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The availability of publicly subsidized rental assistance does not meet demand, making waiting lists a reality for many individuals who apply for assistance. However, information about waitlisted applicants has rarely been collected as a means of understanding the demand for rental assistance in the United States (US). Publicly financed rental assistance provides an important economic resource to nearly 2 million persons aged 65 and older. Because older persons are more likely than younger persons to experience chronic health conditions and disability, it is important to also understand how health influences applicants’ perceived housing needs. The aims of this study were to describe the housing and health characteristics of older adults who applied for rental assistance. A mailed survey was completed by 267 waitlisted applicants aged 55 and older, and 29 of these respondents participated in a qualitative, in-depth interview. Survey results indicate that many applicants have poor health, experienc...

Predictability is an intrinsic limit of the climate system due to uncertainty in initial conditions and the chaotic nature of the atmosphere. Estimates of predictability together with calculations of current prediction skill are used to define the gaps in our prediction capabilities, inform future model developments, and indicate to stakeholders the potential for making forecasts that can inform their decisions. The true predictability of the climate system is not known and must be estimated, typically using a perfect model estimate from an ensemble prediction system. However, different prediction systems can give different estimates of predictability. Can we determine which estimate of predictability is most representative of the true predictability of the climate system? We test three metrics as potential indicators of the fidelity of predictability estimates in an idealized framework—the spread-error relationship, autocorrelation and skill. Using the North American multi-model ensemble re-forecast database, we quantify whether these metrics accurately indicate a model’s ability to properly estimate predictability. It is found that none of these metrics is a robust measure for determining whether a predictability estimate is realistic for El Nino-Southern oscillation events. For temperature and precipitation over land, errors in the spread-error ratio are related to errors in estimating predictability at the shortest lead-times, while skill is not related to predictability errors. The relationship between errors in the autocorrelation and errors in estimating predictability varies by lead-time and region.

The dramatic switch from extreme drought to severe flooding in California, and the accompanying flip from atmospheric ridge to trough in the northeastern Pacific, exemplifies the pathways to an intensified water cycle under a warming climate.

While seasonal outlooks have been operational for many years, until recently the extended-range timescale referred to as subseasonal-to-seasonal (S2S) has received little attention. S2S prediction fills the gap between short-range weather prediction and long-range seasonal outlooks. Decisions in a range of sectors are made in this extended-range lead time; therefore, there is a strong demand for this new generation of forecasts. International efforts are under way to identify key sources of predictability, improve forecast skill and operationalize aspects of S2S forecasts; however, challenges remain in advancing this new frontier. If S2S predictions are to be used effectively, it is important that, along with science advances, an effort is made to develop, communicate and apply these forecasts appropriately. In this study, the emerging operational S2S forecasts are presented to the wider weather and climate applications community by undertaking the first comprehensive review of sectoral applications of S2S predictions, including public health, disaster preparedness, water management, energy and agriculture. The value of applications-relevant S2S predictions is explored, and the opportunities and challenges facing their uptake are highlighted. It is shown how social sciences can be integrated with S2S development, from communication to decision-making and valuation of forecasts, to enhance the benefits of ‘climate services’ approaches for extended-range forecasting. While S2S forecasting is at a relatively early stage of development, it is concluded that it presents a significant new window of opportunity that can be explored for application-ready capabilities that could allow many sectors the opportunity to systematically plan on a new time horizon.

The skill of monthly sea surface temperature (SST) anomaly predictions for large marine ecosystems (LMEs) in coastal regions of the United States and Canada is assessed using simulations from the climate models in the North American Multimodel Ensemble (NMME). The forecasts based on the full ensemble are generally more skillful than predictions from even the best single model. The improvement in skill is particularly noteworthy for probability forecasts that categorize SST anomalies into upper (warm) and lower (cold) terciles. The ensemble provides a better estimate of the full range of forecast values than any individual model, thereby correcting for the systematic over-confidence (under-dispersion) of predictions from an individual model. Probability forecasts, including tercile predictions from the NMME, are used frequently in seasonal forecasts for atmospheric variables and may have many uses in marine resource management.

In this study, precipitation and temperature forecasts during El Niño–Southern Oscillation (ENSO) events are examined in six models in the North American Multimodel Ensemble (NMME), including the CFSv2, CanCM3, CanCM4, the Forecast-Oriented Low Ocean Resolution (FLOR) version of GFDL CM2.5, GEOS-5, and CCSM4 models, by comparing the model-based ENSO composites to the observed. The composite analysis is conducted using the 1982–2010 hindcasts for each of the six models with selected ENSO episodes based on the seasonal oceanic Niño index just prior to the date the forecasts were initiated. Two types of composites are constructed over the North American continent: one based on mean precipitation and temperature anomalies and the other based on their probability of occurrence in a tercile-based system. The composites apply to monthly mean conditions in November, December, January, February, and March as well as to the 5-month aggregates representing the winter conditions. For anomaly composites, the anomaly correlation coefficient and root-mean-square error against the observed composites are used for the evaluation. For probability composites, a new probability anomaly correlation measure and a root-mean probability score are developed for the assessment. All NMME models predict ENSO precipitation patterns well during wintertime; however, some models have large discrepancies between the model temperature composites and the observed. The fidelity is greater for the multimodel ensemble as well as for the 5-month aggregates. February tends to have higher scores than other winter months. For anomaly composites, most models perform slightly better in predicting El Niño patterns than La Niña patterns. For probability composites, all models have superior performance in predicting ENSO precipitation patterns than temperature patterns.

An ordinary regression of predicted versus observed probabilities is presented as a direct and simple procedure for minimizing the Brier score (BS) and improving the attributes diagram. The main example applies to seasonal prediction of extratropical sea surface temperature by a global coupled numerical model. In connection with this calibration procedure, the probability anomaly correlation (PAC) is developed. This emphasizes the exact analogy of PAC and minimizing BS to the widely used anomaly correlation (AC) and minimizing mean squared error in physical units.

Background Vedolizumab has emerged as an important pillar of treatment in inflammatory bowel disease (IBD). However, for unknown reasons, not all patients respond to therapy. Earlier clinical studies suggested decreased response rates in the highest compared with medium dosage groups. Interestingly, vedolizumab has been shown to inhibit the homing of both regulatory (Treg) and effector T (Teff) cells and previous data from our group suggested different effect sizes in both populations. Thus, we hypothesised that the non-linear exposure–efficacy correlation might be explained by dose-dependent differential effects of vedolizumab on Treg and Teff homing. Therefore, we studied functional effects of different vedolizumab exposure levels on Treg and Teff cell trafficking. Methods The α4β7 expression on different human T-cell subsets as well as the binding characteristics of vedolizumab to these cells at different exposure levels was analysed via flow cytometry. Functional effects of different vedolizumab concentrations on the adhesion of Tregs and Teffs to mucosal addressin cell adhesion molecule 1 (MAdCAM-1) were analysed using dynamic in vitro adhesion assays, transmigration assays and in vivo homing assays in a humanised mouse model. The in vivo binding of vedolizumab to Tregs and Teffs in patients receiving therapy was quantified and correlated with the corresponding serum levels. Results We found a preferential binding of vedolizumab to Tregs at an exposure with 0.4 µg/ml vedolizumab that shifted to a preferential binding to Teffs at an exposure with 10 µg/ml. Further increase of vedolizumab to 50 µg/ml led to equal binding to Tregs and Teffs (Figure 1). Consistently, at 10 µg/ml, dynamic adhesion of Tregs to MAdCAM-1 was increased compared with Teffs, but no difference was noted at 50 µg/ml. Additionally, a higher number of Treg compared with Teff cells were able to transmigrate in a MAdCAM-1-dependent manner at a concentration of 10 µg/ml vedolizumab. Preliminary data from homing experiments in a humanised mouse model and from IBD patients treated with vedolizumab support the notion that differential binding preferences depending on the exposure level can also be observed in vivo. Conclusion Our findings support a dose-dependent differential binding of vedolizumab to different T-cell subpopulations and suggest that an optimal ‘window’ of exposure exists, in which effects on Teffs predominate over Tregs. While offering a potential explanation for earlier findings in dose-ranging studies, our data might lay the basis for the establishment of individualised dose optimisation in IBD patients.

Background While the number of therapeutic options for treating inflammatory bowel diseases (IBD) is increasing, evidence for rational treatment decisions is scarce in many cases. In particular, appropriate biomarkers to predict the response to the anti-α4β7 integrin antibody vedolizumab are currently lacking. Methods We performed a cohort study with 21 patients suffering from ulcerative colitis (UC), in which first-time treatment with vedolizumab was initiated. CD4+ T cells were isolated from the peripheral blood and dynamic adhesion to recombinant mucosal vascular addressin cell adhesion molecule (MAdCAM-)1 in vitro as well as the effect of vedolizumab on such adhesion in vitro was determined. The expression of α4β1 integrin on peripheral blood CD4+ T cells was quantified by flow cytometry. Electronic patient records were reviewed to determine clinical response to vedolizumab. Results Dynamic adhesion of peripheral blood CD4+ T cells to MAdCAM-1 and the reduction of adhesion following vedolizumab treatment in vitro were higher and the change in α4β1 expression on CD4+ T cells was different in vedolizumab responders and non-responders. Responders could be identified with high specificity and positive-predictive value. Conclusions Determining dynamic adhesion of CD4+ T cells to MAdCAM-1 and the in vitro response to vedolizumab before treatment initiation or dynamic integrin regulation in the early course of treatment seem to be promising tools to predict the clinical response to vedolizumab therapy. Larger prospective studies are warranted.

Although tissue-resident memory T cells (TRM cells) have been shown to regulate host protection in infectious disorders, their function in inflammatory bowel disease (IBD) remains to be investigated. Here we characterized TRM cells in human IBD and in experimental models of intestinal inflammation. Pro-inflammatory TRM cells accumulated in the mucosa of patients with IBD, and the presence of CD4+CD69+CD103+ TRM cells was predictive of the development of flares. In vivo, functional impairment of TRM cells in mice with double knockout of the TRM-cell-associated transcription factors Hobit and Blimp-1 attenuated disease in several models of colitis, due to impaired cross-talk between the adaptive and innate immune system. Finally, depletion of TRM cells led to a suppression of colitis activity. Together, our data demonstrate a central role for TRM cells in the pathogenesis of chronic intestinal inflammation and suggest that these cells could be targets for future therapeutic approaches in IBD.

Intestinal immune cell trafficking has been identified as a central event in the pathogenesis of inflammatory bowel diseases (IBD). Intensive research on different aspects of the immune mechanisms controlling and controlled by T cell trafficking and retention has led to the approval of the anti-α4β7 antibody vedolizumab, the ongoing development of a number of further anti-trafficking agents (ATAs) such as the anti-β7 antibody etrolizumab or the anti-MAdCAM-1 antibody ontamalimab and the identification of potential future targets like G-protein coupled receptor 15. However, several aspects of the biology of immune cell trafficking and regarding the mechanism of action of ATAs are still unclear, for example, which impact these compounds have on the trafficking of non-lymphocyte populations like monocytes and how precisely these therapies differ with regard to their effect on immune cell subpopulations. This review will summarise recent advances of basic science in the field of intestinal immune cell trafficking and discuss these findings with regard to different pharmacological approaches from a translational perspective.

Background:The anti-α4β7 integrin antibody vedolizumab is an established therapeutic option for the treatment of inflammatory bowel disease (IBD). It has also been successfully used in patients with chronic antibiotic-refractory pouchitis following proctocolectomey with ileal pouch-anal anastomosis. However, the expression and function of gut-homing markers as well as strategies to predict the response to vedolizumab in pouchitis are understudied so far.Methods:We used flow cytometry and dynamic adhesion assays to study the expression and function of gut-homing integrins on T cells from patients with pouchitis and controls as well as longitudinally during therapy of pouchitis with vedolizumab. Moreover, we describe clinical effects of vedolizumab in a cohort of patients with pouchitis.Results:T cells from patients with pouchitis express a specific profile of gut-homing integrins. Integrin α4β7 on T cells from patients with pouchitis mediates adhesion to mucosal addressin cell adhesion molecule (MAdCAM)-1, which can be blocked by vedolizumab in vitro. Vedolizumab efficiently treats pouchitis in a portion of patients and response correlates with dynamic adhesion profiles to MAdCAM-1.Conclusion:Our data suggest that T cell trafficking seems to be important for the pathogenesis of pouchitis and support the therapeutic use of vedolizumab. Integrin function might serve as a biomarker to predict response to vedolizumab.

The North American Multimodel Ensemble (NMME) forecasting system has been continuously producing seasonal forecasts since August 2011. The NMME, with its suite of diverse models, provides a valuable opportunity for characterizing forecast confidence using probabilistic forecasts. The current experimental probabilistic forecast product (in map format) presents the most likely tercile for the seasonal mean value, chosen out of above normal, near normal, or below normal categories, using a nonparametric counting method to determine the probability of each class. The skill of the 3-month-mean probabilistic forecasts of 2-m surface temperature (T2m), precipitation rate, and sea surface temperature is assessed using forecasts from the 29-yr (1982–2010) NMME hindcast database. Three forecast configurations are considered: a full six-model NMME; a “mini-NMME” with 24 members, four each from six models; and the 24-member CFSv2 alone. Skill is assessed on the cross-validated hindcasts using the Brier skill score (BSS); forecast reliability and resolution are also assessed. This study provides a baseline skill assessment of the current method of creating probabilistic forecasts from the NMME system. For forecasts in the above- and below-normal terciles for all variables and geographical regions examined in this study, BSS for NMME forecasts is higher than BSS for CFSv2 forecasts. Niño-3.4 forecasts from the full NMME and the mini-NMME receive nearly identical BSS that are higher than BSS for CFSv2 forecasts. Even systems with modest BSS, such as T2m in the Northern Hemisphere, have generally high reliability, as shown in reliability diagrams.

Before Cyclone Amphan took place in 2020, Cyclone Fani (May 2019) is the strongest pre-monsoon cyclone in the Bay of Bengal (BOB) since 1991, killing 90 people in eastern India and Bangladesh while causing US$1.81 billion of damages. Fani developed during a period of high concentration of anthropogenic aerosols in the BOB with abnormally high sea surface temperature (SST), thereby presenting an opportunity to understand the compound effects of atmospheric aerosols and regional climate warming on a tropical cyclone. A quantitative attribution analysis was conducted using the Weather Research and Forecasting model with chemistry (WRF-Chem) run at the convection-permitting (4 km) grid spacing, accompanied by an ensemble of coarser-resolution simulations to quantify the uncertainty. The removal of post-1990 trends in the tropospheric variables and SST from WRF-Chem’s initial conditions (IC) and boundary conditions (BC, including the lateral and lower boundary conditions) resulted in a reduction of cyclone precipitation by about 51% during the 5 d of April 28-May 2. The removal of tropospheric warming shows approximately twice as strong an effect on Fani (39% reduction in precipitation) as that of SST warming (22% reduction). When aerosol’s direct and indirect effects were removed from the simulations, i.e., no aerosol influence on radiation and cloud microphysics, Fani initially strengthened but later weakened, as measured by geopotential height and precipitation amounts. These results suggest that aerosol and its interaction with the atmosphere acted to mitigate the strengthening effect of anthropogenic warming on Fani, but was not strong enough to entirely counteract it. Although the ensemble of coarser simulations appears to overestimate Cyclone Fani in terms of precipitation, the direction of the effects is in agreement with that obtained from the 4 km simulations. Given the increasing anthropogenic aerosols in the BOB, future attribution studies using more sophisticated dynamical aerosol models on BOB tropical cyclones are urged.

Highlights • Campaigns can recruit African Americans to glaucoma screenings and studies. • Marketing with community partners successfully reached the target audience. • Radio commercials and postcards were most cost-effective in recruiting patients., Our objective was to determine which messaging approaches from a marketing campaign were most effective in recruiting African American individuals to a glaucoma screening and research study. We conducted a multimedia marketing campaign in Philadelphia from 01/31/2018 to 06/30/2018. Messaging approaches included radio advertisements and interviews (conducted in partnership with a local radio station with a large African American listener base), print materials, event tables, and online postings. Participants received free glaucoma screenings and the opportunity to enroll in our glaucoma genetics study. These screenings allowed individuals with glaucoma to receive a full examination and treatment plan with a glaucoma specialist, as well as to contribute to future efforts to identify genetic variants underlying this disease. We compared inquiry, enrollment, and cost yield for each messaging approach. Our campaign resulted in 154 unique inquiries, with 98 patients receiving glaucoma screenings (64%) and 60 patients enrolling in our study (39%). Commercials on WURD radio yielded the highest number of inquiries (62%) and enrollments (62%), but at relatively high cost ($814/enrolled patient). The most inexpensive approach that yielded more than five enrollments was postcards ($429/enrolled patient). Our campaign suggests that high-frequency commercials and postcards distributed at targeted healthcare locations are particularly effective and affordable options for connecting with the African American community. Our findings can help to inform recruitment efforts for other understudied diseases in minority populations.

Background: Anti-integrin therapy is a new frontline strategy in the treatment of inflammatory bowel diseases (IBD). The anti-β7 integrin antibody etrolizumab is currently being investigated for safety and efficacy in Crohn’s disease (CD) and ulcerative colitis (UC) in several phase III trials. Mechanistically, etrolizumab is known to block β7 integrin ligand binding and reduces intestinal trafficking of β7-expressing cells. Etrolizumab blocks β7 integrin ligand binding and reduces β7-positive lymphocyte migration and retention in the inflamed gut mucosa, but the exact mechanisms by which this inhibition occurs are not fully understood. Methods: Cellular effects of etrolizumab or etrolizumab surrogate antibody (etrolizumab-s) were investigated in cell culture models and analyzed by flow cytometry, fluorescence microscopy, ImageStream®, stimulated emission depletion (STED) microscopy and functional dynamic in vitro adhesion assays. Moreover, effects on α4β7 integrin were compared with the pharmacodynamically similar antibody vedolizumab. Results: As demonstrated by several different approaches, etrolizumab and etrolizumab-s treatment led to internalization of β7 integrin. This resulted in impaired dynamic adhesion to MAdCAM-1. Internalized β7 integrin localized in endosomes and re-expression of β7 was dependent on de novo protein synthesis. In vitro etrolizumab treatment did not lead to cellular activation or cytokine secretion and did not induce cytotoxicity. Internalization of α4β7 integrin was increased with etrolizumab compared with vedolizumab. Discussion: Our data suggest that etrolizumab does not elicit secondary effector functions on the single cell level. Integrin internalization may be an important mechanism of action of etrolizumab, which might explain some but not all immunological effects observed with etrolizumab.

Gut homing of immune cells is important for the pathogenesis of inflammatory bowel diseases (IBD). Integrin-dependent cell adhesion to addressins is a crucial step in this process and therapeutic strategies interfering with adhesion have been successfully established. The anti-α4β7 integrin antibody, vedolizumab, is used for the clinical treatment of Crohn's disease (CD) and ulcerative colitis (UC) and further compounds are likely to follow. The details of the adhesion procedure and the action mechanisms of anti-integrin antibodies are still unclear in many regards due to the limited available techniques for the functional research in this field. Here, we present a dynamic adhesion assay for the functional analysis of human cell adhesion under flow conditions and the impact of anti-integrin therapies in the context of IBD. It is based on the perfusion of primary human cells through addressin-coated ultrathin glass capillaries with real-time microscopic analysis. The assay offers a variety of opportunities for refinements and modifications and holds potentials for mechanistic discoveries and translational applications.

Although tissue-resident memory T cells (T

In the post-colonial era, social movements in the Commonwealth Caribbean have empowered citizens to reclaim, redefine and further develop their identity. These movements, combined with a history of colonialism and transatlantic slavery in the region, have yielded a Caribbean culture “too diverse to be labeled.” Indeed, the Caribbean culture is composed of “a bastion of discrete identities as well as quarries of very invaluable raw material that can be used to build the bridges across cultural boundaries.” These distinct but potentially overlapping identities make the Commonwealth Caribbean a truly pluralistic region, at least at the cultural and social level. As modern legal and political systems, however, the states of the Commonwealth Caribbean have, in many ways, failed to sufficiently protect the non-dominant groups within Caribbean. Indeed, attempts to balance the majoritarian demands of democracy against the pluralist notion of minority rights protection have landed largely on the side of majorities.

Background Although anti-adhesion therapies are a novel mainstay in the treatment of inflammatory bowel diseases (IBDs), the mechanisms controlling integrin-dependent gut homing are poorly elucidated, and the available techniques for translational functional investigations are limited. Methods We used dynamic adhesion assays to study adhesion of CD4+ T cells, CD8+ T cells, CD19+ B cells, and granulocytes to the addressins MAdCAM-1, VCAM-1, and ICAM-1. The effects of vedolizumab, natalizumab, etrolizumab-s, anti-CD11a, and anti-CD18 antibodies were explored. Results Adhesion of peripheral blood leukocytes from IBD patients and control donors could be validly assessed, and integrin-mediated addressin adhesion could be specifically inhibited by anti-integrin antibodies. Numbers of adhering cells were partly, but not completely, related to integrin expression. Vedolizumab and etrolizumab-s resulted in similar reduction of adhesion to MAdCAM-1, and preliminary data proposed an association of dynamic adhesion to MAdCAM-1 with response to vedolizumab therapy. Conclusions Dynamic adhesion assays are an easy and broadly applicable method for IBD research that is useful for future translational studies and potentially also for supporting clinical treatment decisions. 10.1093/ibd/izy077_video1izy077_Video_15786486962001.

The El Niño of 2015/16 was among the strongest El Niño events observed since 1950 and took place almost two decades after the previous major event in 1997/98. Here, perspectives of the event are shared by scientists from three national meteorological or climate services that issue regular operational updates on the status and prediction of El Niño–Southern Oscillation (ENSO). Public advisories on the unfolding El Niño were issued in the first half of 2015. This was followed by significant growth in sea surface temperature (SST) anomalies, a peak during November 2015–January 2016, subsequent decay, and its demise during May 2016. The life cycle and magnitude of the 2015/16 El Niño was well predicted by most models used by national meteorological services, in contrast to the generally overexuberant model predictions made the previous year. The evolution of multiple atmospheric and oceanic measures demonstrates the rich complexity of ENSO, as a coupled ocean–atmosphere phenomenon with pronounced global impacts. While some aspects of the 2015/16 El Niño rivaled the events of 1982/83 and 1997/98, we show that it also differed in unique and important ways, with implications for the study and evaluation of past and future ENSO events. Unlike previous major El Niños, remarkably above-average SST anomalies occurred in the western and central equatorial Pacific but were milder near the coast of South America. While operational ENSO systems have progressed markedly over the past several decades, the 2015/16 El Niño highlights several challenges that will continue to test both the research and operational forecast communities.

Forecast skill and potential predictability of 2-m temperature, precipitation rate, and sea surface temperature are assessed using 29 yr of hindcast data from models included in phase 1 of the North American Multimodel Ensemble (NMME) project. Forecast skill is examined using the anomaly correlation (AC); skill of the bias-corrected ensemble means (EMs) of the individual models and of the NMME 7-model EM are verified against the observed value. Forecast skill is also assessed using the root-mean-square error. The models’ representation of the size of forecast anomalies is also studied. Predictability was considered from two angles: homogeneous, where one model is verified against a single member from its own ensemble, and heterogeneous, where a model’s EM is compared to a single member from another model. This study provides insight both into the physical predictability of the three fields and into the NMME and its contributing models. Most of the models in the NMME have fairly realistic spread, as represented by the interannual variability. The NMME 7-model forecast skill, verified against observations, is equal to or higher than the individual models’ forecast ACs. Two-meter temperature (T2m) skill matches the highest single-model skill, while precipitation rate and sea surface temperature NMME EM skill is higher than for any single model. Homogeneous predictability is higher than reported skill in all fields, suggesting there may be room for some improvement in model prediction, although there are many regional and seasonal variations. The estimate of potential predictability is not overly sensitive to the choice of model. In general, models with higher homogeneous predictability show higher forecast skill.

CD4(+) follicular helper T cells (T(FH) cells) are essential for germinal center (GC) responses and long-lived antibody responses. Here we report that naive CD4(+) T cells deficient in the transcription factor Foxp1 'preferentially' differentiated into T(FH) cells, which resulted in substantially enhanced GC and antibody responses. We found that Foxp1 used both constitutive Foxp1A and Foxp1D induced by stimulation of the T cell antigen receptor (TCR) to inhibit the generation of T(FH) cells. Mechanistically, Foxp1 directly and negatively regulated interleukin 21 (IL-21); Foxp1 also dampened expression of the costimulatory molecule ICOS and its downstream signaling at early stages of T cell activation, which rendered Foxp1-deficient CD4(+) T cells partially resistant to blockade of the ICOS ligand (ICOSL) during T(FH) cell development. Our findings demonstrate that Foxp1 is a critical negative regulator of T(FH) cell differentiation.

The recent U.S. National Academies report, Assessment of Intraseasonal to Interannual Climate Prediction and Predictability, was unequivocal in recommending the need for the development of a North American Multimodel Ensemble (NMME) operational predictive capability. Indeed, this effort is required to meet the specific tailored regional prediction and decision support needs of a large community of climate information users. The multimodel ensemble approach has proven extremely effective at quantifying prediction uncertainty due to uncertainty in model formulation and has proven to produce better prediction quality (on average) than any single model ensemble. This multimodel approach is the basis for several international collaborative prediction research efforts and an operational European system, and there are numerous examples of how this multimodel ensemble approach yields superior forecasts compared to any single model. Based on two NOAA Climate Test bed (CTB) NMME workshops (18 February and 8 April 2...

The second version of the NCEP Climate Forecast System (CFSv2) was made operational at NCEP in March 2011. This version has upgrades to nearly all aspects of the data assimilation and forecast model components of the system. A coupled reanalysis was made over a 32-yr period (1979–2010), which provided the initial conditions to carry out a comprehensive reforecast over 29 years (1982–2010). This was done to obtain consistent and stable calibrations, as well as skill estimates for the operational subseasonal and seasonal predictions at NCEP with CFSv2. The operational implementation of the full system ensures a continuity of the climate record and provides a valuable up-to-date dataset to study many aspects of predictability on the seasonal and subseasonal scales. Evaluation of the reforecasts show that the CFSv2 increases the length of skillful MJO forecasts from 6 to 17 days (dramatically improving subseasonal forecasts), nearly doubles the skill of seasonal forecasts of 2-m temperatures over the United States, and significantly improves global SST forecasts over its predecessor. The CFSv2 not only provides greatly improved guidance at these time scales but also creates many more products for subseasonal and seasonal forecasting with an extensive set of retrospective forecasts for users to calibrate their forecast products. These retrospective and real-time operational forecasts will be used by a wide community of users in their decision making processes in areas such as water management for rivers and agriculture, transportation, energy use by utilities, wind and other sustainable energy, and seasonal prediction of the hurricane season.

In the version of this article initially published, a portion of the Acknowledgements section ("the Clinical Research Group CEDER of the German Research Council (DFG)") was incorrect. The correct statement is as follows: "...the Collaborative Research Center TRR241 of the German Research Council (DFG)...". The error has been corrected in the HTML and PDF version of the article.

Forecasts for extremes in short-term climate (monthly means) are examined to understand the current prediction capability and potential predictability. This study focuses on 2-m surface temperature and precipitation extremes over North and South America, and sea surface temperature extremes in the Niño-3.4 and Atlantic hurricane main development regions, using the Climate Forecast System (CFS) global climate model, for the period of 1982–2010. The primary skill measures employed are the anomaly correlation (AC) and root-mean-square error (RMSE). The success rate of forecasts is also assessed using contingency tables. The AC, a signal-to-noise skill measure, is routinely higher for extremes in short-term climate than those when all forecasts are considered. While the RMSE for extremes also rises, especially when skill is inherently low, it is found that the signal rises faster than the noise. Permutation tests confirm that this is not simply an effect of reduced sample size. Both 2-m temperature and precipitation forecasts have higher anomaly correlations in the area of South America than North America; credible skill in precipitation is very low over South America and absent over North America, even for extremes. Anomaly correlations for SST are very high in the Niño-3.4 region, especially for extremes, and moderate to high in the Atlantic hurricane main development region. Prediction skill for forecast extremes is similar to skill for observed extremes. Assessment of the potential predictability under perfect-model assumptions shows that predictability and prediction skill have very similar space–time dependence. While prediction skill is higher in CFS version 2 than in CFS version 1, the potential predictability is not.

High quality dilute nitride subcells for multijunction solar cells are achieved using GaInNAsSb. The effects on device performance of Sb composition, strain and purity of the GaInNAsSb material are discussed. New world records in efficiency have been set with lattice-matched InGaP/GaAs/GaInNAsSb triple junction solar cells and a roadmap to 50% efficiency with lattice-matched multijunction solar cells using GaInNAsSb is shown.

The article reports on the subtlety of the truth about El Nino and La Nin climate patterns which often get blame for extreme weather. Topics include the tendency of the media and meteorologist to link extreme weather to the climate patterns, the inconsistency of the climate patterns which failed to bring expected heavy rains to southern California in 2015-2016, and the continued recurrence of El Ninos and La Nins for thousands of years.

Objective This study tested whether positive response to short-term treatment for adolescent major depressive disorder (MDD) would have the secondary benefit of preventing subsequent alcohol use disorders (AUD) or substance use disorders (SUD). Method For 5 years, we followed 192 adolescents (56.2% female; 20.8% minority) who had participated in the Treatment for Adolescents with Depression Study (TADS; TADS Team, 2004) and who had no prior diagnoses of AUD or SUD. TADS initial treatments were cognitive behavior therapy (CBT), fluoxetine alone (FLX), the combination of CBT and FLX (COMB), or clinical management with pill placebo (PBO). We used both the original TADS treatment response rating and a more restrictive symptom count rating. During follow-up, diagnostic interviews were completed at 6- or 12-month intervals to assess onset of AUD or SUD as well as MDD recovery and recurrence. Results Achieving a positive response to MDD treatment was unrelated to subsequent AUD but predicted a lower rate of subsequent SUD, regardless of the measure of positive response (11.65% vs. 24.72%, or 10.0% vs. 24.5%, respectively). Type of initial MDD treatment was not related to either outcome. Prior to depression treatment, greater involvement with alcohol or drugs predicted later AUD or SUD, as did older age (for AUD) and more comorbid disorders (for SUD). Among those with recurrent MDD and AUD, AUD preceded MDD recurrence in 24 of 25 cases. Conclusion Effective short-term adolescent depression treatment significantly reduces the rate of subsequent SUD but not AUD. Alcohol or drug use should be assessed prior to adolescent MDD treatment and monitored even after MDD recovery.

This study examines the characteristics of cold-season (November–March) daily precipitation over the contiguous United States during active periods of the Madden–Julian oscillation (MJO). A large response in the precipitation rate anomaly is found over the eastern United States when MJO-related enhanced tropical convection is moving through the far western to central Pacific (conventionally known as phases 5, 6, and 7 of the MJO). Positive anomalies occur in the region of the eastern Mississippi River basin, and negative anomalies occur in the Southeast. The relative stability of this pattern throughout the three phases suggests that they can be considered together. During phases 5–7, the central United States has a daily precipitation rate between 110% and 150% of normal, while the precipitation rate over much of Florida is less than 70% of normal. Much of the lower Mississippi River basin region receives somewhat more frequent daily precipitation during MJO phases 5–7, but a greater increase is found in the daily precipitation intensity, suggesting more intense storms. On the other hand, Florida has substantially fewer daily precipitation events, with a smaller decrease in the intensity. To understand the atmospheric mechanisms related to the above shifts in daily precipitation, elements of the atmospheric circulation were examined. Positive moisture flux convergence anomalies, which have been linked to increased precipitation rate and intensity, are found in the region of increased precipitation rate during MJO phases 5–7. During those phases, the North American jet stream is shifted northward, likely leading to a higher incidence of storms over the lower Mississippi River basin and fewer storms over Florida. This is supported by the fact that the storm track also shows increased activity over the central United States during MJO phases 5–7.

A comparison of the statistics of daily precipitation over the conterminous United States is carried out using gridded station data and three generations of reanalysis products in use at the National Centers for Environmental Prediction (NCEP). The reanalysis products are the NCEP–NCAR reanalysis (Kalnay et al.), the NCEP–Department of Energy (DOE) reanalysis (Kanamitsu et al.), and the NCEP Climate Forecast System (CFS) reanalysis (Saha et al.). Several simple measures are used to characterize relationships between the observations and the reanalysis products, including bias, precipitation probability, variance, and correlation. Seasonality is accounted for by examining these measures for four nonoverlapping seasons, using daily data in each case. Relationships between daily precipitation and El Niño–Southern Oscillation (ENSO) phase are also considered. It is shown that the CFS reanalysis represents a clear improvement over the earlier reanalysis products, though significant biases remain. Comparisons of the error patterns in the reanalysis products provide a suitable basis for confident conversion of the Climate Prediction Center (CPC) operational monitoring and prediction products to the new generation of analyses based on CFS.

Adolescents with depression and high levels of oppositionality often are particularly difficult to treat. Few studies, however, have examined treatment outcomes among youth with both externalizing and internalizing problems. This study examines the effect of fluoxetine, cognitive behavior therapy (CBT), the combination of fluoxetine and CBT, and placebo on co-occurring oppositionality within a sample of depressed adolescents. All treatments resulted in decreased oppositionality at 12 weeks. Adolescents receiving fluoxetine, either alone or in combination with CBT, experienced greater reductions in oppositionality than adolescents not receiving antidepressant medication. These results suggest that treatments designed to alleviate depression can reduce oppositionality among youth with a primary diagnosis of depression.

This study examines the seasonal characteristics of daily precipitation over the United States using the North American Regional Reanalysis (NARR). To help understand the physical mechanisms that contribute to changes in the characteristics of daily precipitation, vertically integrated moisture flux convergence (MFC) and precipitable water were included in the study. First, an analysis of the NARR precipitation was carried out because while observed precipitation is indirectly assimilated in the system, differences exist. The NARR mean seasonal amount is very close to that of observations throughout the year, although NARR exhibits a slight systematic bias toward more-frequent, lighter precipitation. Particularly during summer, the precipitation intensity and the probability distribution function (PDF) indicate that NARR somewhat underestimates extremes and overestimates lighter events in the eastern half of the United States. The intensity and PDF of moisture flux convergence exhibit a strong similarity to those of precipitation, suggesting a link between strong MFC and precipitation extremes. On the other hand, the relationship between the precipitable water and precipitation PDFs is weaker, based on the lack of agreement of their gamma distribution parameters. The dependence of the precipitation PDF on the lower-frequency modulation of ENSO was examined. During El Niño winters, the Southwest and central United States, Gulf of Mexico region, and southeastern coast have greater precipitation intensity and extremes than during La Niña, and the Ohio River and Red River basins have lower intensity and fewer extreme events. During summer, the northern Rocky Mountains receive higher intensity precipitation with more extreme events. Most areas where the change in the daily mean precipitation between ENSO phases is large have greater shifts in the extreme tail of the PDF. The ENSO-related response of moisture flux convergence is similar to that of precipitation. ENSO-related shifts in the precipitation PDF do not appear to have a strong relationship to the shifts in precipitable water.

Background The anti-TNF-α agents adalimumab, infliximab and etanercept are indicated for a variety of autoimmune diseases such as rheumatoid arthritis (RA), Crohn's disease (CD), ankylosing spondylitis (AS), psoriatic arthritis (PsA) and psoriasis (Pso). In some patients treated for nonpsoriatic conditions such as rheumatoid arthritis and Crohn's disease, these agents have been associated with the appearance of psoriasis (either its emergence or exacerbation)—a term previously coined TNF-α antagonist induced psoriasis. Objective This article reviews published data demonstrating this phenomenon. Methods Studies with English abstracts between 2000–2008, identified in MEDLINE and PUBMED with keywords anti-TNF, psoriasis, TNF-α antagonist and induced, were retrospectively reviewed. Results An association between use of anti-TNF agents and the appearance of psoriasis was seen in a total of 219 patients from 38 reports. Conclusion There is an association between use of anti-TNF agents and appearance of psoriasis, but the specific nature of the relationship is unknown. Recent studies help to delineate patient characteristics common among the group, as well as theorize proposed mechanisms for the emergence of psoriasis. At this time, however, further investigation into this multi-factorial condition is needed.

The structure of the diurnal cycle of warm-season precipitation and its associated fields during the North American monsoon are examined for the core monsoon region and for the southwestern United States, using a diverse set of observations, analyses, and forecasts from the North American Monsoon Experiment field campaign of 2004. Included are rain gauge and satellite estimates of precipitation, Eta Model forecasts, and the North American Regional Reanalysis (NARR). Daily rain rates are of about the same magnitude in all datasets with the exception of the Climate Prediction Center (CPC) Morphing (CMORPH) technique, which exhibits markedly higher precipitation values. The diurnal cycle of precipitation within the core region occurs earlier in the day at higher topographic elevations, evolving with a westward shift of the maximum. This shift appears in the observations, reanalysis, and, while less pronounced, in the model forecasts. Examination of some of the fields associated with this cycle, including convective available potential energy (CAPE), convective inhibition (CIN), and moisture flux convergence (MFC), reveals that the westward shift appears in all of them, but more prominently in the latter. In general, warm-season precipitation in southern Arizona and parts of New Mexico shows a strong effect due to northward moisture surges from the Gulf of California. A reported positive bias in the NARR northward winds over the Gulf of California limits their use with confidence for studies of the moist surges along the Gulf; thus, the analysis is complemented with operational analysis and the Eta Model short-term simulations. The nonsurge diurnal cycle of precipitation lags the CAPE maximum by 6 h and is simultaneous with a minimum of CIN, while the moisture flux remains divergent throughout the day. During surges, CAPE and CIN have modifications only to the amplitude of their cycles, but the moisture flux becomes strongly convergent about 6 h before the precipitation maximum, suggesting a stronger role in the development of precipitation.

This chapter provides a useful map around roadblocks that therapists may encounter in everyday practice. Each section addresses a different stumbling block, with a review of relevant literature, as well as case examples and practical advice on overcoming various problems. Case conceptualization is recommended for understanding and navigating roadblocks. Sections also address concerns related to “difficult-to-treat” patients, application of session structure, resistance, and hopelessness. The chapter considers how therapist factors, patient factors, their interaction, and the patient's environment and psychopathology all influence treatment outcome. Emphasis is placed on helping patients to succeed at homework, since homework completion correlates with success in cognitive behavioral therapy. The goal of the chapter is to provide clinicians with practical strategies to overcome difficulties encountered in therapy. Keywords: cognitive behavioral therapy; resistance; case conceptualization; session structure; homework; treatment goals; key problems; summaries

Major depressive disorder in adolescents is common and impairing. Efficacious treatments have been developed, but little is known about longer-term outcomes, including recurrence.To determine whether adolescents who responded to short-term treatments or who received the most efficacious short-term treatment would have lower recurrence rates, and to identify predictors of recovery and recurrence.Naturalistic follow-up study.Twelve academic sites in the United States.One hundred ninety-six adolescents (86 males and 110 females) randomized to 1 of 4 short-term interventions (fluoxetine hydrochloride treatment, cognitive behavioral therapy, their combination, or placebo) in the Treatment for Adolescents With Depression Study were followed up for 5 years after study entry (44.6% of the original Treatment for Adolescents With Depression Study sample).Recovery was defined as absence of clinically significant major depressive disorder symptoms on the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version interview for at least 8 weeks, and recurrence was defined as a new episode of major depressive disorder following recovery.Almost all participants (96.4%) recovered from their index episode of major depressive disorder during the follow-up period. Recovery by 2 years was significantly more likely for short-term treatment responders (96.2%) than for partial responders or nonresponders (79.1%) (P.001) but was not associated with having received the most efficacious short-term treatment (the combination of fluoxetine and cognitive behavioral therapy). Of the 189 participants who recovered, 88 (46.6%) had a recurrence. Recurrence was not predicted by full short-term treatment response or by original treatment. However, full or partial responders were less likely to have a recurrence (42.9%) than were nonresponders (67.6%) (P = .03). Sex predicted recurrence (57.0% among females vs 32.9% among males; P = .02).Almost all depressed adolescents recovered. However, recurrence occurs in almost half of recovered adolescents, with higher probability in females in this age range. Further research should identify and address the vulnerabilities to recurrence that are more common among young women.

Typically developing children frequently participate in community recreation activities that enhance their social/emotional and physical development. The inclusion of children with developmental disabilities in these activities continues to be a challenge. This case report investigated the feasibility of including a child with Down syndrome in a community performing arts program. The participant is an 11-year-old female with Down syndrome and mild cognitive impairment. The participant was enrolled in a 14-week performing arts session that included a combination of acting, voice, and dance instruction. She participated in the program with the support of a one-on-one assistant who was a physical therapy student. The assistant facilitated learning the choreography, appropriate socialization, and positioning on the stage. Peer helpers were used to allow for greater independence toward the end of the session and for the final performance. The participant completed the final performance without the one-on-one assistant. The participant's mother completed the PedsQL before and after the performance, and the participant's scaled scores increased in all subsets except for emotional function and the total scales score increased from 51 to 57. With appropriate modifications and the right child/program fit, children with developmental disabilities such as Down syndrome can successfully be included in community programs. Physical therapists can assist families and community programs to make developmentally appropriate modifications to enhance participation.

Background Common methods for determination of fusional vergence ranges make use of rotary prisms in the phoropter or prism bars out of the phoropter. This study compared near fusional vergence ranges with rotary prisms with those with prism bars. Methods Fifty young adults served as subjects. Odd-numbered subjects had rotary prism vergences performed before prism bar vergences. For even-numbered subjects, prism bar vergences were done first. Base-in (BI) vergences were done before base-out (BO) vergences with both rotary prisms and prism bars. A coefficient of agreement was calculated by multiplying the standard deviation of the individual subject differences between rotary prisms and prism bars by 1.96, to approximate the range within which the 2 tests would agree 95% of the time. Results The lowest coefficient of agreement was 7.3Δ for the BI recovery. The others were high, ranging from 15.4Δ for the BO recovery to 19.5Δ for the BO break. Conclusion Fusional vergence ranges determined by prism bars out of the phoropter cannot be used interchangeably with those determined by phoropter rotary prisms for the purpose of follow-up on individual patients or for the purpose of comparison with norms.

Studies suggest that deficits in social problem-solving may be associated with increased risk of depression and suicidality in children and adolescents. It is unclear, however, which specific dimensions of social problem-solving are related to depression and suicidality among youth. Moreover, rational problem-solving strategies and problem-solving motivation may moderate or predict change in depression and suicidality among children and adolescents receiving treatment. The effect of social problem-solving on acute treatment outcomes were explored in a randomized controlled trial of 439 clinically depressed adolescents enrolled in the Treatment for Adolescents with Depression Study (TADS). Measures included the Children's Depression Rating Scale-Revised (CDRS-R), the Suicidal Ideation Questionnaire – Grades 7-9 (SIQ-Jr), and the Social Problem Solving Inventory-Revised (SPSI-R). A random coefficients regression model was conducted to examine main and interaction effects of treatment and SPSI-R subscale scores on outcomes during the 12-week acute treatment stage. Negative problem orientation, positive problem orientation, and avoidant problem-solving style were non-specific predictors of depression severity. In terms of suicidality, avoidant problem-solving style and impulsiveness/carelessness style were predictors, whereas negative problem orientation and positive problem orientation were moderators of treatment outcome. Implications of these findings, limitations, and directions for future research are discussed.

Background: Factors that distinguish depressed individuals who become hopeless from those who do not are poorly understood. Method: In this study, predictors of hopelessness were examined in a sample of 439 clinically depressed adolescents participating in the Treatment for Adolescents with Depression Study (TADS). The total score of the Beck Hopelessness Scale (BHS) was used to assess hopelessness at baseline. Multiple regression and logistic regression analyses were conducted to evaluate the extent to which variables were associated with hopelessness and determine which cluster of measures best predicted clinically significantly hopelessness. Results: Hopelessness was associated with greater depression severity, poor social problem-solving, cognitive distortions, and family conflict. View of self, view of the world, internal attributional style, need for social approval, positive problem-solving orientation, and family problems consistently emerged as the best predictors of hopelessness in depressed youth. Conclusions: Cognitive and familial factors predict those depressed youth who have high levels of hopelessness.