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Pulsed electric field (PEF) therapies employ punctuated energy delivery to kill cells in a volume of tissue through mechanisms that are not dependent on thermal processes. A key component to successful cardiac ablation procedures is ensuring the generation of transmural, contiguous ablation zones, which requires in-depth knowledge regarding treatment sizes for a given therapeutic application.In this study, a series of acute treatments were delivered to porcine ventricles, where triphenyl tetrazolium chloride (TTC) vitality stain was used to identify treatment effect sizes for the three focal monopolar CENTAURI PEF cardiac ablation energy settings.Treatment depths were 5.7, 7.2, and 8.2 mm for the 19, 22, and 25 A energy settings, respectively. Gross pathology indicated umbral zones of hemorrhage surrounded by pale avital TTC-negative-negative tissue, which contrasted significantly from radiofrequency ablation (RF) controls. Histologically, treatment zones are identified by regions of contraction band necrosis and cardiomyocytolysis, which contrasted with RF control lesions composed primarily of coagulation necrosis.Together, these data indicate the ability for focal monopolar PEF treatments to generate deep treatment zones in cardiac ablation without incurring the gross or histological coagulative characteristics of RF thermal lesions.

Accurate predictions of heavy precipitation in India are vital for impact-orientated forecasting, and an essential requirement for mitigating the impact of damaging flood events. Operational forecasts from non-convection-permitting models can have large biases in the intensities of heavy precipitation, and while convection-permitting models can perform better, their operational use over large areas is not yet feasible. Statistical postprocessing can reduce these biases for relatively little computational cost, but few studies have focused on postprocessing forecasts of monsoonal rainfall.We present a postprocessing method for operational precipitation forecasts based on local precipitation distributions for 30 Indian weather types. It is applied to ensemble forecasts for daily precipitation with 12km spatial resolution and lead times of up to 10 days from the Indian National Centre for Medium Range Weather Forecasting (NCMRWF) Ensemble Prediction System (NEPS). The method yields local probabilistic forecasts that are the weighted mean of the observed local precipitation distributions for each weather type, with weights given by the relative frequency of the weather types in the forecast ensemble.The general forecast skill is determined through the Continuous Ranked Probability Skill Score (CRPSS) and the skill for predicting the exceedance of the local 90th percentile is quantified through the Brier Skill Score (BSS). The CRPSS shows moderate improvement over most of India for forecasts with one day lead time, and substantial improvements almost everywhere for longer lead times. The BSS for one day forecasts indicates a spatially complex pattern of higher and lower performance, while for longer lead times the forecasts for heavy precipitation are improved almost everywhere. The improvements with respect to both measures are particularly high over mountainous or wet regions. We will also present reliability diagrams for the raw and postprocessed forecasts of threshold exceedances.

Accurate prediction of the frontal position and intensity of the Loop Current and associated Loop Current Eddies (LC/LCEs) in the Gulf of Mexico (GoM) is notoriously difficult, adversely impacting offshore planning and workability. Here, we review operational forecasting practices and propose a new, unifying, approach for the holistic analysis of oceanographic data, exploring the potential for establishing a new general-purpose set of GoM regimes for the objective classification of its ‘state’ into 1 of 40 discrete regime definitions, as generated through clustering of sea surface height fields obtained from reanalysis data for the period from 1994 to 2015. Drawing inspiration from present methods for the prediction of anticipated LC/LCE impacts, the approach delivers an automatic identification tool to complement operational decision-making, leveraging over 20 years of potential historical analogues to inform impact assessment. Furthermore, it is readily applicable to observational (e.g. satellite) and modelling (e.g. analysis/forecast) fields alike – making expansion to other equivalent spatial datasets simple – and capable of both simplifying the interpretation of dynamical forecasts and seeding the generation of statistical forecasts; opening the potential for a combined, hybrid, approach comprising multiple complementary data sources to be derived in the future. Although still at an early stage of refinement, this is deemed to be a highly important original contribution for operators seeking to improve the efficiency of their planning workflow when forecasting workability in the region.

When local extreme water levels surpass defences, the consequences can be devastating. We assess the importance of sea-level rise and future weather pattern changes on UK coastal flood impacts. Historical weather pattern classifications are matched with the observed skew surges and significant wave heights. Coastal-risk weather patterns are then defined as ≥ 1% of events in the distribution exceeding the local warning threshold. We combine this methodology with projections of sea-level rise and weather pattern frequency occurrences, to determine the relative importance of each on future coastal risk. A deep low-pressure system situated to the west of Ireland (WP29) has the highest probability (6.3%) of exceeding Newlyn’s present-day warning threshold; this is projected to increase under climate change to 46.2% by 2050 under RCP2.6. This work found that weather patterns associated with storm surges are increasing and decreasing in frequency; a synoptic situation causing windy conditions in the north of the UK (WP23) will increase by > 40% under RCP8.5 by the end of the century (2079–2090). When combining the impact of sea-level rise and changing frequency of weather patterns, this study found that sea-level rise dominates future coastal risk and is highly linked to the future emission scenarios. The need for successful adaptation, such as coastal defence improvements and early warning systems, will become even more important under the higher emission pathway. The most significant increases in coastal risk are found along the east coast, through the English Channel to the north Devon coastline.

The clinical diagnostic evaluation of optic neuropathies relies on the analysis of the thickness of the retinal nerve fibre layer (RNFL) by optical coherence tomography (OCT). However, false positives and false negatives in the detection of RNFL abnormalities are common. Here we show that an algorithm integrating measurements of RNFL thickness and reflectance from standard wide-field OCT scans can be used to uncover the trajectories and optical texture of individual axonal fibre bundles in the retina and to discern distinctive patterns of loss of axonal fibre bundles in glaucoma, compressive optic neuropathy, optic neuritis and non-arteritic anterior ischaemic optic neuropathy. Such optical texture analysis can detect focal RNFL defects in early optic neuropathy, as well as residual axonal fibre bundles in end-stage optic neuropathy that were indiscernible by conventional OCT analysis and by red-free RNFL photography. In a diagnostic-performance study, optical texture analysis of the RNFL outperformed conventional OCT in the detection of glaucoma, as defined by visual-field testing or red-free photography. Our findings show that optical texture analysis of the RNFL for the detection of optic neuropathies is highly sensitive and specific.

Supplemental material, sj-pdf-1-jpp-10.1177_08971900211064155 for Impact of Pharmacist-Driven Transitions of Care Interventions on Post-hospital Outcomes Among Patients With Coronary Artery Disease: A Systematic Review by Erin Weeda, Rachael E. Gilbert, Shelby J. Kolo, Jason S. Haney, Linh Tran Hazard, David J. Taber and R. Neal Axon in Journal of Pharmacy Practice

Background: Transitions of care (ToC) aim to provide continuity while preventing loss of information that may result in poor outcomes such as hospital readmission. Readmissions not only burden patients, they also increase costs. Given the high prevalence of coronary artery diseases (CAD) in the United States (US), patients with CAD often make up a significant portion of hospital readmissions. Objective: To conduct a systematic review evaluating the impact of pharmacist-driven ToC interventions on post-hospital outcomes for patients with CAD. Methods: MEDLINE, Scopus, and CINAHL were searched from database inception through 03/2020 using key words for CAD and pharmacists. Studies were included if they: (1) identified adults with CAD at US hospitals, (2) evaluated pharmacist-driven ToC interventions, and (3) assessed post-discharge outcomes. Outcomes were summarized qualitatively. Results: Of the 1612 citations identified, 11 met criteria for inclusion. Pharmacist-driven ToC interventions were multifaceted and frequently included medication reconciliation, medication counseling, post-discharge follow-up and initiatives to improve medication adherence. Hospital readmission and emergency room visits were numerically lower among patients receiving vs not receiving pharmacist-driven interventions, with statistically significant differences observed in 1 study. Secondary prevention measures and adherence tended to be more favorable in the pharmacist-driven intervention groups. Conclusion: Eleven studies of multifaceted, ToC interventions led by pharmacists were identified. Readmissions were numerically lower and secondary prevention measures and adherence were more favorable among patients receiving pharmacist-driven interventions. However, sufficiently powered studies are still required to confirm these benefits.

For those involved in planning for regional and local scale changes in future climate, there is a requirement for climate information to be available in a context more usually associated with meteorological timescales. Here we combine a tool used in numerical weather prediction, the 30 weather patterns produced by the Met Office, which are already applied operationally to numerical weather prediction models, to assess changes in the UK Climate Projections (UKCP) Global ensemble. Through assessing projected changes in the frequency of the weather patterns at the end of the 21st Century, we determine that future changes in large-scale circulation tend towards an increase in winter of weather patterns associated with cyclonic and westerly wind conditions at the expense of more anticyclonic, settled/blocked weather patterns. In summer, the results indicate a shift towards an increase in dry settled weather types with a corresponding reduction in the wet and windy weather types. Climatologically this suggests a shift towards warmer, wetter winters and warmer, drier summers; which is consistent with the headline findings from the UK Climate Projections 2018. This paper represents the first evaluation of weather patterns analysis within UKCP Global. It provides a detailed assessment of the changes in these weather patterns through the 21st Century and how uncertainty in emissions, structural and perturbed parameters affects these results. We show that the use of these weather patterns in tandem with the UKCP projections is useful for future work investigating changes in a range of weather-related climate features such as extreme precipitation.

Veterans suffer disproportionate health impacts from the opioid epidemic, including overdose, suicide, and death. Prediction models based on electronic medical record data can be powerful tools for identifying patients at greatest risk of such outcomes. The Veterans Health Administration implemented the Stratification Tool for Opioid Risk Mitigation (STORM) in 2018. In this study we propose changes to the original STORM model and propose alternative models that improve risk prediction performance. The best of these proposed models uses a multivariate generalized linear mixed modeling (mGLMM) approach to produce separate predictions for overdose and suicide-related events (SRE) rather than a single prediction for combined outcomes. Further improvements include incorporation of additional data sources and new predictor variables in a longitudinal setting. Compared to a modified version of the STORM model with the same outcome, predictor and interaction terms, our proposed model has a significantly better prediction performance in terms of AUC (84% vs. 77%) and sensitivity (71% vs. 66%). The mGLMM performed particularly well in identifying patients at risk for SREs, where 72% of actual events were accurately predicted among patients with the 100,000 highest risk scores compared with 49.7% for the modified STORM model. The mGLMM’s strong performance in identifying true cases (sensitivity) among this highest risk group was the most important improvement given the model’s primary purpose for accurately identifying patients at most risk for adverse outcomes such that they are prioritized to receive risk mitigation interventions. Some predictors in the proposed model have markedly different associations with overdose and suicide risks, which will allow clinicians to better target interventions to the most relevant risks. Supplementary Information The online version contains supplementary material available at 10.1007/s10742-021-00263-7.

The paper opens with a brief overview of the reasons behind the decline of the Breton language in the mid-19th to early 20th Centuries in order to contextualise on-going revitalisation efforts that began in earnest in the 1980s. The discussion then turns to a theoretical review of the literature concerning the key role that translation has been shown to play within the framework of language planning for minority languages within the complementary fields of Polysystems Theory and the Sociology of Translation, arguing that the related yet considerably under-researched field of interpreting can also make a significant contribution to language planning and revitalisation by heightening visibility and symbolic prestige. Finally, the paper presents the results of a limited yet revelatory survey of the main interpreters active in the field in order to shed light on key aspects of the current state of the emerging phenomenon of Breton language interpreting (including interpreter profiles, training, directionality, modalities, voluntary vs. paid work, the clientele, etc.) and their implications with a view to gauging its potential impact for language planning and possible directions for the future.

To conduct a quality improvement evaluation of the Empower Veterans Program (EVP), an interdisciplinary pain rehabilitation/functional restoration program option for functional restoration for high-impact chronic pain, offered in a large metro-area Veterans Health Administration (VHA) system.VHA Corporate Data Warehouse electronic medical record data for patients treated by EVP between 2015 and 2019.This retrospective design first compared EVP patients considered engaged or not engaged in completing treatment in terms of demographic characteristics and post-treatment changes in clinical measures related to opioid use and mental health. We then compared mortality risk between matched groups of treated and untreated patients with chronic pain and concurrent opioid prescriptions using propensity score matching and Cox proportional hazards methods. "Treated" in the matched groups was defined as any level of EVP participation (i.e., both engaged and not engaged).We first identified 1053 EVP patients with 1 year of pre-and post-treatment follow-time and determined their engagement level. From those with chronic pain and prescription opioids, we matched 237 EVP patients to 375 untreated patients.Engaged patients (57.4% of treated patients), were somewhat older than the non-engaged (mean age 57.1 vs. 53.7, Cohen's D = 0.30), and achieved lower mean PHQ9 depression scores in the post-treatment year (9.2 vs. 10.6, Cohen's D = 0.20). Participation in EVP was associated with a 65% lower mortality risk among Veterans with chronic pain and opioid use when compared to the untreated patients: (HR: 0.35, 95% CI: 0.17, 0.75).EVP was associated with a large reduction in mortality risk for Veterans with both chronic pain and opioid use. This result could inform the decision process in a VA station or region when considering providing or expanding access to an interdisciplinary rehabilitation/functional restoration program for chronic pain.

EnglishAfter presenting the key role played by translation in strengthening the literary canon of minoritized languages, this paper goes on to provide a detailed overview and analysis of the past twenty years of Breton literary translation since the turn of the millennium, covering a variety of aspects ranging from the overall evolution over time, target publics, the genres and the authors selected for translation, the range of source languages and the translators themselves, integrating a gender-based outlook whenever necessary. Taken as an integral part of the publishing sector, comparisons are drawn throughout regarding originals published in Breton for the same period. Particular emphasis is also laid on gauging the initial of the Literary Translation Program as a means of determining and potentially redirecting the overall strategy for literary translation going forwards galegoTras exponer a importancia da traducion no proceso de consolidacion do canon literario das linguas minorizadas, este traballo analiza e resume de xeito pormenorizado os ultimos vinte anos de traducions literarias cara ao breton –dende o comezo do milenio– e abrangue diferentes aspectos: a evolucion xeral ao longo do tempo, o publico obxectivo, os xeneros e as autoras/es seleccionados para traducir, a variedade de linguas de partida e as tradutoras/ es per se, incorporando a perspectiva de xenero cando for preciso. Como e unha parte fundamental do sector editorial, tamen se inclue unha comparativacoas obras orixinais publicadas en breton durante o mesmo periodo. Prestouse especial atencion a avaliar a iniciativa do Programa de Traducions Literarias como un xeito de determinar e reorientar, potencialmente, a estratexia global para a traducion literaria de aqui en diante

After presenting the key role played by translation in strengthening the literary canon of minoritized languages, this paper goes on to provide a detailed overview and analysis of the past twenty years of Breton literary translation since the turn of the millennium, covering a variety of aspects ranging from the overall evolution over time, target publics, the genres and the authors selected for translation, the range of source languages and the translators themselves, integrating a gender-based outlook whenever necessary. Taken as an integral part of the publishing sector, comparisons are drawn throughout regarding originals published in Breton for the same period. Particular emphasis is also laid on gauging the initial of the Literary Translation Program as a means of determining and potentially redirecting theoverall strategy for literary translation going forwards.

Introduction: Pulsed Electric Field (PEF) therapy is a novel approach to treat cancer by providing focal tumor ablation while sparing sensitive structures within the tumor micro-environment. Previous studies have demonstrated that PEF induces immunogenic cell death by activating inflammatory signaling pathways and stimulation of antigen presenting cells withing the tumor micro-environment. PEF ablation provides a tumor focused in situ vaccination strategy that combines with checkpoint blockade. We hypothesized that PEF ablation should synergize with chemotherapy and anti-PD1 in a model where checkpoint inhibitors are inactive. Experimental Design: To test this hypothesis, we utilized a highly aggressive syngeneic orthotopic triple negative breast cancer 4T1 mouse model that is non-responsive to anti-PD1 and only marginally responsive to cisplatin to determine if this combination treatment could prolong survival. Thirty-two Balb/c mice were inoculated in the mammary fat pad with 200,000 4T1 cells. Once tumors were established (5mm in diameter), animals were randomized to the following groups: (A) Sham/IgG control (n=8; needle inserted but no PEF), (B) PEF only (n=8), (C) cisplatin + anti-PD-1 (n=8) and (D) PEF + cisplatin + anti PD-1 (n=8). Tumors in groups B and D were treated once with PEF. Anti-PD1 and isotype matched control IgG was administered once per week (200μg, i.p injections) starting on the day of PEF (Group D) for four weeks. Cisplatin was administered (2mg/kg, i.v) once per week for four weeks starting on the day of PEF (d=0) for four weeks. All the mammary fat pad tumors were resected when they achieved a tumor volume of ~200 mm3 to recapitulate post-resection metastatic relapse (See Schematic 1). Results and Conclusions: All mice in the Sham-control IgG group needed to be euthanized by day 43 due to metastases in multiple organs including lungs, bones, liver and brain. All mice in the cisplatin + anti PD-1 group had to be euthanized by day 74. Interestingly, all groups that were treated with PEF survived much longer. On day 90, 28% of mice in the PEF alone group were alive and 43% were alive in the PEF + anti-PD1 + Cisplatin (see Figure 1). The rank-log p-value for the Kaplan-Meier survival curve was statistically significant. In conclusion, our results demonstrate that PEF treatment in combination with anti-PD1 and Cisplatin significantly prolongs survival in a highly aggressive triple negative breast tumor mouse model that is non-responsive to immunotherapy. These findings support evaluation of PEF in cancer patients that are receiving combination of checkpoint blockade and chemotherapy. Citation Format: Chiara Pastori, Mukta Wagh, Ebtesam Nafie, Fatima Murad, Mohit Trikha, Robert Neal. Combination of pulsed electric field, immunotherapy and cisplatin significantly prolongs survival in an orthotopic breast cancer mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6392.

It is easy to look back at a past forecast and assess how well it performed relative to the observed weather, but it is an obvious fact that such verification is only possible after the event has passed. Despite advances in skill in predicting variables such as wind speed or significant wave height, a perennial problem for offshore industry users interested in the incisive application of metocean forecast information to effectively enhance their operational decision-making is knowing how much ‘trust’ to place in these data at lead times beyond a few days ahead. Here, for the first time, we propose a method for the stratification of (past) verification statistics that applies unused information from the (future) forecast to anticipate how well the numerical weather prediction will perform a priori, providing a ‘weather-aware’ estimate of its skill (confidence) before the event has occurred. Stratification is a method for being able to identify differences in characteristics of a particular subset of data, rather than just considering the whole population together. Since forecast performance is partly determined by the ‘drivers of predictability’ at that particular forecast horizon (e.g. prevailing atmosphere/ocean regime), we apply stratification on the basis of the classification of the large-scale weather present at the time to ‘filter’ past verification statistics, as considered in terms of the continuous ranked probability skill score. When used in real-time with a future forecast, the technique offers a refined estimate of the skill by taking advantage of the context of the weather being predicted. The translation of this ‘anticipated verification’ information into a qualitative description offers a robust indicator of confidence, suitable for (dynamically) guiding user trust in the forecast. Using 2.75 years of archived forecast data from the European Centre for Medium-Range Weather Forecasts (ECMWF) extended-range (monthly lead time) ensemble prediction system (EPS) for an example location in the North Sea, the derivation of a dynamic (conditionally sampled) ‘trust index’ is presented; the application of which being evaluated using trials on unseen data from the same site. The benefit of the approach demonstrates significant potential for improving confidence in decision-making from individual short- to medium- range forecasts, as well as building trust in longer-range forecasts. While not a substitute for meteorologist guidance regarding the comprehensiveness of the various drivers of predictability at sub-seasonal timescales, this is none-the-less an important step in making such forecasts usable, useful and used.