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Inflammatory bowel diseases are medically intractable and require constant therapy in many cases. While a growing number of biologicals and small molecules is available for treatment, a substantial portion of patients experiences primary non-response to these compounds and head-to-head evidence for therapy selection is scarce. Thus, approaches to predict treatment success in individual patients are a huge unmet need. We had previously suggested that the expression and function of α4β7 integrin on T cells in the peripheral blood correlate to outcomes of therapy with the anti-α4β7 integrin antibody vedolizumab. Here, we conducted a translational multicenter trial to prospectively evaluate this hypothesis. In a cohort of 89 patients with inflammatory bowel disease undergoing regular therapy with vedolizumab, lower baseline expression of α4β7 was associated with short-term clinical response. Consistently, low α4β7 expression in patients achieving remission predicted sustained remission in week 30. Moreover, high dynamic adhesion of CD4

BACKGROUND Freely-available, asynchronous implementation supports can reduce the resource burden of evidence-based practice (EBP) training to facilitate uptake. Freely-available web-based training videos have proliferated, yet there have been no efforts to quantify their breadth, depth, and content for suicide prevention. OBJECTIVE This study presents results from a scoping review of freely-available training videos for suicide prevention EBPs and describes a methodological framework for reviewing such videos. METHODS A scoping review of freely-available training videos (≥ 2 minutes) for suicide prevention EBPs was conducted using four large video-sharing platforms: YouTube, Vimeo, Bing Video, and Google Video. Identified videos for suicide prevention (N=506) were reviewed and coded. RESULTS Most content was targeted toward gatekeepers (n = 370) versus clinical providers (n = 136). Videos most commonly provided content related to suicidal ideation and/or behaviors (n = 420). A majority of videos (54.2%) included content targeted specifically to certain communities or organizations. Only about half (45.7%) of trainings included formal clinical content pertaining to assessment or intervention for suicide prevention. CONCLUSIONS Results suggested gaps where additional production of freely-available resources is needed. A limited portion of videos provided content aimed at clinical providers delivering formal evidence-based assessments and/or interventions for suicide prevention. Development of resources to address identified gaps may be needed. Future work may leverage machine learning techniques to expedite the review process.

Marine heatwaves (MHWs)—periods of exceptionally warm ocean temperature lasting weeks to years—are now widely recognized for their capacity to disrupt marine ecosystems1–3. The substantial ecological and socioeconomic impacts of these extreme events present significant challenges to marine resource managers4–7, who would benefit from forewarning of MHWs to facilitate proactive decision-making8–11. However, despite extensive research into the physical drivers of MHWs11,12, there has been no comprehensive global assessment of our ability to predict these events. Here we use a large multimodel ensemble of global climate forecasts13,14 to develop and assess MHW forecasts that cover the world’s oceans with lead times of up to a year. Using 30 years of retrospective forecasts, we show that the onset, intensity and duration of MHWs are often predictable, with skilful forecasts possible from 1 to 12 months in advance depending on region, season and the state of large-scale climate modes, such as the El Niño/Southern Oscillation. We discuss considerations for setting decision thresholds based on the probability that a MHW will occur, empowering stakeholders to take appropriate actions based on their risk profile. These results highlight the potential for operational MHW forecasts, analogous to forecasts of extreme weather phenomena, to promote climate resilience in global marine ecosystems.

ObjectiveThe anti-α4β7 integrin antibody vedolizumab is administered at a fixed dose for the treatment of IBDs. This leads to a wide range of serum concentrations in patients and previous studies had suggested that highest exposure levels are associated with suboptimal clinical response. We aimed to determine the mechanisms underlying these non-linear exposure-efficacy characteristics of vedolizumab.DesignWe characterised over 500 samples from more than 300 subjects. We studied the binding of vedolizumab to T cells and investigated the functional consequences for dynamic adhesion, transmigration, gut homing and free binding sites in vivo. Employing single-cell RNA sequencing, we characterised α4β7 integrin-expressing T cell populations ‘resistant’ to vedolizumab and validated our findings in vitro and in samples from vedolizumab-treated patients with IBD. We also correlated our findings with a post-hoc analysis of the Gemini II and III studies.ResultsRegulatory T (TReg) cells exhibited a right-shifted vedolizumab binding profile compared with effector T (TEff) cells. Consistently, in a certain concentration range, the residual adhesion, transmigration, homing of and availability of functional α4β7 on TReg cells in vivo was higher than that of/on TEff cells. We identified a vedolizumab-‘resistant’ α4β7-expressing β1+PI16+ TReg cell subset with pronounced regulatory properties as the substrate for this effect. Our observations correlated with exposure-efficacy data from Gemini II and III trials.ConclusionCompletely blocking TEff cell trafficking with vedolizumab, while simultaneously permitting residual homing of powerful TReg cells in an optimal ‘therapeutic window’ based on target exposure levels might be a strategy to optimise treatment outcomes in patients with IBD.

This dataset is a supplement to the paper: 'A hybrid dynamical approach for seasonal prediction of sea-level anomalies: a pilot study for Charleston, South Carolina'. Please cite this paper when using this dataset. (c) 2022 All rights reserved. This dataset can be used in combination with the scripts that are provided in a Github repository. Contents adjoint_sensitivities.zip: Contains the adjoint sensitivities of sea level in Charleston to wind stress, heat, and freshwater fluxes, as described in the paper. These files are in binary format. Some scripts to read these files and sort them accordingly can be found in the aforementioned Github repository. An example can be found in 'convert_sens_to_2d.jl'. results_tseries.zip: Contains the time series of observed, reconstructed, and predicted sea level. Provided are the estimates for tide-gauge (TG) and altimetry (Alt) observations, both detrended and non-detrended. The data are stored in the NetCDF format. results_stats.zip: Contains the statistics of all reconstructions and projections. Similar to the time series files, the estimates are provided for benchmarks against altimetry (Alt) and tide-gauge (TG) observations, both detrended and non-detrended. These data are also stored in NetCDF format. &nbsp

The relationship between the Warm Water Volume (WWV) ENSO precursor and ENSO SST weakened substantially after ~2000, coinciding with a degradation in dynamical model ENSO prediction skill. It is important to understand the drivers of the equatorial thermocline temperature variations and their linkage to ENSO onsets. In this study, a set of ocean reanalyses is employed to assess factors responsible for the variation of the equatorial Pacific Ocean thermocline during 1982-2019. Off-equatorial thermocline temperature anomalies carried equatorward by the mean meridional currents associated with Pacific Tropical Cells are shown to play an important role in modulating the central equatorial thermocline variations, which is rarely discussed in the literature. Further, ENSO events are delineated into two groups based on precursor mechanisms: the western equatorial type (WEP) ENSO, when the central equatorial thermocline is mainly influenced by the zonal propagation of anomalies from the western Pacific, and the off-equatorial central Pacific (OCP) ENSO, when off-equatorial central thermocline anomalies play the primary role. WWV is found to precede all WEP ENSO by 6-9 months, while the correlation is substantially lower for OCP ENSO events. In contrast, the central tropical Pacific (CTP) precursor, which includes off-equatorial thermocline signals, has a very robust lead correlation with the OCP ENSO. Most OCP ENSO events are found to follow the same ENSO conditions, and the number of OCP ENSO increases substantially since the 21st century. These results highlight the importance of monitoring off-equatorial subsurface preconditions for ENSO prediction and to understand multi-year ENSO.

The Northern Annular Mode (NAM) dominates variability of the Northern Hemisphere (NH) wintertime extratropical circulation in both the troposphere and stratosphere. Changes in the tropospheric NAM (i.e., changes in the position and strength of the polar jet stream) directly alter NH mid-latitude temperature and precipitation patterns, making forecasting these changes a significant priority for subseasonal-to-seasonal (S2S) forecasts during boreal winter. This study examines fundamental characteristics of the wintertime tropospheric circulation pattern in the hindcast simulations of the North American Multi-Model Ensemble (NMME) Phase-2 model suite through examining how the models capture sudden stratospheric warming (SSW) events, known to precede large changes in the tropospheric NAM by 2–6 weeks. Findings indicate that the NMME Phase-2 models have an overall mixed performance in capturing the characteristics of the NAM and its teleconnections. Biases are apparent in the dominant nodes of the tropospheric NAM pattern, storm tracks and associated wave fluxes in the Atlantic, and a systematic underestimation of intraseasonal variability of the NH stratospheric polar vortex in the models (i.e., the stratospheric NAM). We then investigate the ability of the models to simulate the life cycle of model-identified SSW events, including pre- and post-SSW circulation patterns and sensible weather conditions. Specific model biases include inconsistent geopotential height precursor fields, weaker-than-observed vertical wave propagation prior to SSW events, and incorrect surface temperature regimes following the events. Together, the results suggest potential pathways forward for improving subseasonal winter weather forecasts associated with the NAM using the NMME Phase-2 models.

Congenital syphilis represents an important public health challenge in the United States, and its prevalence has been increasing for the past 10 years because of many factors. The diagnosis can be difficult given its various and nonspecific clinical manifestations in newborns, and the possibility of false negative results during prenatal care. The prozone phenomenon, caused by an excess of antibody, which interferes with the regular screening tests, is a cause of false negative tests. This could delay the diagnosis and increase morbidity and mortality in the newborn. We present a case of congenital syphilis in a 3-month-old infant whose mother had prenatal care and negative tests for syphilis, which contributed to the late diagnosis. In the face of clinical findings suggestive of congenital syphilis and negative maternal syphilis tests healthcare providers should consider the possibility of maternal false negative test caused by the prozone phenomenon.

There is high demand and a growing expectation for predictions of environmental conditions that go beyond 0–14-day weather forecasts with outlooks extending to one or more seasons and beyond. This is driven by the needs of the energy, water management, and agriculture sectors, to name a few. There is an increasing realization that, unlike weather forecasts, prediction skill on longer time scales can leverage specific climate phenomena or conditions for a predictable signal above the weather noise. Currently, it is understood that these conditions are intermittent in time and have spatially heterogeneous impacts on skill, hence providing strategic windows of opportunity for skillful forecasts. Research points to such windows of opportunity, including El Niño or La Niña events, active periods of the Madden–Julian oscillation, disruptions of the stratospheric polar vortex, when certain large-scale atmospheric regimes are in place, or when persistent anomalies occur in the ocean or land surface. Gains could be obtained by increasingly developing prediction tools and metrics that strategically target these specific windows of opportunity. Across the globe, reevaluating forecasts in this manner could find value in forecasts previously discarded as not skillful. Users’ expectations for prediction skill could be more adequately met, as they are better aware of when and where to expect skill and if the prediction is actionable. Given that there is still untapped potential, in terms of process understanding and prediction methodologies, it is safe to expect that in the future forecast opportunities will expand. Process research and the development of innovative methodologies will aid such progress.

Several mechanisms originating in the Northern (NH) and Southern Hemisphere (SH) are argued to have the ability to stochastically force ENSO events. In this study, the impact of these extratropical mechanisms on ENSO diversity and predictability are evaluated using linear regression methodologies from information theory and machine learning applied to observational data. Overfitting is often an issue when investigating different extratropical mechanisms, as they are highly correlated in both space and time. The statistical methods in this study are specifically designed to address this issue. Results show that at 1-year lead-times, the extratropics are related to development of Central Pacific (CP), but not Eastern Pacific (EP) ENSO events. In boreal winter, the SH extratropics contribute to the predictability of CP ENSO, much further in advance than previous studies have indicated. The dominant NH predictor of CP ENSO from one winter to the next is identified as a sea surface temperature dipole in the Western North Pacific. Finally, separation of CP ENSO into its extratropical and tropical related components demonstrates that CP ENSO events with strong forcing from the extratropics start one season earlier than events primarily forced from the Tropics and thus have the potential for longer lead predictability, up to 1-year in advance of a CP ENSO event.

Background Blocking immune cell gut homing via α4β7 integrin with the monoclonal antibody vedolizumab is an established therapeutic strategy in inflammatory bowel disease. However, despite promising preclinical and phase 2 clinical data, the anti-β7 antibody etrolizumab yielded disappointing results in a large phase 3 trial program in UC. Mechanistic explanations are still lacking. We have recently shown that vedolizumab is associated with residual homing of regulatory T (Treg) cells in a certain exposure range and aimed to investigate whether a similar mechanism applies for etrolizumab. Methods We used flow cytometry, competitive dynamic adhesion, and transmigration assays to assess binding of the etrolizumab surrogate (etrolizumab-s) antibody FIB504 to Treg and effector T cells (Teff) and to explore the impact on cell trafficking. Results We observed only minimal differences in the binding of etrolizumab-s to Treg and Teff cells. Dynamic adhesion and transmigration of Treg and Teff cells was not substantially differentially affected at relevant concentrations. The β1+ and PI16+ Treg cells were only resistant to etrolizumab-s at low concentrations. Conclusions Etrolizumab does not seem to induce notable residual trafficking of Treg cells. Thus, the Teff overweight in the inflamed gut might persist despite reduced overall T cell recruitment. This might be one piece of the puzzle to explain recent clinical results in phase 3.

BackgroundParticipatory design methods are a key component of designing tailored implementation strategies. These methods vary in the resources required to execute and analyze their outputs. No work to date has examined the extent to which the output obtained from different approaches to participatory design varies.MethodsWe concurrently used two separate participatory design methods: 1) field observations and qualitative interviews and 2) rapid crowd sourcing (an innovation tournament). Our goal was to generate information to tailor implementation strategies to increase the use of evidence-based data collection practices among one-to-one aides working with children with autism. Each method was executed and analyzed by study team members blinded to the output of the other method. We estimated the personnel time and monetary costs associated with each method to further facilitate comparison.ResultsObservations and interviews generated nearly double the number of implementation strategies (n = 26) than did the innovation tournament (n = 14). When strategies were classified into clusters from the Expert Recommendations for Implementing Change (ERIC) taxonomy, there was considerable overlap in the content of identified strategies. Strategies derived from observations and interviews were more specific than those from the innovation tournament. Nine strategies (23%) reflected content unique to observations and interviews and 4 (10%) strategies were unique to the innovation tournament. Only observations and interviews identified implementation strategies related to adapting and tailoring to context; only the innovation tournament identified implementation strategies that used incentives. Observations and interviews required more than three times the personnel hours than the innovation tournament, but the innovation tournament was more costly overall due to the technological platform used.ConclusionsThere was substantial overlap in content derived from observations and interviews and the innovation tournament. However, each yielded unique information. To select the best participatory design approach to inform implementation strategy design for a particular context, researchers should carefully consider what each method may elicit and weigh the resources available to invest in the process.Trial RegistrationN/A

Marine heatwaves (MHWs)-periods of exceptionally warm ocean temperature lasting weeks to years-are now widely recognized for their capacity to disrupt marine ecosystems

A profound westward shift in atmosphere–ocean variability in the tropical Pacific is observed when 2000–2017 is compared to 1979–1999. This westward displacement is associated with changes in oceanic Kelvin wave activity along the equator, especially a remarkable reduction in the eastern Pacific (175°–145°W). This coincides with a weakening of low-level westerly winds in this region, and a westward shift of low-level easterly winds in the central and eastern tropical Pacific, as well as decreased variability of vertical entrainment, vertical diffusion in the ocean mixed-layer in the eastern Pacific. The observed enhancement of the zonal contrast of the mean state across the tropical Pacific seems to be associated with the westward shift of climate variability along the equator. This systematically westward shift of the atmosphere–ocean variability in the tropical Pacific alters the impact of the tropical Pacific on extra-tropical climate.

Recent research demonstrates that dynamical models sometimes fail to represent observed teleconnection patterns associated with predictable modes of climate variability. As a result, model forecast skill may be reduced. We address this gap in skill through the application of a Bayesian postprocessing technique—the calibration, bridging, and merging (CBaM) method—which previously has been shown to improve probabilistic seasonal forecast skill over Australia. Calibration models developed from dynamical model reforecasts and observations are employed to statistically correct dynamical model forecasts. Bridging models use dynamical model forecasts of relevant climate modes (e.g., ENSO) as predictors of remote temperature and precipitation. Bridging and calibration models are first developed separately using Bayesian joint probability modeling and then merged using Bayesian model averaging to yield an optimal forecast. We apply CBaM to seasonal forecasts of North American 2-m temperature and precipitation from the North American Multimodel Ensemble (NMME) hindcast. Bridging is done using the model-predicted Niño-3.4 index. Overall, the fully merged CBaM forecasts achieve higher Brier skill scores and better reliability compared to raw NMME forecasts. Bridging enhances forecast skill for individual NMME member model forecasts of temperature, but does not result in significant improvements in precipitation forecast skill, possibly because the models of the NMME better represent the ENSO–precipitation teleconnection pattern compared to the ENSO–temperature pattern. These results demonstrate the potential utility of the CBaM method to improve seasonal forecast skill over North America.

Three strategies for creating probabilistic forecast outlooks for El Niño–Southern Oscillation (ENSO) are compared. One is subjective and is currently used by the NOAA/Climate Prediction Center (CPC) to produce official ENSO outlooks. A second is purely objective and is based on the North American Multimodel Ensemble (NMME). A new third strategy is proposed in which the forecaster only provides the expected value of the Niño-3.4 index, and then categorical probabilities are objectively determined based on past skill. The new strategy results in more confident probabilities compared to the subjective approach and higher verification scores, while avoiding the significant forecast busts that sometimes afflict the NMME-based objective approach. The higher verification scores of the new strategy appear to result from the added value that forecasters provide in predicting the mean, combined with more reliable representations of uncertainty, which is difficult to represent because forecasters often assume less confidence than is justified. Moreover, the new approach can produce higher-resolution probabilistic forecasts that include ENSO strength information and that are difficult, if not impossible, for forecasters to produce. To illustrate, a nine-category ENSO outlook based on the new strategy is assessed and found to be skillful. The new approach can be applied to other outlooks where users desire higher-resolution probabilistic forecasts, including the extremes.

The anti-α4β7 integrin antibody vedolizumab is administered at a fixed dose for the treatment of IBDs. This leads to a wide range of serum concentrations in patients and previous studies had suggested that highest exposure levels are associated with suboptimal clinical response. We aimed to determine the mechanisms underlying these non-linear exposure-efficacy characteristics of vedolizumab.We characterised over 500 samples from more than 300 subjects. We studied the binding of vedolizumab to T cells and investigated the functional consequences for dynamic adhesion, transmigration, gut homing and free binding sites in vivo. Employing single-cell RNA sequencing, we characterised α4β7 integrin-expressing T cell populations 'resistant' to vedolizumab and validated our findings in vitro and in samples from vedolizumab-treated patients with IBD. We also correlated our findings with a post-hoc analysis of the Gemini II and III studies.Regulatory T (TCompletely blocking T

One of the emerging topics in climate prediction is the issue of the so-called “signal-to-noise paradox”, characterized by too small signal-to-noise ratio in current model predictions that cannot reproduce the realistic signal. Recent studies have suggested that seasonal-to-decadal climate can be more predictable than ever expected due to the paradox. But no studies, to the best of our knowledge, have been focused on whether the signal-to-noise paradox exists in subseasonal predictions. The present study seeks to address the existence of the paradox in subseasonal predictions based on (i) coupled model simulations participating in phase 5 and phase 6 of the Coupled Model Intercomparison Project (CMIP5 and CMIP6, respectively), and (ii) subseasonal hindcast outputs from the Subseasonal Experiment (SubX) and the Subseasonal-to-Seasonal Prediction (S2S) projects. Of particular interest is the possible existence of the paradox in the new generation of GFDL SPEAR model, through the diagnosis of which may help identify potential issues in the new forecast system to guide future model development and initialization. Here we investigate the paradox issue using two methods: the ratio of predictable component defined as the ratio of predictable component in the real world to the signal-to-noise ratio in models and the persistence/dispersion characteristics estimated from a Markov model framework. The preliminary results suggest a potentially widespread occurrence of the signal-to-noise paradox in subseasonal predictions, further implying some room for improvement in future ensemble-based subseasonal predictions.

When will a particular city on the Eastern Seaboard have a 70% chance of flooding at least one hour on at least 70 days of the year? This jam-packed question drives this study, as coastal flooding ...

OBJECTIVES: The anti-α4β7 integrin antibody vedolizumab (VDZ) is successfully used for the treatment of inflammatory bowel diseases. However, only a subgroup of patients respond to therapy. VDZ is administered at a fixed dose, leading to a wide range of serum concentrations in patients. Previous work from our group showed a dose-dependent preferential binding of VDZ to effector compared with regulatory CD4+ T cells. Therefore, we aimed to determine the dose-dependent binding profile of VDZ to other leukocyte subsets. METHODS: We characterized α4β7 integrin expression on CD8+ T cells, CD19+ B cells, CD14+ monocytes, natural killer cells, and eosinophils from patients with inflammatory bowel disease and healthy controls. We studied the binding of VDZ to these cells at different concentrations and investigated the functional consequences for dynamic adhesion and transmigration in vitro. RESULTS: The expression of α4β7 differed between the analyzed leukocyte subsets and was significantly higher on eosinophils from inflammatory bowel disease patients compared with controls. Almost all α4β7-expressing cells from these subsets were bound by VDZ at a concentration of 10 μg/mL. Dynamic cell adhesion was significantly impaired in all subsets, but there were no dose-dependent differences in the inhibition of adhesion. DISCUSSION: Our data suggest that α4β7-expressing CD8+ T cells, CD19+ B cells, CD14+ monocytes, natural killer cells, and eosinophils are a target of VDZ. However, there do not seem to be concentration-dependent differences, regarding the effects on these cells in the clinically relevant range. Thus, the reported exposure-efficacy characteristic of VDZ can probably mainly be attributed to CD4+ T-cell subsets.

Background Vedolizumab has become a standard treatment for the inflammatory bowel diseases ulcerative colitis (UC) and Crohn’s disease (CD). However, there is an ongoing debate on the ideal individual treatment algorithms and means to predict treatment response are not routinely established. Aims We aimed to describe our experiences with vedolizumab at a large German tertiary referral center and to identify clinical predictors of success of vedolizumab treatment. Methods We performed a retrospective single-center cohort study employing univariable and multivariable analyses as well as Kaplan–Meier analyses of persistence on treatment. Results 36% and 35% of the patients with UC and CD, respectively, reached clinical remission after 17 weeks. Patients with lower clinical disease activity were more likely to achieve remission. The median persistence on treatment was 33 months for UC and 29 months for CD. Conclusion Our study confirms that vedolizumab is an efficient option for the treatment of UC and CD. Clinical parameters of disease activity may help to predict the success of treatment.

Background and Aims The molecular mechanism of action of the Janus kinase [JAK] inhibitor tofacitinib is poorly understood. Methods Here we analysed the inhibitory effect of tofacitinib on mucosal and blood T cells from patients with ulcerative colitis [UC]. Furthermore, tofacitinib treatment was analysed in experimental colitis models and wound healing. Additionally, tofacitinib effects were analysed in bioassays. Results Tofacitinib significantly reduced T cell-derived inflammatory cytokine production [Th2, Th9, Th17] in patients with active UC. Additionally, impaired expression of the homing receptors alpha4/beta1 and alpha4/beta7, as well as reduced gut homing capacity of T cells in a humanised mouse model of colitis, were observed. Tofacitinib suppressed acute and chronic oxazolone colitis, compared with untreated wild-type mice, associated with downregulation of cytokines produced by Th2, Th9, and Th17 cells. Functionally, tofacitinib induced apoptosis of intestinal epithelial cells and prevented mucosal wound healing in vivo at higher concentration. Thus, our findings suggest that tofacitinib is quite effective in protecting from colitis, by inhibition of a bundle of T cell-derived cytokines like IL-5, IL-6, IL-9, IL-13, and IL-17A. Conclusions Application of tofacitinib emerges as an attractive concept for treatment of chronic intestinal inflammation at lower concentrations, whereas higher concentrations require attention due to prolonged wound healing. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

Weather and climate variations on subseasonal to decadal time scales can have enormous social, economic, and environmental impacts, making skillful predictions on these time scales a valuable tool for decision-makers. As such, there is a growing interest in the scientific, operational, and applications communities in developing forecasts to improve our foreknowledge of extreme events. On subseasonal to seasonal (S2S) time scales, these include high-impact meteorological events such as tropical cyclones, extratropical storms, floods, droughts, and heat and cold waves. On seasonal to decadal (S2D) time scales, while the focus broadly remains similar (e.g., on precipitation, surface and upper-ocean temperatures, and their effects on the probabilities of high-impact meteorological events), understanding the roles of internal variability and externally forced variability such as anthropogenic warming in forecasts also becomes important. The S2S and S2D communities share common scientific and technical challenges. These include forecast initialization and ensemble generation; initialization shock and drift; understanding the onset of model systematic errors; bias correction, calibration, and forecast quality assessment; model resolution; atmosphere-ocean coupling; sources and expectations for predictability; and linking research, operational forecasting, and end-user needs. In September 2018 a coordinated pair of international conferences, framed by the above challenges, was organized jointly by the World Climate Research Programme (WCRP) and the World Weather Research Programme (WWRP). These conferences surveyed the state of S2S and S2D prediction, ongoing research, and future needs, providing an ideal basis for synthesizing current and emerging developments in these areas that promise to enhance future operational services. This article provides such a synthesis. Fil: Merryfield, William J.. Canadian Centre For Climate Modelling And Analysis; Canadá Fil: Baehr, Johanna. Universitat Hamburg; Alemania Fil: Batté, Lauriane. Centre National de Recherches Météorologiques; Francia Fil: Becker, Emily J.. No especifíca; Fil: Butler, Amy H.. State University of Colorado at Boulder; Estados Unidos Fil: Coelho, Caio A.S.. Instituto Nacional de Pesquisas Espaciais; Brasil Fil: Danabasoglu, Gokhan. National Center for Atmospheric Research; Estados Unidos Fil: Dirmeyer, Paul A.. No especifíca; Fil: Doblasreyes, Francisco. No especifíca; Fil: Domeisen, Daniela I.V.. No especifíca; Fil: Ferranti, Laura. No especifíca; Fil: Ilynia, Tatiana. No especifíca; Fil: Kumar, Arun. No especifíca; Fil: Müller, Wolfgang A.. No especifíca; Fil: Rixen, Michel. World Meteorological Organization; Estados Unidos Fil: Robertson, Andrew W.. International Research Institute For Climate And Society; Estados Unidos Fil: Smith, Doug M.. No especifíca; Fil: Takaya, Yuhei. Japan Meteorological Agency; Japón Fil: Tuma, Matthias. World Meteorological Organization; Estados Unidos Fil: Vitart, Frederic. No especifíca; Fil: White, Christopher J.. University of Strathclyde; Reino Unido Fil: Alvarez, Mariano Sebastián. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina Fil: Ardilouze, Constantin. No especifíca; Fil: Attard, Hannah. No especifíca; Fil: Baggett, Cory. State University of Colorado - Fort Collins; Estados Unidos Fil: Balmaseda, Magdalena A.. No especifíca; Fil: Beraki, Asmerom F.. University Of Pretoria; Sudáfrica Fil: Bhattacharjee, Partha S.. National Oceanic And Atmospheric Administration; Estados Unidos Fil: Bilbao, Roberto. Barcelona Supercomputing Center - Centro Nacional de Supercomputacion; España Fil: De Andrade, Felipe M.. University of Reading; Reino Unido Fil: DeFlorio, Michael J.. No especifíca; Fil: Díaz, Leandro Baltasar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina Fil: Ehsan, Muhammad Azhar. The Abdus Salam. International Centre for Theoretical Physics; Italia. The Abdus Salam; Italia Fil: Fragkoulidis, Georgios. Johannes Gutenberg Universitat Mainz; Alemania Fil: Grainger, Sam. No especifíca; Fil: Green, Benjamin W.. State University of Colorado at Boulder; Estados Unidos Fil: Hell, Momme C.. No especifíca; Fil: Infanti, Johnna M.. National Oceanic And Atmospheric Administration; Estados Unidos Fil: Isensee, Katharina. No especifíca; Fil: Kataoka, Takahito. No especifíca; Fil: Kirtman, Ben P.. No especifíca; Fil: Klingaman, Nicholas P.. University of Reading; Reino Unido Fil: Lee, June Yi. Pusan National University; Corea del Sur Fil: Mayer, Kirsten. State University of Colorado at Boulder; Estados Unidos Fil: McKay, Roseanna. Monash University; Australia Fil: Mecking, Jennifer V.. University of Southampton; Reino Unido Fil: Miller, Douglas E.. University of Illinois. Urbana - Champaign; Estados Unidos Fil: Neddermann, Nele. No especifíca; Fil: Ng, Ching Ho Justin. University of Princeton; Estados Unidos Fil: Ossó, Albert. University of Graz; Austria Fil: Pankatz, Klaus. Max Planck Institute For Meteorology; Estados Unidos Fil: Peatman, Simon. No especifíca; Fil: Pegion, Kathy. George Mason University; Estados Unidos Fil: Perlwitz, Judith. State University of Colorado at Boulder; Estados Unidos Fil: Recalde Coronel, G. Cristina. Escuela Superior Politecnica del Litoral ; Ecuador Fil: Reintges, Annika. Geomar-Helmholtz Centre for Ocean Research Kiel; Alemania Fil: Renkl, Christoph. Dalhousie University Halifax; Canadá Fil: Solaraju-Murali, Balakrishnan. Barcelona Supercomputing Center - Centro Nacional de Supercomputacion; España Fil: Spring, Aaron. No especifíca; Fil: Stan, Cristiana. George Mason University; Estados Unidos Fil: Sun, Y. Qiang. University of Princeton; Estados Unidos Fil: Tozer, Carly R.. No especifíca; Fil: Vigaud, Nicolas. No especifíca; Fil: Woolnough, Steven. University of Reading; Reino Unido Fil: Yeager, Stephen. National Center for Atmospheric Research; Estados Unidos

* This essay stems from international conferences on subseasonal to seasonal and seasonal to decadal prediction jointly convened by WWRP and WCRP in September 2018 in Boulder, Colorado: (www.wcrp-climate.org/s2s-s2d-2018-home). Adapted from “Current and Emerging Developments in Subseasonal to Decadal Prediction,”. Published Online in BAMS, June 2020. For the full, citable article, see DOI:10.1175 /BAMS-D-19-0037.1. © Copyright 2020 American Meteorological Society (AMS). For permission to reuse any portion of this Work, please contact permissions@ametsoc.org. Any use of material in this Work that is determined to be “fair use” under Section 107 of the U.S. Copyright Act (17 U.S. Code § 107) or that satisfies the conditions specified in Section 108 of the U.S. Copyright Act (17 USC § 108) does not require the AMS’s permission. Republication, systematic reproduction, posting in electronic form, such as on a website or in a searchable database, or other uses of this material, except as exempted by the above statement, requires written permission or a license from the AMS. All AMS journals and monograph publications are registered with the Copyright Clearance Center (https://www.copyright.com). Additional details are provided in the AMS Copyright Policy statement, available on the AMS website (https://www.ametsoc.org/PUBSCopyrightPolicy). Tremendous recent progress in climate prediction on subseasonal to decadal time scales has been enabled by better observations, data assimilation, and models originating from the weather prediction and climate simulation communities together with ever-increasing computational power. World Climate Research Program (WCRP) efforts led initially to predictions one to two seasons ahead becoming part of the WMO operational infrastructure. More recently, a joint World Weather Research Program (WWRP) and WCRP Subseasonal to Seasonal Prediction Project has started tackling the weather–climate gap (from two weeks to a season). The NOAA-led Subseasonal Experiment project has similar aims. New frontiers have been enabled by Earth system models that represent the carbon and other biogeochemical cycles in addition to the physical climate system. As a result, skillful multiyear prediction is likely achievable for biogeochemical and ecological Earth system components. The ultimate collective subseasonal to seasonal (S2S; 2 weeks to season) and seasonal to decadal (S2D) endeavor is to improve the prediction of the spatial–temporal continuum connecting weather to climate through a coordinated, seamless, and integrated Earth system approach. The S2S and S2D communities share common scientific and technical challenges. This essay* synthesizes those commonalities across time scales and Earth system components, and from basic research to operational delivery. Peer Reviewed Article signat per 65 autors/es: William J. Merryfield, Johanna Baehr, Lauriane Batté, Emily J. Becker, Amy H. Butler, Caio A. S. Coelho, Gokhan Danabasoglu, Paul A. Dirmeyer, Francisco J. Doblas-Reyes, Daniela I. V. Domeisen, Laura Ferranti, Tatiana Ilynia, Arun Kumar, Wolfgang A. Müller, Michel Rixen, Andrew W. Robertson, Doug M. Smith, Yuhei Takaya, Matthias Tuma, Frederic Vitart, Christopher J. White, Mariano S. Alvarez, Constantin Ardilouze, Hannah Attard, Cory Baggett, Magdalena A. Balmaseda, Asmerom F. Beraki, Partha S. Bhattacharjee, Roberto Bilbao, Felipe M. de Andrade, Michael J. DeFlorio, Leandro B. Díaz, Muhammad Azhar Ehsan, Georgios Fragkoulidis, Sam Grainger, Benjamin W. Green, Momme C. Hell, Johnna M. Infanti, Katharina Isensee, Takahito Kataoka, Ben P. Kirtman, Nicholas P. Klingaman, June-Yi Lee, Kirsten Mayer, Roseanna McKay, Jennifer V. Mecking, Douglas E. Miller, Nele Neddermann, Ching Ho Justin Ng, Albert Ossó, Klaus Pankatz, Simon Peatman, Kathy Pegion, Judith Perlwitz, G. Cristina Recalde-Coronel, Annika Reintges, Christoph Renkl, Balakrishnan Solaraju-Murali, Aaron Spring, Cristiana Stan, Y. Qiang Sun, Carly R. Tozer, Nicolas Vigaud, Steven Woolnough, and Stephen Yeager.

ObjectiveTo study the role of α4β7 integrin for gut homing of monocytes and to explore the biological consequences of therapeutic α4β7 inhibition with regard to intestinal wound healing.DesignWe studied the expression of homing markers on monocyte subsets in the peripheral blood and on macrophage subsets in the gut of patients with IBD and controls with flow cytometry and immunohistochemistry. Integrin function was addressed with dynamic adhesion assays and in vivo gut homing assays. In vivo wound healing was studied in mice deficient for or depleted of α4β7 integrin.ResultsClassical and non-classical monocytes were clearly dichotomous regarding homing marker expression including relevant expression of α4β7 integrin on human and mouse non-classical monocytes but not on classical monocytes. Monocyte-expressed α4β7 integrin was functionally important for dynamic adhesion to mucosal vascular addressin cell adhesion molecule 1 and in vivo gut homing. Impaired α4β7-dependent gut homing was associated with reduced (effect size about 20%) and delayed wound healing and suppressed perilesional presence of wound healing macrophages. Non-classical monocytes in the peripheral blood were increased in patients with IBD under clinical treatment with vedolizumab.ConclusionIn addition to reported effects on lymphocytes, anti-α4β7 therapy in IBD also targets non-classical monocytes. Impaired gut homing of such monocytes might lead to a reduction of wound healing macrophages and could potentially explain increased rates of postoperative complications in vedolizumab-treated patients, which have been observed in some studies.

From January through March 2017, a series of extreme precipitation events occurred in coastal Peru, causing severe floods with hundreds of human casualties and billions of dollars in economic losses. The extreme precipitation was a result of unusually strong recurrent patterns of atmospheric and oceanic conditions, including extremely warm coastal sea surface temperatures (SST) and weakened trade winds. These climatic features and their causal relationship with the Peruvian precipitation were examined. Diagnostic analysis and model experiments suggest that an atmospheric forcing in early 2017, which was moderately linked to the Trans-Niño Index (TNI), initiated the local SST warming along coastal Peru that later expanded to the equator. In January 2017, soil moisture was increased by an unusual expansion of Amazonian rainfall. By March, localized and robust SST warming provided positive feedback to the weakening of the trade winds, leading to increased onshore wind and a subsequent enhancement in rainfall. The analysis points to a tendency towards more frequent and stronger variations in the water vapor flux convergence along the equator, which is associated with the increased precipitation in coastal Peru.