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A automedicacao pode ser considerada a utilizacao de farmacos com a finalidade de promover a saude e os efeitos imediatos para atender uma situacao que nao exista maior complexidade voltada para o tratamento de sintomas adversos. O objetivo desse estudo foi apresentar os riscos oferecidos pela automedicacao de anti-inflamatorios em pacientes pediatricos. O estudo trata-se de uma revisao sistematica da literatura, com o modelo de analise para o estudo sera baseado na metodologia de Pratica Baseada em Evidencias (PBE) com a utilizacao da Preferred Reporting Items for Systematic (Prisma) para a obtencao do (checklist) e realizacao de meta-analise dos estudos coletados, cujo metodo do estudo foi realizado a partir da metodologia Prisma com criterios de inclusao e exclusao pre-definidos e a utilizacao das estrategias de busca. Os resultados do estudo foram apresentados conforme a aplicabilidade do metodo de pesquisa com a utilizacao dos criterios de inclusao e exclusao para a revisao sistematica, tendo como quantitativo de analise um total de 11 publicacoes. Concluiu-se que o presente estudo, por meio da revisao sistematica, apresentou uma miscelânea de pesquisas que desenvolveram analises clinicas sobre a automedicacao de AINEs em pacientes pediatricos, demonstrando que o uso irracional na administracao e consumo dessa categoria de medicamento pode afetar a saude do paciente pediatrico, onde se torna necessario a Atencao Farmaceutica e o acompanhamento medico especializado sao fundamentais para a eficacia de um determinado tratamento.

Objective To develop and validate new Juvenile Arthritis Disease Activity Score 10 (JADAS10) and clinical JADAS10 (cJADAS10) cutoffs to separate the states of inactive disease (ID), minimal disease activity (MiDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with oligoarthritis and with rheumatoid factor-negative polyarthritis, based on subjective disease assessment by the treating pediatric rheumatologist. Methods The cutoffs definition cohort was composed of 1,936 patients included in the multinational Epidemiology, Treatment and Outcome of Childhood Arthritis (EPOCA) study. Using the subjective physician rating as an external criterion, 4 methods were applied to identify the cutoffs: mapping, Youden index, 90% specificity, and maximum agreement. The validation cohort included 4,014 EPOCA patients, patients from 2 randomized trials, and 88 patients from the PharmaChild registry. Cutoff validation was conducted by assessing discriminative and predictive ability. Results The JADAS10 cutoffs were 1.4, 4, and 13, respectively, for oligoarthritis and 2.7, 6, and 17, respectively, for polyarthritis. The cJADAS10 cutoffs were 1.1, 4, and 12, respectively, for oligoarthritis and 2.5, 5, and 16, respectively, for polyarthritis. The cutoffs discriminated strongly among different levels of pain and morning stiffness, between patients who were and those who were not prescribed a new medication, and between different levels of improvement in clinical trials. Achievement of ID and MiDA according to the new JADAS cutoffs at least twice in the first year of disease predicted better outcome at 2 years. Conclusion The 2021 JADAS and cJADAS cutoffs revealed good metrologic properties in both definition and validation samples, and are therefore suitable for use in clinical trials and routine practice.

Juvenile primary fibromyalgia syndrome (JPFS) is a chronic musculoskeletal pain syndrome affecting children and adolescents. In part one of this review, we discussed the epidemiology, etiology, pathogenesis, clinical manifestations and diagnosis of JPFS. Part two focuses on the treatment and prognosis of JPFS. Early intervention is important. The standard of care is multidisciplinary, combining various modalities—most importantly, exercise and cognitive behavioral therapy. Prognosis varies and symptoms may persist into adulthood.

The purpose of this paper is to determine trends in the wages and living standards of male agricultural labourers in Central Chile during the agrarian expansion, c. 1870-1930. We found that nominal wages increased eightfold; this is relevant because wage labour became the main rural labour regime in this period. Nominal wages rose steadily from the early 1870s until 1910, and with significant fluctuations thereafter, before plummeting with the Great Depression. Real wages also increased, but only slightly. Furthermore, during certain short periods, agricultural labourers' real wages were similar to or higher than those of low-skilled urban workers. However, the persistent gap between agricultural and non-agricultural wages was one of the causal factors of the outmigration of rural workers.

Made available in DSpace on 2022-04-28T17:22:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-01 Janssen Research & Development, LLC Objectives. To assess efficacy, pharmacokinetics (PK) and safety of intravenous (i.v.) golimumab in patients with polyarticular-course JIA (pc-JIA). Methods. Children aged 2 to = 2months received 80 mg/m(2) golimumab at weeks 0, 4, then every 8 weeks through week 52 plus MTX weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUC(ss)) over an 8-week dosing interval at weeks 28 and 52, respectively. JIA ACR response and safety were also assessed. Results. In total, 127 children were treated with i.v. golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70% and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUC(ss) were 0.40 mu g/ml and 399 mu g. day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUC(ss) were consistent across age categories and comparable to i.v. golimumab dosed 2mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including one death due to septic shock. Conclusion. Body surface area-based dosing of i.v. golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA. IRCCS Ist Giannina Gaslini Clin Pediat & Reumatol, PRINTO, Genoa, Italy Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH USA Univ Autonoma Chihuahua, Fac Med, Circuito Univ Campus 2, Chihuahua, Mexico Panorama Med Ctr, Cape Town, South Africa Hosp Mexico Americano, Ctr Reumatol & Autoinmunidad CREA, Guadalajara, Jalisco, Mexico Ctr Med Privado Reumatol, Rheumatol Sect, San Miguel De Tucuman, Tucuman, Argentina Randall Childrens Hosp Legacy Emanuel, Portland, OR USA Univ Calgary, Alberta Childrens Hosp, Cumming Sch Med, Dept Pediat, Calgary, AB, Canada Pontificia Univ Catolica Chile, Sch Med, Dept Pediat Infect Dis & Immunol, Santiago, Chile Hosp Pedro de Elizalde, Rheumatol Sect, Buenos Aires, DF, Argentina Univ Utah, Pediat Rheumatol, Salt Lake City, UT USA Bashkir State Med Univ Minist Healthcare Russian, Fed State Budget Educ Inst Higher Educ, Ufa, Russia Univ Cape Town, Red Cross War Mem Childrens Hosp, Cape Town, South Africa Univ Cape Town, Groote Schuur Hosp, Paediat Rheumatol, Cape Town, South Africa Clin Hosp 5, Pediat Dept, Tolyatti, Russia Univ Fed Sao Paulo, Escola Paulista Med, Pediat, Sao Paulo, Brazil Inst CAICI, Rheumatol, Rosario, Argentina Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil UNESP, Hosp Clin Botucatu Med Univ, Paediat Dept, Botucatu, SP, Brazil Hosp Infantil Mexico Dr Federico Gomez, Med Interna & Reumatol, Mexico City, DF, Mexico Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA Janssen Res & Dev LLC, Spring House, PA USA Janssen Res & Dev LLC, Raritan, NJ USA Univ Genoa, Dipartimento Neurosci Riabilitaz Oftalmol Genet &, Genoa, Italy UNESP, Hosp Clin Botucatu Med Univ, Paediat Dept, Botucatu, SP, Brazil

The antiapoptotic protein BCL2 plays critical roles in regulating lymphocyte development and immune responses, and has also been implicated in tumorigenesis and tumor survival. However, it is unknown whether BCL2 is critical for antitumor immune responses. We evaluated whether venetoclax, a selective small-molecule inhibitor of BCL2, would influence the antitumor activity of immune checkpoint inhibitors (ICI). We demonstrate in mouse syngeneic tumor models that venetoclax can augment the antitumor efficacy of ICIs accompanied by the increase of PD-1+ T effector memory cells. Venetoclax did not impair human T-cell function in response to antigen stimuli in vitro and did not antagonize T-cell activation induced by anti–PD-1. Furthermore, we demonstrate that the antiapoptotic family member BCL-XL provides a survival advantage in effector T cells following inhibition of BCL2. Taken together, these data provide evidence that venetoclax should be further explored in combination with ICIs for cancer therapy. Significance: The antiapoptotic oncoprotein BCL2 plays critical roles in tumorigenesis, tumor survival, lymphocyte development, and immune system regulation. Here we demonstrate that venetoclax, the first FDA/European Medicines Agency–approved BCL2 inhibitor, unexpectedly can be combined preclinically with immune checkpoint inhibitors to enhance anticancer immunotherapy, warranting clinical evaluation of these combinations. This article is highlighted in the In This Issue feature, p. 1

OBJECTIVE: Utilizing data obtained from a prospective, international, juvenile systemic sclerosis (SSc) cohort, the present study was undertaken to determine if pulmonary screening with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) is sufficient to assess the presence of interstitial lung disease (ILD) in comparison to high-resolution computed tomography (HRCT) in juvenile SSc. METHODS: The juvenile SSc cohort database was queried for patients enrolled from January 2008 to January 2020 with recorded pulmonary function tests (PFTs) parameters and HRCT to determine the discriminatory properties of PFT parameters, FVC, and DLco in detecting ILD. RESULTS: Eighty-six juvenile SSc patients had both computed tomography imaging and FVC values for direct comparison. Using findings on HRCT as the standard measure of ILD presence, the sensitivity of FVC in detecting ILD in juvenile SSc was only 40%, the specificity was 77%, and area under the curve (AUC) was 0.58. Fifty-eight juvenile SSc patients had both CT imaging and DLco values for comparison. The sensitivity of DLco in detecting ILD was 76%, the specificity was 70%, and AUC was 0.73. CONCLUSION: The performance of PFTs in juvenile SSc to detect underlying ILD was quite limited. Specifically, the FVC, which is one of the main clinical parameters in adult SSc to detect and monitor ILD, would miss ~60% of children who had ILD changes on their accompanying HRCT. The DLco was more sensitive in detecting potential abnormalities on HRCT, but with less specificity than the FVC. These results support the use of HRCT in tandem with PFTs for the screening of ILD in juvenile SSc.

Background: To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods: The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results: A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. Conclusions: We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies. © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Objectives The COVID-19 pandemic is a global health problem. We, as the EMERGE (EMErging RheumatoloGists and rEsearchers) group of PReS (Pediatric Rheumatology European Society) analyzed how the pandemic has affected pediatric rheumatology practice. Methods An online survey was developed to assess changes in pediatric rheumatology practice due to the pandemic. Results were analyzed using descriptive statistics. Results From 70 countries, 493 pediatric rheumatologists (80.3% in pediatric rheumatology practice for ≥5 years) responded to the survey. Around 70% disagreed that the pandemic led to reduced prescription of nonsteroidal anti-inflammatory drugs, conventional synthetic and biologic disease-modifying antirheumatic drugs. Almost half were more likely to taper corticosteroids faster. One-fifth hesitated to switch the major immunosuppressant during a flare. Patients encountering difficulties obtaining hydroxychloroquine and tocilizumab due to shortages were noted by 192 (38.9%) and 44 (8.9%), respectively. Twenty to 30% indicated that their patients had experienced a flare or delay in diagnosis/intervention due to postponed appointments.53% mentioned use of phone calls/smartphone applications while 47% shifted towards video consultations for patient care. Respondents indicated an increased number of patients with Kawasaki disease (30%), macrophage activation syndrome (15.6%), unusual vasculitic rashes (31.4%), and hyperinflammation (33.5%) during the pandemic. Conclusion This is the largest survey to date addressing changes in pediatric rheumatology practice due to the COVID-19 pandemic. Primary changes were due to delays in clinic appointments, increase in use of virtual technologies, and concerns about the use of immunosuppressive therapies. An increased number of patients with Kawasaki disease/hyperinflammation mentioned by the respondents is noteworthy., • COVID-19 pandemic threatens millions of lives worldwide. • As pediatric rheumatologists, we take care of a vulnerable population. • The main changes in pediatric rheumatology practice during the COVID-19 pandemic were due to delays in clinic appointments, increase in use of virtual technologies to decrease in-person visits, use of anti-rheumatic drugs treatment/prophylaxis, and concerns about using immunosuppressive therapies. • An increase in the number of patients with Kawasaki disease/hyperinflammation was also mentioned by the respondents of the survey. • Understanding the challenges imposed by the COVID-19 pandemic on the community of pediatric rheumatologists will help tailor future recommendations regarding the management of pediatric rheumatology patients during the pandemic according to the needs in daily clinical practice.

Survivors of hematopoietic cell transplantation (HCT) have been shown to exhibit both clinical and biological features of accelerated ageing. Most studies used frailty measures, comorbidities for clinical assessment and several biological assessment of premature ageing. However, these tests are less suitable for age determination of individual patients. Recently, DNA methylation has emerged as a novel test to measure cellular age. In the present study, we assessed ageing in a cohort of 26 survivors of allogeneic HCT by frailty tests comprising the handgrip and 6 min walk tests and by biological tests including DNA methylation, telomere length and expression of p16INK4A and serum levels of IL-6. DNA methylation was evaluated both in blood and buccal epithelial cells. Physiological reserve was markedly reduced in transplant survivors, reflected by 6 min walk test. Increased IL-6 serum levels and p16ink4A correlated with accelerated ageing. Overall, the measured age of donor blood cells was significantly higher than these blood cells residing in their respective donors, as reflected by DNA methylation and by buccal epithelium methylation status. These clinical and biological observations suggest that allogeneic HCT is associated with accelerated ageing.

Background Fibrodysplasia ossificans progressiva (FOP) is the most catastrophic form of heterotopic ossification, due to ongoing intracellular signaling through the bone morphogenic protein pathway. The paroxysmal appearance of inflammatory lumps and elevated inflammatory markers during flares, suggest that FOP is an auto-inflammatory disease. Based on evidence, demonstrating a role for interleukin-1β (IL-1β) in other forms of heterotopic ossification, we hypothesized that treating FOP patients with anti-IL-1 agents could help lower the rate of FOP paroxysms and/or limit the symptoms and residual lesions. Case presentation A 13.5-year-old Arab boy was diagnosed with FOP. Treatment with anti-inflammatory drugs did not change the disease course. New lumps appeared in a rate of approximately one every 8 days. Treatment with the anti-IL-1 agents anakinra and canakinumab resulted in significantly lower rate of paroxysms (every 22–25 days, of which almost all involved only 2 existing lumps), as well as shorter duration. High levels of IL-1β were found in the patient’s plasma samples, collected during a paroxysm that appeared 8 weeks after the last canakinumab dose. In contrast, IL-1β plasma levels were undetectable in the previous three plasma samples, obtained while he was treated with anti-IL-1 agents. Conclusions Our data demonstrate the efficacy of anti-IL-1 agents in the treatment of a patient with FOP. Results showing the marked increase in IL-1β plasma levels during a paroxysm support a role for IL-1β in the pathogenesis of FOP and further provide the rationale for the use of anti-IL-1 agents in FOP treatment.

OBJECTIVE To evaluate the association of Jewish cultural and religious identity and denominational affiliation with interest in, intention to undertake and uptake of population-based BRCA (Breast Cancer Gene)-testing. DESIGN Cohort-study set within recruitment to GCaPPS-trial (ISRCTN73338115). SETTING London Ashkenazi-Jewish (AJ) population. POPULATION OR SAMPLE AJ men and women, >18 years. METHODS Participants were self-referred, and attended recruitment clinics (clusters) for pre-test counselling. Subsequently consenting individuals underwent BRCA testing. Participants self-identified to one Jewish denomination: Conservative/Liberal/Reform/Traditional/Orthodox/Unaffiliated. Validated scales measured Jewish Cultural-Identity (JI) and Jewish Religious-identity (JR). Four-item Likert-scales analysed initial 'interest' and 'intention to test' pre-counselling. Item-Response-Theory and graded-response models, modelled responses to JI and JR scales. Ordered/multinomial logistic regression modelling evaluated association of JI-scale, JR-scale and Jewish Denominational affiliation on interest, intention and uptake of BRCA testing. MAIN OUTCOME MEASURES Interest, intention, uptake of BRCA testing. RESULTS In all, 935 AJ women/men of mean age = 53.8 (S.D = 15.02) years, received pre-test education and counselling through 256 recruitment clinic clusters (median cluster size = 3). Denominational affiliations included Conservative/Masorti = 91 (10.2%); Liberal = 82 (9.2%), Reform = 135 (15.1%), Traditional = 212 (23.7%), Orthodox = 239 (26.7%); and Unaffiliated/Non-practising = 135 (15.1%). Overall BRCA testing uptake was 88%. Pre-counselling, 96% expressed interest and 60% intention to test. JI and JR scores were highest for Orthodox, followed by Conservative/Masorti, Traditional, Reform, Liberal and Unaffiliated Jewish denominations. Regression modelling showed no significant association between overall Jewish Cultural or Religious Identity with either interest, intention or uptake of BRCA testing. Interest, intention and uptake of BRCA testing was not significantly associated with denominational affiliation. CONCLUSIONS Jewish religious/cultural identity and denominational affiliation do not appear to influence interest, intention or uptake of population-based BRCA testing. BRCA testing was robust across all Jewish denominations. TWEETABLE ABSTRACT Jewish cultural/religious factors do not affect BRCA testing, with robust uptake seen across all denominational affiliations.

The association of long-term HbA1c variability with mortality has been previously suggested. However, the significance of HbA1c variability and trends in different age and HbA1c categories is unclear.Data on patients with diabetes listed in the Israeli National Diabetes Registry during years 2012-2016 (observation period) were collected. Patients with4 HbA1c measurements, type 1 diabetes, eGFR 30mg/ml/min, persistent HbA1c 6% or malignancy were excluded. Utilizing machine learning methods, patients were classified into clusters according to their HbA1c trend (increasing, stable, decreasing). Mortality risk during 2017-2019 was calculated in subgroups defined by age (35-54, 55-69, 70-89 years) and last HbA1c (≤7% and7%) at end of observation period. Models were adjusted for demographic, clinical and laboratory measurements including HbA1c, standard deviation (SD) of HbA1c and HbA1c trend.This historical cohort study included 293,314 patients. Increased HbA1c variability (high SD) during the observation period was an independent predictor of mortality in patients aged more than 55 years (p 0.01). The HbA1c trend was another independent predictor of mortality. Patients with a decreasing versus stable HbA1c trend had a greater mortality risk; this association persisted in all age groups in patients with HbA1c 7% at the end of the observation period (p = 0.02 in age 35-54; p 0.01 in aged55). Patients with an increasing versus stable HbA1c trend had a greater mortality risk only in the elderly group (70), yet in both HbA1c categories (p 0.01).HbA1c variability and trend are important determinants of mortality risk and should be considered when adjusting glycaemic targets.

In accidental intoxicated animals and humans, Karwinskia humboldtiana (Kh) causes lesions in the central and peripheral nervous system and organs like the kidney, liver, and lung. The objective was to evaluate the histology of myocardium and skeletal muscle after experimental chronic intoxication with mature fruit of Kh in Wistar rat. Twenty-five rats were used and divided into five groups (n = 5): four intoxicated and one control. Kh fruit was ground, dried, sieved, and administered by an orogastric tube. Intoxicated rats received 3.5 g/kg body weight fractionated in 5 doses. Control rats received only water. Animals were euthanized at 24, 48, 58, and 112 days, respectively. Samples of the myocardium and skeletal muscle were obtained and processed for light microscopy evaluation. Morphological analyses were performed, including a microdensitometric analysis. Results showed areas of necrosis in the muscle fibers, fibers with vacuolated cytoplasm, and disorganization of myofilaments, as well as staining variations in both myocardium and skeletal muscle time-depending. Zones with loss of continuity of the external lamina were identified with PAS with the diastase histochemical method. Immunolabeling with specific antibodies demonstrated diminution of actin and desmin myofilaments. The microdensitometric analysis showed a statistically significant difference between the intoxicated vs control group. These findings demonstrate that chronic intoxication of Kh fruit also causes damage in myocardial and skeletal muscle, these alterations will be useful to understand that the toxic effects of Kh fruit in accidently intoxicated humans are systemic, and not only over the nervous system.

Objectives Sleep is necessary for brain function as well as physical and cognitive processes. Sleep disruptions, common with aging, intensify among trauma survivors. Moreover, former prisoners-of-war (ex-POWs) often experience premature aging. This study investigates the longitudinal effects of sleep disruptions for ex-POWs in relation to cognitive performance and telomere length as well as between cognition and telomeres. Method This study included Israeli veterans from the 1973 Yom Kippur War who participated in four assessments (1991, 2003, 2008, 2015): (a) ex-POWs (n = 99), and (b) veterans who not were captured (controls) (n = 101). Among both groups, sleep disruptions were assessed using a self-report item in all four assessments. Cognitive performance was assessed using the Montreal Cognitive Assessment (MOCA) and telomere length was assessed via total white blood cells (leukocytes) from whole blood samples using Southern blot, both were measured only among ex-POWs in 2015. We conducted descriptive statistics, repeated measures, correlations, and path analyses. Results Sleep disruptions were related to lower cognitive performance but not to shorter telomeres. Moreover, cognitive performance and telomere length were found to be related when sleep disruptions were taken into consideration. Conclusion Interpersonal trauma was shown to be a unique experience resulting in sleep disruptions over time, leading to cognitive impairment. These findings highlight the importance of viewing trauma survivors at high-risk for sleep disruptions. Therefore, it is imperative to inquire about sleep and diagnose cognitive disorders to help identify and treat premature aging.

We describe an 11-year-old girl, diagnosed with juvenile polymyositis (JPM), who developed right ureteral obstruction secondary to necrosis. We emphasize the dilemmas regarding optimal timing for surgical intervention and medical treatment. Vascular involvement, which could be a part of juvenile dermatomyositis, may also be a feature of JPM. We discuss the association between vasculopathy and ureteral necrosis and review the literature regarding similar conditions. Whether the ureteral necrosis is a specific feature of vasculopathy, or a result of visceral calcinosis, needs to be further explored.

Background/Aims In March 2020, the WHO characterised COVID-19 as a pandemic. Whilst many people with COVID-19 infection appeared to have mild or no symptoms, a significant proportion became seriously ill. At the time, little was known about how patients with rheumatic or autoimmune conditions, many of whom use immunosuppressive medications, are affected by the virus. The aim of the patient-led longitudinal survey (the COVID-19 European Patient Registry, EPR) is to better understand the impact of COVID-19 on these patients. This specific analysis aims to understand how the number of confirmed COVID-19 cases affects the self-reported level of worry experienced by participants. Methods The EPR comprises an online health questionnaire. Each week participants are sent a short follow-up survey concerning exposure to COVID-19, symptoms, diagnosis, how worried they feel (scale, 0-10), and a range of behaviours. The weekly mean worry score from participants was calculated by country, and compared to the weekly total number of cases of COVID-19 reported within each country. The association between worry score and a range of behaviours was also calculated. Results To 27 September 2020, a total of 3,619 adults and 639 children were included in the EPR. There is a correlation between the total number of weekly cases and the mean worry score amongst UK-based adult participants in the EPR (linear regression, R2=0.779,P Conclusion The number of confirmed cases of COVID-19 is associated with the level of worry, and consequent behaviour change, amongst UK adults with rheumatic conditions. This suggests that the number of cases, government response, and media portrayal affect how worried participants feel. This in turn drives behavioural change towards COVID-avoiding behaviours. This phenomenon appears exclusive to UK-based adults, suggesting differences in the perception of the threat posed by COVID varies between countries. Disclosure R.P. Beesley: None. W. Costello: None. S.P. Angevare: None. Y. Uziel: None. C. Wouters: None. N. Wulffraat: Grants/research support; NW has received funding for research by AbbVie, speakers honorarium by Sobi (not related to this study).

Background/Aims Younger and older people with rheumatic diseases may experience increased anxiety during the COVID-19 pandemic, due to the uncertainty regarding their likelihood of contracting the virus, its complications alongside their existing condition and whether their immunosuppressive treatments pose additional risks. This study explored trajectories of anxiety in parents of children and young people (CYP) with rheumatic diseases and adults with rheumatic diseases in the six months following March 2020 during the COVID-19 pandemic. Methods CYP and adults recruited to the international COVID-19 European Patient Registry, a parent-led, online, self-referred prospective cohort recruiting participants globally, were selected if enrolled within 20th March to 17th April 2020. Anxiety scores (0-10, 10=Highest anxiety) were collected weekly for up to 28 weeks and denoted parent anxiety in the CYP cohort and self-reported anxiety in the adult cohort. Group-based trajectory models explored anxiety clusters using censored-normal models in the CYP and adult populations, separately. Linear, quadratic and cubic polynomials were tested within 1 to 10 clusters and optimal models selected based on a combination of model fit (BIC), parsimony and clinical plausibility. Demographic (country, age, gender) and clinical (diagnosis, disease control, respiratory comorbidity, immunosuppressive therapy) information and COVID-19 mitigation behaviours (isolation, distancing, none) were collected at initial enrolment and compared between clusters using Chi-squared, Fisher’s exact and Kruskal-Wallis tests. Results Among 498 CYP and 2640 adults, most were female (65%, 89%) and from the UK (50%, 84%), respectively. The most common diagnoses were polyarticular JIA (37%) and oligoarticular JIA (29%) among CYP and RA among the adults (63%). Respiratory comorbidities were uncommon in the CYP (10%) and adult (17%) cohorts, and most were taking any immunosuppressive therapies (85%, 87%), respectively. As of March 2020, 88% and 79% were self-isolating, respectively. In both the parents of CYP and adult cohorts, four trajectory clusters were identified with similar patterns: Persistent extremely high anxiety (32%, 17%), persistent high anxiety (43%, 41%), high anxiety that marginally improved (25%, 32%) and moderate anxiety that improved (11%, 10%). Among CYP, few characteristics distinguished the clusters. However, in the adult cohort, clusters with greater and more persistent anxiety were associated with higher levels of respiratory comorbidities, higher use of immunosuppressive therapies, higher initial levels of self-isolation and slightly older age than those with lower or improving anxiety over time. Conclusion This study reports four trajectories of anxiety during the COVID-19 pandemic that are consistent across parents of CYP with rheumatic diseases and among adults with these conditions. Despite relatively lower risks for CYP, parental anxiety regarding COVID-19 was high and not associated with characteristics of their child or of their child's disease. Among adults with rheumatic diseases, greater anxiety was associated with risk factors potentially associated with COVID-19 morbidity and mortality. Disclosure S.J.W. Shoop-Worrall: None. S.M.M. Verstappen: None. W. Costello: None. S.P. Angevare: None. Y. Uziel: None. C. Wouters: None. N. Wulffraat: Honoraria; Sobi. Grants/research support; Abbvie. R. Beesley: None.

Introduction: Cochlear implantation is a recent approach proposed to treat single-sided deafness (SSD) and asymmetric hearing loss (AHL). Several cohort studies showed its effectiveness on tinnitus and variable results on binaural hearing. The main objective of this study is to assess the outcomes of cochlear implantation and other treatment options in SSD/AHL on quality of life. Methods: This prospective multicenter study was conducted in 7 tertiary university hospitals and included an observational cohort study of SSD/AHL adult patients treated using contralateral routing of the signal (CROS) hearing aids or bone-anchored hearing systems (BAHSs) or who declined all treatments, and a randomized controlled trial in subjects treated by cochlear implantation, after failure of CROS and BAHS trials. In total, 155 subjects with SSD or AHL, with or without associated tinnitus, were enrolled. After 2 consecutive trials with CROS hearing aids and BAHSs on headband, all subjects chose any of the 4 treatment options (abstention, CROS, BAHS, or cochlear implant [CI]). The subjects who opted for a CI were randomized between 2 arms (CI vs. initial observation). Six months after the treatment choice, quality of life was assessed using both generic (EuroQoL-5D, EQ-5D) and auditory-specific quality-of-life indices (Nijmegen Cochlear implant Questionnaire [NCIQ] and Visual Analogue Scale [VAS] for tinnitus severity). Performances for speech-in-noise recognition and localization were measured as secondary outcomes. Results: CROS was chosen by 75 subjects, while 51 opted for cochlear implantation, 18 for BAHSs, and 11 for abstention. Six months after treatment, both EQ-5D VAS and auditory-specific quality-of-life indices were significantly better in the “CI” arm versus “observation” arm. The mean effect of the CI was particularly significant in subjects with associated severe tinnitus (mean improvement of 20.7 points ± 19.7 on EQ-5D VAS, 20.4 ± 12.4 on NCIQ, and 51.4 ± 35.4 on tinnitus). No significant effect of the CI was found on binaural hearing results. Before/after comparisons showed that the CROS and BAHS also improved significantly NCIQ scores (for CROS: +7.7, 95% confidence interval [95% CI] = [4.5; 10.8]; for the BAHS: +14.3, 95% CI = [7.9; 20.7]). Conclusion: Cochlear implantation leads to significant improvements in quality of life in SSD and AHL patients, particularly in subjects with associated severe tinnitus, who are thereby the best candidates to an extension of CI indications.

Objective To evaluate the baseline clinical characteristics of juvenile systemic sclerosis (SSc) patients in the international juvenile SSc inception cohort, and to compare these characteristics between the classically defined juvenile diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) subtypes and among those with overlap features. Methods A cross-sectional study was performed using baseline visit data. Information on demographic characteristics, organ system evaluation, treatment, and patient- and physician-reported outcomes was extracted and summary statistics applied. Comparisons between juvenile dcSSc and lcSSc subtypes and patients with and without overlap features were performed using chi-square and Mann-Whitney U tests. Results At data extraction, 150 juvenile SSc patients were enrolled across 42 centers; 83% were White, 80% were female, juvenile dcSSc predominated (72%), and 17% of the cohort had overlap features. Significant differences were found between juvenile dcSSc and juvenile lcSSc regarding modified Rodnan skin thickness score, the presence of Gottron's papules, digital tip ulceration, results of the 6-minute walk test, and composite pulmonary and cardiac involvement. All of these were more frequent in dcSSc except for cardiac involvement. Juvenile dcSSc patients had significantly worse scores for physician-rated disease activity and damage. A significantly higher occurrence of Gottron's papules and musculoskeletal and composite pulmonary involvement, and a significantly lower frequency of Raynaud's phenomenon, were seen in those with overlap features. Conclusion Results from a large international juvenile SSc cohort demonstrate significant differences between juvenile dcSSc and juvenile lcSSc patients, including more globally severe disease and increased frequency of interstitial lung disease in juvenile dcSSc patients, while those with lcSSc have more frequent cardiac involvement. Those with overlap features had an unexpected higher frequency of interstitial lung disease.

We hypothesized that via exosomes, CLL cells turn endothelial cells into “CLL-supportive cells.” To test this hypothesis, we transfected vein-derived (HUVECs) and arterial-derived (HAOEC) endothelial cells with exosomes that we isolated from the peripheral blood of 45 treatment-naive patients. We found that endothelial cells take up CLL exosomes in a dose- and time-dependent manner. Since CLL cells are protected from apoptosis in an IL-6-rich environment, we wondered whether CLL exosomes turn endothelial cells into IL-6-producing cells. To test this, we exposed endothelial cells to CLL exosomes and found a 50% increase in IL-6 levels, suggesting that the endothelial cells exposed to CLL exosomes produced and secreted IL-6. Subsequently, we filtered out this growth medium and added CLL cells to this IL-6-enriched medium. After 15 minutes, STAT3 became phosphorylated, and there was a 40% decrease in the rate of apoptosis among these cells, indicating that IL-6 activated the STAT3-dependent anti-apoptotic pathway. Phosphor-proteomic analysis of endothelial cells that were loaded with CLL exosomes revealed 23 phosphor-proteins that were upregulated. Annotation analysis unraveled the central role of phosphor-β-catenin. To test whether β-catenin enhances the generation of IL-6 in these cells, we transfected HUVECs with a β-catenin-containing plasmid. We found, by ELISA, a 30% increase in the levels of IL-6 in the culture medium, and, by ChIP, the increased binding of 3 transcription factors (NF-κB, LEF/TCF, and C/EBP) to the IL-6 promoter. Taken together, we found that CLL cells communicate with endothelial cells through the exosomes that they release. Once these exosomes are taken up by endothelia, they turn them into IL-6-producing cells.

We show that an overlay (OVL) metrology system based on a scanning electron microscope can achieve accurate registration of buried and resist (top) structures. The positions were determined by both Back Scattered Electrons (BSE) and Secondary Electrons (SE). The accuracy was quantified for After-Development Inspection (ADI) of an advanced EUVL process. Results by linear tracking showed accuracy below 0.4nm, robust across process variation and target designs. The influence of various measurement conditions, e.g. Field of View, on position and OVL tracking was negligible. The measurement methodology presented is applicable for both standalone High Voltage SEM (HV-SEM) registration targets and optical targets, such as the Advanced Imaging Metrology (AIM®) target used by Imaging Based Overlay (IBO) metrology systems. Using SEM ADI OVL results as a calibration for optical overlay metrology tools we can demonstrate significant improvements in the optical ADI OVL accuracy on small targets like AIM in-die (AIMid).

(1) Background: this study aimed to evaluate the worries, anxiety, and depression in the public during the initial coronavirus disease 2019 (COVID-19) pandemic lockdown in three culturally different groups of internet survey respondents: Middle Eastern (Israel), European (Poland), and North American (Canada). (2) Methods: a cross-sectional online survey was conducted in the mentioned countries during the lockdown periods. The survey included a demographic questionnaire, a questionnaire on personal concerns, and the Patient Health Questionnaire-4 (PHQ-4). A total of 2207 people successfully completed the survey. (3) Results: Polish respondents were the most concerned about being infected. Canadian respondents worried the most about their finances, relations with relatives and friends, and both physical and mental health. Polish respondents worried the least about their physical health, and Israeli respondents worried the least about their mental health and relations with relatives and friends. Canadian respondents obtained the highest score in the PHQ-4, while the scores of Israeli respondents were the lowest. (4) Conclusions: various factors should be considered while formulating appropriate solutions in emergency circumstances such as a pandemic. Understanding these factors will aid in the development of strategies to mitigate the adverse effects of stress, social isolation, and uncertainty on the well-being and mental health of culturally different societies.

We describe a miniaturized field-deployable biosensor module, designed to function as an element in a sensor network for standoff monitoring and mapping of environmental hazards. The module harbors live bacterial sensor cells, genetically engineered to emit a bioluminescent signal in the presence of preselected target materials, which act as its core sensing elements. The module, which detects and processes the biological signal, composes a digital record that describes its findings, and can be transmitted to a remote receiver. The module is an autonomous self-contained unit that can function either as a standalone sensor, or as a node in a sensor network. The biosensor module can potentially be used for detecting any target material to which the sensor cells were engineered to respond. The module described herein was constructed to detect the presence of buried landmines underneath its footprint. The demonstrated detection sensitivity was 0.25 mg 2,4-dinitrotoluene per Kg soil.

Dual bromodomain BET inhibitors that bind with similar affinities to the first and second bromodomains across BRD2, BRD3, BRD4, and BRDT have displayed modest activity as monotherapy in clinical trials. Thrombocytopenia, closely followed by symptoms characteristic of gastrointestinal toxicity, have presented as dose-limiting adverse events that may have prevented escalation to higher dose levels required for more robust efficacy. ABBV-744 is a highly selective inhibitor for the second bromodomain of the four BET family proteins. In contrast to the broad antiproliferative activities observed with dual bromodomain BET inhibitors, ABBV-744 displayed significant antiproliferative activities largely although not exclusively in cancer cell lines derived from acute myeloid leukemia and androgen receptor positive prostate cancer. Studies in acute myeloid leukemia xenograft models demonstrated antitumor efficacy for ABBV-744 that was comparable with the pan-BET inhibitor ABBV-075 but with an improved therapeutic index. Enhanced antitumor efficacy was also observed with the combination of ABBV-744 and the BCL-2 inhibitor, venetoclax compared with monotherapies of either agent alone. These results collectively support the clinical evaluation of ABBV-744 in AML (Clinical Trials.gov identifier: NCT03360006).

Accurate lane detection, a crucial enabler for autonomous driving, currently relies on obtaining a large and diverse labeled training dataset. In this work, we explore learning from abundant, randomly generated synthetic data, together with unlabeled or partially labeled target domain data, instead. Randomly generated synthetic data has the advantage of controlled variability in the lane geometry and lighting, but it is limited in terms of photo-realism. This poses the challenge of adapting models learned on the unrealistic synthetic domain to real images. To this end we develop a novel autoencoder-based approach that uses synthetic labels unaligned with particular images for adapting to target domain data. In addition, we explore existing domain adaptation approaches, such as image translation and self-supervision, and adjust them to the lane detection task. We test all approaches in the unsupervised domain adaptation setting in which no target domain labels are available and in the semi-supervised setting in which a small portion of the target images are labeled. In extensive experiments using three different datasets, we demonstrate the possibility to save costly target domain labeling efforts. For example, using our proposed autoencoder approach on the llamas and tuSimple lane datasets, we can almost recover the fully supervised accuracy with only 10% of the labeled data. In addition, our autoencoder approach outperforms all other methods in the semi-supervised domain adaptation scenario.

Objective To build a prediction model for uveitis in children with JIA for use in current clinical practice. Methods Data from the international observational Pharmachild registry were used. Adjusted risk factors as well as predictors for JIA-associated uveitis (JIA-U) were determined using multivariable logistic regression models. The prediction model was selected based on the Akaike information criterion. Bootstrap resampling was used to adjust the final prediction model for optimism. Results JIA-U occurred in 1102 of 5529 JIA patients (19.9%). The majority of patients that developed JIA-U were female (74.1%), ANA positive (66.0%) and had oligoarthritis (59.9%). JIA-U was rarely seen in patients with systemic arthritis (0.5%) and RF positive polyarthritis (0.2%). Independent risk factors for JIA-U were ANA positivity [odds ratio (OR): 1.88 (95% CI: 1.54, 2.30)] and HLA-B27 positivity [OR: 1.48 (95% CI: 1.12, 1.95)] while older age at JIA onset was an independent protective factor [OR: 0.84 (9%% CI: 0.81, 0.87)]. On multivariable analysis, the combination of age at JIA onset [OR: 0.84 (95% CI: 0.82, 0.86)], JIA category and ANA positivity [OR: 2.02 (95% CI: 1.73, 2.36)] had the highest discriminative power among the prediction models considered (optimism-adjusted area under the receiver operating characteristic curve = 0.75). Conclusion We developed an easy to read model for individual patients with JIA to inform patients/parents on the probability of developing uveitis.

ObjectivesTo describe the clinical characteristics, treatment response and genetic findings in a large cohort of patients with undefined systemic autoinflammatory diseases (SAIDs).MethodsClinical and genetic data from patients with undefined SAIDs were extracted from the Eurofever registry, an international web-based registry that retrospectively collects clinical information on patients with autoinflammatory diseases.ResultsThis study included 187 patients. Seven patients had a chronic disease course, 180 patients had a recurrent disease course. The median age at disease onset was 4.3 years. Patients had a median of 12 episodes per year, with a median duration of 4 days. Most commonly reported symptoms were arthralgia (n=113), myalgia (n=86), abdominal pain (n=89), fatigue (n=111), malaise (n=104) and mucocutaneous manifestations (n=128). In 24 patients, relatives were affected as well. In 15 patients, genetic variants were found in autoinflammatory genes. Patients with genetic variants more often had affected relatives compared with patients without genetic variants (p=0.005). Most patients responded well to non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, colchicine and anakinra. Complete remission was rarely achieved with NSAIDs alone. Notable patterns were found in patients with distinctive symptoms. Patients with pericarditis (n=11) were older at disease onset (33.8 years) and had fewer episodes per year (3.0/year) compared with other patients. Patients with an intellectual impairment (n=8) were younger at disease onset (2.2 years) and often had relatives affected (28.6%).ConclusionThis study describes the clinical characteristics of a large cohort of patients with undefined SAIDs. Among these, patients with pericarditis and intellectual impairment appear to comprise distinct subsets.

Made available in DSpace on 2019-10-05T16:54:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-04-01 IRCCS Istituto Giannina Gaslini Background To our knowledge, the characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate, with a cross-sectional study, the prevalence of disease categories, treatment methods, and disease status in patients from across different geographical areas and from countries with diverse wealth status. Methods In this multinational, cross-sectional, observational cohort study, we asked international paediatric rheumatologists from specialised centres to enrol children with a diagnosis of juvenile idiopathic arthritis, according to International League of Associations for Rheumatology criteria, who were seen consecutively for a period of 6 months. Each patient underwent retrospective and cross-sectional assessments, including measures of disease activity and damage and questionnaires on the wellbeing and quality of life of the children. We qualitatively compared the collected data across eight geographical areas, and we explored an association between disease activity and damage and a country's gross domestic product (GDP) with a multiple logistic regression analysis. Findings Between April 4, 2011, and Nov 21, 2016, 9081 patients were enrolled at 130 centres in 49 countries, grouped into eight geographical areas. Systemic arthritis (125 [33.0%] of 379 patients) and enthesitis-related arthritis (113 [29.8%] of 379) were more common in southeast Asia, whereas oligoarthritis was more prevalent in southern Europe (1360 [56.7%] of 2400) and rheumatoid factor-negative polyarthritis was more frequent in North America (165 [31.5%] of 523) than in the other areas. Prevalence of uveitis was highest in northern Europe (161 [19.1%] of 845 patients) and southern Europe (450 [18.8%] of 2400) and lowest in Latin America (54 [6.4%] of 849), Africa and Middle East (71 [5.9%] of 1209), and southeast Asia (19 [5.0%] of 379). Median age at disease onset was lower in southern Europe (3.5 years, IQR 1.9-7.3) than in other regions. Biological, disease-modifying antirheumatic drugs were prescribed more frequently in northern Europe and North America than in other geographical settings. Patients living in countries with lower GDP had greater disease activity and damage than those living in wealthier countries. Damage was associated with referral delay. Interpretation Our study documents a variability in prevalence of disease phenotypes and disparities in therapeutic choices and outcomes across geographical areas and wealth status of countries. The greater disease burden in lowerresource settings highlights the need for public health efforts aimed at improving equity in access to effective treatments and care for juvenile idiopathic arthritis. Copyright (C) 2019 Elsevier Ltd. All rights reserved. Univ Genoa, Ist Giannina Gaslini, IRCCS, Clin Paediat & Rheumatol, Genoa, Italy Univ Genoa, Ist Giannina Gaslini, IRCCS, Epidemiol & Biostat Serv, Genoa, Italy Univ Genoa, Ist Giannina Gaslini, IRCCS, Sci Directory, Genoa, Italy Univ Genoa, PRINTO, IRCCS, Ist Giannina Gaslini, Genoa, Italy Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet & Maternal, Genoa, Italy Wilhelmina Childrens Hosp, Dept Pediat Immunol & Rheumatol, Utrecht, Netherlands Sanjay Gandhi Postgrad Inst Med Sci, Lucknow, Uttar Pradesh, India Univ Hosp 12 Octubre, Dept Pediat Rheumatol, Madrid, Spain Alfaisal Univ, Dept Pediat Rheumatol, King Faisal Specialist Hosp, Riyadh, Saudi Arabia Alfaisal Univ, Res Ctr, Riyadh, Saudi Arabia Western Univ Childrens Hosp, Hlth Sci Ctr, London, ON, Canada Oslo Univ Hosp, Dept Rheumatol, Oslo, Norway Oslo Univ Hosp, Med Fac, Oslo, Norway Univ Oslo, Oslo, Norway Oslo Univ Hosp, Norwegian Natl Advisory Unit Rheumat Dis Children, Oslo, Norway Univ Hosp Munster, Dept Pediat Rheumatol & Immunol, Munster, Germany Hosp Sor Maria Ludovica, Rheumatol Serv, La Plata, Buenos Aires, Argentina Bucharest Emergency Hosp, Cluj Napoca, Romania Childrens Emergency Hosp, Cluj Napoca, Romania Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA Alberta Childrens Prov Gen Hosp, Div Pediat Rheumatol, Dept Pediat, Calgary, AB, Canada Sofiamed, Pediat Dept, Sofia, Bulgaria Rigshosp, Juliane Marie Ctr, Paediat Rheumatol Unit, Copenhagen, Denmark Natl Inst Rheumatism & Physiotherapy, Clin Immunol Adult & Paediat Rheumatol Dept, Budapest, Hungary Univ Latvia, Pediat Dept, Riga, Latvia Univ Latvia, Univ Childrens Hosp, Riga, Latvia Univ Estadual Paulista, Botucatu Fac Med, Botucatu, SP, Brazil Shariati Hosp, Rheumatol Res Ctr, Dept Pediat & Rheumatol, Tehran, Iran Inst Rheumatol Belgrade, Div Pediat Rheumatol, Belgrade, Serbia Thessaloniki Univ, Dept Pediat 1, Hippokrat Gen Hosp, Sch Med, Thessaloniki, Greece Univ Estadual Paulista, Botucatu Fac Med, Botucatu, SP, Brazil

Objectives: To describe the treatment choice in a cohort of subjects with single-sided deafness (SSD) and asymmetric hearing loss (AHL). To assess the reliability of the treatment trials. Design: In this national, multicentre, prospective study, the choice of subjects was made after two consecutive trials of Contralateral Routing Of the Signal (CROS) hearing aids and a Bone Conduction Device (BCD) on a headband. Subjects could proceed with one of these two options, opt for cochlear implantation or decline all treatments. Setting: Seven tertiary university hospitals. Participants: One hundred fifty-five subjects with SSD or AHL fulfilling the candidacy criteria for cochlear implantation, with or without associated tinnitus. Main outcome measures: After the two trials, the number of subjects choosing each option was described. Repeated assessments of both generic and auditory-specific quality of life were conducted, as well as hearing assessments (speech recognition in noise and horizontal localization). Results: CROS was chosen by 75 subjects, followed by cochlear implantation (n = 51), BCD (n = 18) and abstention (n = 11). Patients who opted for cochlear implantation had a poorer quality of life (P = .03). The improvement of quality of life indices after each trial was significantly associated with the final treatment choice (P = .008 for generic indices, P = .002 for auditory-specific indices). The follow-up showed that this improvement had been overestimated in the CROS group, with a long-term retention rate of 52.5%. Conclusions: More than one third of SSD/AHL subjects are unsatisfied after CROS and BCD trials. Repeated quality of life assessments help counselling the patient for his/her treatment choice.

Photo-realistic visualization and animation of expressive human faces have been a long standing challenge. 3D face modeling methods provide parametric control but generates unrealistic images, on the other hand, generative 2D models like GANs (Generative Adversarial Networks) output photo-realistic face images, but lack explicit control. Recent methods gain partial control, either by attempting to disentangle different factors in an unsupervised manner, or by adding control post hoc to a pre-trained model. Unconditional GANs, however, may entangle factors that are hard to undo later. We condition our generative model on pre-defined control parameters to encourage disentanglement in the generation process. Specifically, we condition StyleGAN2 on FLAME, a generative 3D face model. While conditioning on FLAME parameters yields unsatisfactory results, we find that conditioning on rendered FLAME geometry and photometric details works well. This gives us a generative 2D face model named GIF (Generative Interpretable Faces) that offers FLAME's parametric control. Here, interpretable refers to the semantic meaning of different parameters. Given FLAME parameters for shape, pose, expressions, parameters for appearance, lighting, and an additional style vector, GIF outputs photo-realistic face images. We perform an AMT based perceptual study to quantitatively and qualitatively evaluate how well GIF follows its conditioning. The code, data, and trained model are publicly available for research purposes at http://gif.is.tue.mpg.de., International Conference on 3D Vision (3DV) 2020

Objectives In health care, empathy is associated with compassion, thoughtfulness, attentiveness and caring. While empathy is perceived as desirable and positive, it can potentially be associated with negative aspects, such as secondary traumatic stress or vicarious trauma (VT). VT addresses the secondary vicarious influences of patients' pain and discomfort on clinicians. Dentists are routinely exposed to patients' anxiety, pain and discomfort. These may lead to VT, which in turn can affect empathy. The objectives of the present study were to examine the existence of VT among dentists and its association with their empathic approach. Materials and methods Two-hundred and fifty dentists were approached personally and by mail, and asked to complete: (i) the Jefferson Scale of Physician Empathy - Health Professionals; (ii) the Vicarious Trauma Scale; and (iii) demographic, personal and professional data, including age, definition of professional speciality, number of working hours per week and number of sleeping hours per night. Results A total of 200 dentists responded (80% response rate). No differences were found between genders regarding empathy or VT. Dentists who have been accredited as a specialist in one of the dental fields (dental specialists) presented higher empathy scores than general practitioners. VT correlated positively with number of working hours per week and negatively with empathy. The best predictor of empathy was number of sleeping hours per night, followed by VT and age. Conclusions Empathy in the clinical setting is closely associated with secondary VT among dentists. Decreasing dentists' VT may benefit dentists' empathy and through this lead to better clinical outcomes.

Background: In late December 2019, a new pandemic caused by the SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection began to spread around the world. The new situation gave rise to severe health threats, economic uncertainty, and social isolation, causing potential deleterious effects on people&rsquo, s physical and mental health. These effects are capable of influencing oral and maxillofacial conditions, such as temporomandibular disorders (TMD) and bruxism, which could further aggravate the orofacial pain. Two concomitant studies aimed to evaluate the effect of the current pandemic on the possible prevalence and worsening of TMD and bruxism symptoms among subjects selected from two culturally different countries: Israel and Poland. Materials and Methods: Studies were conducted as cross-sectional online surveys using similar anonymous questionnaires during the lockdown practiced in both countries. The authors obtained 700 complete responses from Israel and 1092 from Poland. In the first step, data concerning TMDs and bruxism were compared between the two countries. In the second step, univariate analyses (Chi2) were performed to investigate the effects of anxiety, depression, and personal concerns of the Coronavirus pandemic, on the symptoms of TMD, and bruxism symptoms and their possible aggravation. Finally, multivariate analyses (logistic regression models) were carried out to identify the study variables that had a predictive value on TMD, bruxism, and symptom aggravation in the two countries. Results: The results showed that the Coronavirus pandemic has caused significant adverse effects on the psychoemotional status of both Israeli and Polish populations, resulting in the intensification of their bruxism and TMD symptoms. Conclusions: The aggravation of the psychoemotional status caused by the Coronavirus pandemic can result in bruxism and TMD symptoms intensification and thus lead to increased orofacial pain.

This study concerns the results of cochlear implantation in children and adults from French cochlear implantation centers, monitored at one, two and three years by the Cochlear Implant French Registry EPIIC. This multicenter study enrolled 2603 subjects (1667 adults and 936 children) implanted in one ear. The following parameters were studied: hearing overall performances, monosyllabic or dissyllabic word perception, speech intelligibility, self-assessment questionnaire of Cochlear Implant (CI) benefits (Abbreviated profile of Hearing aid Benefit); professional activity and schooling. This study confirms the ceiling effect in adults’ performances after the 1st year and the progressive growth in children's performances. It also shows that the contralateral hearing aid enhances performances compared to the CI alone condition, in all follow-up sessions. The French register of CIs is the only worldwide register of systematic follow-up on a period of three years and more of all adults and children implanted in a country. 137;Supplement 1

Background To determine if a modified ovarian sensitivity index (MOSI), based on initial follicular measurements and the initial follicle-stimulating hormone (FSH) dose, can predict the production of high-quality embryos for successful implantation during in vitro fertilization (IVF). Methods This study consisted of two phases: 1) a retrospective study and 2) a prospective observational study. For the first phase, 363 patients charts were reviewed, of which 283 had embryos transferred. All women underwent a standardized antagonist-based IVF protocol. At the first follow-up (Day 3/4), the number and size of the follicles were determined. MOSI was calculated as ln (number follicles (≥6 mm) × 1000 / FSH initial dose). Afterward, the number and quality of the ova, embryo development, and the number and quality of the blastocysts were determined. Embryo implantation was confirmed by β-hCG. For the second phase, 337 IVF cycles were followed to determine MOSI’s accuracy. Results MOSI could predict the production of ≥4 high-quality embryos by Day 2 (AUC = 0.69, 95%CI:0.63–0.75), ≥2 blastocysts (AUC = 0.74, 95%CI:0.68–0.79), and ≥ 35% rate of blastocyst formation (AUC = 0.65, 95%CI:0.58–0.72). Using linear regression, MOSI was highly associated with the number of ova captured (β = 5.15), MII oocytes (β = 4.31), embryos produced (β = 2.90), high-quality embryos (β = 0.98), and the blastocyst formation rate (β = 0.06, p Conclusion MOSI was highly correlated with key IVF parameters that are associated with achieved pregnancy. Using this index with antagonist cycles, clinicians may opt to stop an IVF cycle, under the assumption that the cycle will fail to produce good blastocysts, preventing wasting the patient’s resources and time.

Chronic pain induces a multitude of harmful effects; recently it has been suggested that chronic pain is also associated with premature aging, manifested in shortened telomere length (TL). However, evidence for this hypothesis is scarce and inconsistent. The aim was twofold: 1) Investigate whether chronic pain is associated with premature aging, and 2) Determine whether physical exercise (PE) moderates this association if it exists. Participants were 116 male subjects, with (n = 67) and without chronic pain (n = 49). Blood samples for TL analysis were collected and participants were interviewed and completed questionnaires. As a part of the cohort, we included people with physical disability; this variable was controlled in the analysis. The TL of individuals with chronic pain was significantly shorter than that of pain-free individuals. Regression analysis revealed a significant moderating effect of PE on chronic pain and TL, above and beyond the effects of disability, age, and weight. Whereas chronic pain was associated with shorter telomeres in participants who did not exercise, this association was nonsignificant among participants who did exercise. The results suggest that chronic pain is associated with premature ageing; however, PE may mitigate this association and may protect individuals against the harmful effects of chronic pain. Perspective The study suggests that it is important to monitor signs of premature ageing among chronic pain patients as they are at risk. However, chronic pain patients may benefit from regular PE in this respect as it may moderate premature ageing.

Several biologic drugs are available for treatment of immune-mediated diseases, and the number of children treated with biologics is increasing. This review summarises current knowledge about the safety and immunogenicity of vaccines in children treated with biologic therapy. A recent retrospective, multicentre study reported that the booster dose of live-attenuated vaccine (MMR/V) was safe for patients with rheumatic diseases treated with biologic therapy. Recent publications revealed that immunogenicity of vaccines in children treated with biologics was lower than in the healthy population, especially on long-term follow-up. Children treated with biologic therapy are at greater danger of infections, compared to the healthy population. Therefore, they should be vaccinated according to national guidelines. Regardless of the therapy, non-live vaccines are recommended. However, it is common practice to advise postponing vaccination with live-attenuated vaccines in children while they are on immunosuppressive therapy. Newly published data suggest that booster dose MMR/V is safe for children treated with biologic therapy.

ObjectiveTo estimate the prevalence of Joubert syndrome (JS) in Italy applying standards of descriptive epidemiology and to provide a molecular characterization of the described patient cohort.MethodsWe enrolled all patients with a neuroradiologically confirmed diagnosis of JS who resided in Italy in 2018 and calculated age and sex prevalence, assuming a Poisson distribution. We also investigated the correlation between proband chronological age and age at diagnosis and performed next-generation sequencing (NGS) analysis on probands' DNA when available.ResultsWe identified 284 patients with JS: the overall, female- and male-specific population-based prevalence rates were 0.47 (95% confidence interval [CI] 0.41–0.53), 0.41 (95% CI 0.32–0.49), and 0.53 (95% CI 0.45–0.61) per 100,000 population, respectively. When we considered only patients in the age range from 0 to 19 years, the corresponding population-based prevalence rates rose to 1.7 (95% CI 1.49–1.97), 1.62 (95% CI 1.31–1.99), and 1.80 (95% CI 1.49–2.18) per 100,000 population. NGS analysis allowed identifying the genetic cause in 131 of 219 screened probands. Age at diagnosis was available for 223 probands, with a mean of 6.67 ± 8.10 years, and showed a statistically significant linear relationship with chronological age (r2 = 0.79; p < 0.001).ConclusionsWe estimated for the first time the age and sex prevalence of JS in Italy and investigated the patients’ genetic profile. The obtained population-based prevalence rate was ≈10 times higher than that available in literature for children population.

Online social networks (OSNs) are ubiquitous attracting millions of users all over the world. Being a popular communication media OSNs are exploited in a variety of cyber attacks. In this article, we discuss the Chameleon attack technique, a new type of OSN-based trickery where malicious posts and profiles change the way they are displayed to OSN users to conceal themselves before the attack or avoid detection. Using this technique, adversaries can, for example, avoid censorship by concealing true content when it is about to be inspected; acquire social capital to promote new content while piggybacking a trending one; cause embarrassment and serious reputation damage by tricking a victim to like, retweet, or comment a message that he wouldn't normally do without any indication for the trickery within the OSN. An experiment performed with closed Facebook groups of sports fans shows that (1) Chameleon pages can pass by the moderation filters by changing the way their posts are displayed and (2) moderators do not distinguish between regular and Chameleon pages. We list the OSN weaknesses that facilitate the Chameleon attack and propose a set of mitigation guidelines.

International audience; Epithelial ovarian cancers are insidious pathologies that give a poor prognosis due to their late discovery and the increasing emergence of chemoresistance. Development of small pharmacological anticancer molecules remains a major challenge. Ribavirin, usually used in the treatment of hepatitis C virus infections and more recently few cancers, has been a suggestion. However, Ribavirin has many side-effects, suggesting that the synthesis of analogs might be more appropriate. We have investigated the effect of a Ribavirin analog, SRO-91, on cancer cell behavioral characteristics considered as some of the hallmarks of cancer. Two human ovarian adenocarcinoma cell lines (SKOV3 and IGROV1) and normal cells (mesothelial and fibroblasts) have been used to compare the effects of SRO-91 with those of Ribavirin on cell behavior underlying tumor cell dissemination. SRO-91, like Ribavirin, inhibits proliferation, migration, clonogenicity and spheroids formation of cancer cells. Unlike Ribavirin, SRO-91 is preferentially toxic to cancer compared with normal cells. An in vitro physiologically relevant model showed that SRO-91, like Ribavirin or cisplatin, inhibits cancer cell implantation onto peritoneal mesothelium. In conclusion, SRO-91 analog effects on tumor dissemination and its safety regarding non-cancerous (normal) cells are encouraging findings a promising drug for the treatment of ovarian cancer.

This paper presents a visual saliency algorithm for fast object detection and recognition in mobile robots using low power graphics processing units (GPUs), based on human vision foveation. The step of image foveation enables the use of small images, which leads to a much reduced number of computations in deep convolutional neural networks and consequent increase in frame-rate. We demonstrate how using a simple foveated downsampling method, we can maintain a detection-recognition performance level similar to the level at larger image resolutions, even when transforming from 416×416 to 128×128 pixels, for a small high acuity region of the image, which can lead to a 4× speed up in frame rates, maintaining a relatively stable mean Average Precision. The visual saliency algorithm is evaluated on the Stanford drone dataset and our own experimental drone dataset.

Introduction: Juvenile systemic sclerosis is an orphan disease. Currently, the majority of juvenile systemic sclerosis cohort studies are retrospective in design without standardized assessment. This study was conducted prospectively to investigate the difference in manifestations of limited cutaneous juvenile systemic sclerosis and diffuse cutaneous juvenile systemic sclerosis subtypes. An additional aim was to compare these data to other juvenile systemic sclerosis cohorts and a large adult systemic sclerosis cohort. Methods: Patients fulfilling the Paediatric Rheumatology European Society juvenile systemic sclerosis classification criteria were included. Clinical characteristics and patient-related outcomes were assessed. Results: In all, 88 patients with a mean disease duration of 3.5 years were enrolled, 72.5% with diffuse cutaneous juvenile systemic sclerosis with a mean modified Rodnan Skin score of 18 and 27.5% with limited cutaneous juvenile systemic sclerosis with mean modified Rodnan Skin score of 9. The mean age at the onset of Raynaud’s and first non-Raynaud’s symptoms was similar in both groups, approximately 9 and 10.5 years. Active digital tip ulcerations were present in 29% diffuse cutaneous juvenile systemic sclerosis and none in the limited cutaneous juvenile systemic sclerosis subjects (p = 0.005). Of those with cardiopulmonary testing, 3% of diffuse cutaneous juvenile systemic sclerosis and 23% of limited cutaneous juvenile systemic sclerosis group had cardiac involvement (p = 0.015), and 41% diffuse cutaneous juvenile systemic sclerosis and 22% of the limited cutaneous juvenile systemic sclerosis group had pulmonary involvement (p = 0.009). Physician global disease damage assessment was higher in the diffuse cutaneous juvenile systemic sclerosis group compared to the limited cutaneous juvenile systemic sclerosis group: 35 and 15 (p = 0.021). Discussion: The majority of this international juvenile systemic sclerosis cohort had diffuse cutaneous juvenile systemic sclerosis (72.5%) with more frequent vascular and pulmonary involvement compared to the limited cutaneous group, who had increased cardiac involvement. Our cohort reflects prior findings of published juvenile systemic sclerosis cohorts and emphasizes a difference in the presentation compared to adult-onset systemic sclerosis.

Objectives Data on the outcome of stage IIA1 cervical cancer is limited, as these tumors comprise a small percentage of early tumors. NCCN guidelines suggest consideration of surgical management for small tumors with vaginal involvement. Our objective was to evaluate the risk of adjuvant radiotherapy in stage IIA1 cervical cancer and its associated features, in order to improve selection of patients for surgical management. Methods A retrospective cohort study comparing surgically treated cervical cancer patients with stage IB1 and stage IIA1 disease. Women treated between 2000 and 2015 in ten Israeli medical centers were included. Patient and disease features were compared between stages. The relative risk (Fisher's exact test) of receiving post-operative radiation was calculated and compared for each risk factor. A general linear model (GLM) was used for multivariable analysis. Results 199 patients were included, of whom 21 had stage IIA1 disease. Most features were comparable for stage IB1 and stage IIA1 disease, although patients with vaginal involvement were more likely to have close surgical margins (23.8% vs 8.5%, p = 0.03). Patients with stage IIA1 disease were more likely to receive radiation after surgery (76% vs. 46%, RR = 1.65 (1.24–2.2), p = 0.011). Vaginal involvement as well as depth of stromal invasion, LVSI and lymph node metastases were independent predictors of radiation on multivariable general linear modeling. Conclusions Cervical cancer patients with vaginal involvement are highly more likely to require postoperative radiation. We recommend careful evaluation of these patients before surgical management is offered.

Purpose The purpose of this paper is to analyze contemporary uses and gratifications (U&G) of the media, focusing on the differences between emergency and ordinary times, and between media consumers in the border region and in the home front during the Israel-Gaza War (2014). Design/methodology/approach The study used a questionnaire containing 184 items. This significant number of items was necessary due to the large number of media channels and potential uses examined. Due to the length of the questionnaire, and the inclusion of individuals who are not habitual internet users, data were collected in the field rather than through a telephone survey or online. The list of media and uses was compiled based on a review of existing literature regarding functions of media in emergencies. Findings Television and news websites are dominant suppliers of national and local information, but mobile and social channels lead in terms of social uses, discussions, requests and provision of assistance. The same channels were almost always used during emergencies and ordinary times to satisfy a specific need. The leading channels – television, Facebook, WhatsApp and SMS – were used significantly more on the frontlines than on the home front. The findings demonstrate that people use diverse media, but channels that are live, visual, social and mobile are dominant. Originality/value Very few academic studies have compared media uses during ordinary times and emergencies, and those existing focus on the uses of a specific medium. The present study examines various U&G of traditional and new media during the war, compares uses during the war with uses during ordinary times, and compares the population in the border region with the population in the home front.

There is at present no consensus on the treatment of obstructive Eustachian tube dysfunction. In case of failure of well-conducted drug and pressure therapy, some authors recommend balloon dilation; the present study aimed to assess the efficacy and safety of Eustachian tube balloon dilation. Materials and methods A single-center retrospective study assessed clinical and tubomanometric results of Eustachian tube balloon dilation, complications and satisfaction in a consecutive series managed between June 2012 and February 2015. Indications were based on clinical and paraclinical signs of obstructive tube dysfunction despite well-conducted medical treatment. Results Forty-five procedures were performed in 38 patients. Improvement in clinical symptoms was assessed as 88%, 80% and 80% at respectively 2 months, 6 months, and > 1 year. Improved function on tubomanometry was observed in 81% of cases. The procedure was well tolerated, with a minor complications rate of only 4%. Conclusions The present findings for efficacy, tolerance and safety were comparable to those in the literature, despite first-line failure in all patients. Eustachian tube function normalized in about one-third of cases. Despite these encouraging results, true efficacy remains to be confirmed in prospective studies with higher levels of evidence.

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Hebrew language. The reading comprehension of the questionnaire was tested in ten JIA parents and patients. Each participating centre was asked to collect demographic, clinical data, and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, and construct validity (convergent and discriminant validity). A total of 116 JIA patients (17.2% systemic, 56% oligoarticular, 20.7% RF negative poly-arthritis, and 6.1% other categories) and 98 healthy children were enrolled in two centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Hebrew version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and in clinical research.

A anemia ferropriva é um problema de saúde global originado por um longo período de déficit entre a quantidade de ferro biologicamente disponível no organismo e a sua necessidade orgânica, reduzindo no número de hemoglobina e a capacidade de transporte de oxigênio feito por esta proteína. Nesse contexto o objetivo geral desse projeto é observar os aspectos epidemiológicos de anemia ferropriva em populações indígenas rurais e urbanas do Brasil. Tendo como objetivos específicos: Descrever a prevalência da anemia ferropriva nessa população; avaliar a incidência da anemia na população indígena; comparar os dados epidemiológicos nas diferentes regiões e etnias no Brasil. Para tanto, será desenvolvido um estudo de revisão integrativa da literatura, com procedimento descritivo e comparativo, utilizando como fonte de dados a bibliografia da anemia ferropriva em populações indígenas no Brasil. O estudo será conduzido por meio da seleção de estudos nos bancos de dados: Google Acadêmico, Scielo – Scientific Electronic Library Online, Lilacs – Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde e Pubmed – U. S. National Library of Medicine seguindo uma estratégia de busca conforme os descritores: “Anemia Ferropriva”, “Epidemiologia”, “Indígenas”, “Brasil”, “População indígena” e “Anemia por deficiência de ferro”, tendo como universo de tempo de 10 anos (2011-2021).

Background and Objectives: Nutritional deficiencies are one of the main triggers for the development of gastrointestinal diseases, such as ulcerative colitis (UC). Therefore, the objective of the present work consisted of determining the nutrients present in the bone broth (BB) and evaluating their anti-inflammatory properties in a murine model of UC, induced by intrarectal administration of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS), and acetic acid (AcOH). The BB was prepared from the femur of bovine cattle and cooked in distilled water for 8 h at 100 ± 2 °C. Materials and Methods: The BB was administered ad libitum to BALB/c mice for 10 days before the induction of UC. Colon samples were collected for histological analysis and determination of cytokine expression levels by qPCR. Results: It was found that amino acids (AA) are the main nutritional contribution of BB, 54.56% of these correspond to essential AA. The prophylactic administration of BB in the murine model of UC reduced histological damage, decreased the expression of IL-1β (61.12%), IL-6 (94.70%), and TNF-α (68.88%), and increased the expression of INF-γ (177.06%), IL-4 (541.36%), and IL-10 (531.97%). Conclusions: This study shows that BB has anti-inflammatory properties, and its consumption can decrease the symptoms of UC.