, eosinophilia, positive Toxocara serology, and CMR findings consistent with myocardial edema.

Prostate cancer is one of the most prevalent cancers worldwide, particularly affecting men living a western lifestyle and of African descent, suggesting risk factors that are genetic, environmental, and socioeconomic in nature. In the USA, African American (AA) men are disproportionately affected, on average suffering from a higher grade of the disease and at a younger age compared to men of European descent (EA). Fusion genes are chimeric products formed by the merging of two separate genes occurring as a result of chromosomal structural changes, for example, inversion or trans/cis-splicing of neighboring genes. They are known drivers of cancer and have been identified in 20% of cancers. Improvements in genomics technologies such as RNA-sequencing coupled with better algorithms for prediction of fusion genes has added to our knowledge of specific gene fusions in cancers. At present AA are underrepresented in genomic studies of prostate cancer. The primary goal of this study was to examine molecular differences in predicted fusion genes in a cohort of AA and EA men in the context of prostate cancer using computational approaches. RNA was purified from prostate tissue specimens obtained at surgery from subjects enrolled in the study. Fusion gene predictions were performed using four different fusion gene detection programs. This identified novel putative gene fusions unique to AA and suggested that the fusion gene burden was higher in AA compared to EA men.