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BackgroundOver 90% of patients with systemic sclerosis (SSc) experience Raynaud’s phenomenon (RP), which strongly influences quality of life. Therapeutic options of RP include drug treatment and general lifestyle measures such as smoking cessation and avoiding cold by wearing warm clothes and gloves including electrically heated gloves or silver fiber gloves. Clinical observations suggest an additional benefit of silver fiber gloves compared to normal gloves. Silver is thought to help by reflecting heat back into the hands allowing less heat to escape and has an antimicrobial effect. Despite its generalized use among SSc patients, no objective evidence regarding its superiority for RP over normal gloves exists.ObjectivesTo evaluate the added value of 8% silver fiber gloves compared to normal gloves in the treatment of patients with RP secondary to SSc.MethodsThis was a multicenter double-blind randomized cross-over trial in which 85 SSc patients were randomized in two sequences: 8% silver fiber gloves in period 1 and normal gloves in period 2 or vice versa; each period lasted six weeks. To reduce bias of interindividual differences and external factors (e.g. temperature), a cross-over design was performed in the Netherlands during the winter months. The primary outcome was the triweekly Raynaud Condition Score (RCS), a scale from 1 (no symptoms) to 10 (extreme symptoms). A linear mixed model was used with RCS as dependent and type of gloves as independent variable, adjusted for baseline RCS. Secondary outcome measures included number of RP attacks, RP attack duration, Health Assessment Questionnaire (HAQ-DI) and vascular complications. Secondary outcomes were also analyzed with linear mixed models. All analyses were performed and interpreted before unblinding.ResultsThe 85 included SSc patients had a mean age of 60 (SD:12), 80% were female, 60% had limited cutaneous SSc and 67% used vasoactive medication. Ten patients prematurely ended the study due to various reasons, most notable: allergic reaction to gloves (n=2). At baseline, mean RCS was 6.43 (SD 1.6), with silver fiber gloves the mean RCS decreased to 3.91 (SD 2.3) and with normal gloves to 3.90 (SD 2.3) (Figure 1). No statistically significant difference in RCS during follow-up was observed between the silver fiber gloves and normal gloves (β 0.067, 95% CI -0.006 to 0.19), meaning that on the 1-10 scale, silver fibre gloves gave only a 0.067 higher RCS compared to normal gloves (Table 1). For all other secondary outcome measures, we did not find a statistically significant difference between silver fiber gloves and normal gloves, except for the HAQ (β 0.036, 95% CI 0.026 to 0.046; Table 1), which is not clinically relevant. One vascular complication occurred in the silver fiber gloves, compared to three vascular in the normal gloves, which was not statistically significant different (OR:3.2, 95% CI 0.32 to 31.1).Table 1.Primary and secondary efficacy outcomesβ95% confidence intervalPrimary outcomeRaynaud Condition Score0.067-0.0059; 0.194Secondary outcomesRaynaud attacks frequency-0.480-1.215; 0.255Raynaud attacks duration39.80-36.051; 115.654VAS warmth hands-0.086-0.212; 0.041Impact Raynaud0.088-0.035; 0.211HAQ_DI0.0360.026; 0.046VAS: visual analogue scale; HAQ: Health Assessment QuestionnaireThe reference category was Normal gloves.Linear mixed models were performed with the primary and secondary outcomes as dependent variables, the type of gloves as independent variable, adjusted for baseline Raynaud Condition Score.Figure 1.Raynaud Condition Score during the study periodConclusionThis trial shows that wearing any type of glove decreases the RP burden in SSc patients, but no additional benefit from gloves containing 8% silver fibers compared to normal gloves could be demonstrated. Potentially, less vascular complications may arise in SSc patients wearing silver fiber gloves. Further confirmation of this potential benefit is necessary.AcknowledgementsThe authors would like to thank all participants of this study and Skafit for providing the gloves.Disclosure of InterestsNone declared

The childhood immunization schedule is well known and generally well implemented in developed countries. For various reasons, the same is not true of vaccines aimed at preventing infections in adults, in which vaccination coverage is incomplete and generally very deficient. In order to assess the situation of adult vaccination in Spain, the Fundación de Ciencias de la Salud has brought together a series of experts in different fields, including doctors, nurses, representatives of patient associations, health managers and economists, health authorities and journalists to deal with this issue. The format was that of a round table in which a series of questions previously formulated by the coordinators were to be answered and debated. The document presented is not an exhaustive review of the topic, nor is it intended to make recommendations, but only to give a multidisciplinary opinion on topics that could be particularly debatable or controversial. The paper reviews the main vaccine-preventable adult diseases, their clinical and economic impact, the possibilities of reducing them with vaccination programmes and the difficulties in carrying them out. The role of nursing, pharmacy services, patient associations and the health administration itself in changing the current situation was discussed. Prospects for new vaccines were discussed and we speculated on the future in this field. Finally, particularly relevant ethical aspects in decision-making regarding vaccination were discussed, which must be faced by both individuals and states. We have tried to summarize, at the end of the presentation of each question, the environment of opinion that was agreed with all the members of the table.

Background:The cytokine storm syndrome (CSS) associated with COVID-19 pneumonia occurs in up to 20% of the admitted patients causing high morbidity and mortality [1]. In the COVID High-intensity Immunosuppression in Cytokine storm syndrome (CHIC) study [1] we reported that CSS patients, who despite high-dose methylprednisolone (MP) treatment still showed severe respiratory deterioration, received subsequent single dose tocilizumab (TCZ) treatment. Our clinical experience with TCZ, every 4 weeks in RA, where a pre-dose serum concentration of > 1 µg/ml is sufficient to block all interleukin (IL)-6 receptors and thereby induce and maintain clinical remission, prompted further investigation of TCZ pharmacokinetics in patients with COVID-19 CSS [1,2].Objectives:In this pharmacokinetic study we investigated the clinical-pharmacokinetic rationale for a single TCZ dose in a subset of COVID19 induced CSS patients.Methods:Patients with COVID-19-associated CSS, defined as rapid respiratory deterioration plus at least two biomarker elevations (C-reactive protein (CRP) >100 mg/L; ferritin >900 μg/L; D-dimers >1500 μg/L), received per protocol high-dose intravenous MP for 5 consecutive days. If the respiratory condition had not improved sufficiently, TCZ (8 mg/kg, max. 800 mg) single infusion was added on or after day 2[1]. TCZ serum samples were drawn at TCZ day 1, 3 and 10 to assess TCZ serum concentrations with a validated ELISA-method. A nonlinear-mixed effects model was developed based on all concentration time data to characterise TCZ pharmacokinetics (NONMEM). Subsequently individual pharmacokinetic parameters (AUC0-inf, Cmax, time above 1 µg/ml) were estimated and TCZ concentration-time observations were plotted against the individual predicted concentrations to visualize the complete TCZ concentration-time curve.Results:In total, 34 patients with COVID19 induced CSS still showing clinical deterioration upon MP treatment received TCZ per protocol [mean (SD) age: 62 (12) years, 22% female, baseline mean (SD) bodyweight: 87 (17) kg, CRP: 108 (833) mmol/L, ferritin: 1653 (911) µg/L, D-dimers 4462 (7272) µg/L]. TCZ clearance was described by a homogeneous population-kinetics model yielding 87 serum samples. TCZ serum concentrations followed a biphasic course [Distribution volume 5.0 L (3.3-7.3), Area Under the Curve0-∞1st dose (682 (397-913) mg/L*days), Cmax 137 mg/L (88 – 199), half-life (linear) 3.5 days (2.3-4.1)]. In all patients, TCZ serum concentrations remained above the theoretical maximum IL-6 receptor occupancy concentration of 1 µg/ml for at least 12 days, depicted in Figure 1.Figure 1.Predicted concentration-time profiles after single dose tocilizumab in 34 methylpred-nisolone pretreated patients with COVID-19 induced cytokine storm syndrome. Dashed line: maximum IL-6 receptor occupancy concentration 1 µg/mlConclusion:Based on our study results on the pharmacokinetics of TCZ in patients with severe COVID-19 induced CSS we conclude that the clearance of TCZ is faster compared to RA-patients at steady state. However, our observations indicate that a single dose of tocilizumab in CSS-patients is enough to cover IL-6 mediated hyperinflammation. Restricting TCZ to a single dosage can prevent overtreatment, drug shortage and saves costs, while still maintaining efficacy, as most patients will have overcome their hyperinflammatory period of the CSS after 10-14 days.References:[1]Ramiro S. Mostard R.L.M. et al. Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study. Ann Rheum Dis 2020;79(9):1143-1151.[2]Nishimoto N, Terao K et al. Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood. 2008;112:3959-3964.Acknowledgements:The authors are grateful to all patients, nurses and physicians who participated in this study.Disclosure of Interests:None declared

Human population growth and the activities resulting in habitat destruction are a threat to biodiversity worldwide. Despite the recognized importance of dung beetles in supporting tropical forest ecosystems, our understanding of their susceptibility to anthropogenic pressures remains limited. Previous research detailed the overall consequences of habitat loss driven by human activities to tropical dung beetle assemblages and traits. The work pointed out main knowledge gaps and outlined future work inspiring a surge in research. After a decade, we build upon the previous review, and bring an update to this topic with the aim of disentangling the confounding drivers impacting dung beetle responses. Using a comprehensive meta-analytical approach, we address the main geographical constraints and limitations, summarize the most up-to-date information, and draw new conclusions on the consequences of human activities to dung beetles. Our results help to draw together the patterns defining how human activities alter dung beetle abundance, species richness, community diversity and evenness. We show that beetle assemblage composition depends upon the origin and intensity of forest conversion, and has consequences for dung beetle associated ecosystem functions. Finally, we demonstrate that the depletion of large vertebrates throughout the tropics has indirect effects on beetle communities. As a consequence, anthropogenic actions are likely to harm dung beetle populations both directly, through habitat loss, and indirectly, through the cascading effects of the loss of large mammals.

Supplemental Material for Are serum autoantibodies associated with brain changes in systemic lupus erythematosus? MRI data from the Leiden NP-SLE cohort by C. Magro-Checa, S. Kumar, S. Ramiro, L.J. Beaart-van de Voorde, J. Eikenboom, I. Ronen, J de Bresser, M.A van Buchem, T.W. Huizinga and G.M. Steup-Beekman in Lupus

Schizophrenia is a serious mental disorder affecting approximately 29 million people worldwide. The ideal treatment and care of patients with schizophrenia should be provided by a multidisciplinary 'team' involving psychiatrists, nurses and other healthcare professionals, together with carers and patients. In light of the key role carers play in the care of patients with schizophrenia, the present survey was designed to assess the opinions of family members and friends of patients with schizophrenia across Europe and to ascertain their attitudes towards the illness, medication and adherence to medication. Among carers participating in this survey, there was widespread awareness of the issues involved in supporting patients with schizophrenia and the importance of their role in improving poor adherence to medication. Three differences in opinion emerged between the views of carers and psychiatrists; psychiatrists rely more on the patient themselves when assessing adherence than carers would recommend; in contrast to psychiatrists, many carers believe the illness itself contributes to non-adherence; two thirds of carers think that schizophrenia medication damages health (higher than estimated by psychiatrists). The findings from the present survey, taken together with the results from the Adherencia Terapéutica en la Esquizofrenia surveys of psychiatrists and nurses, support the need for a collaborative approach to the issue of treatment nonadherence. In particular, healthcare professionals should recognize the valuable contribution that family carers can make to improve treatment adherence and consequently clinical outcomes for patients with schizophrenia. Schizophrenia carries a significant burden for families providing care. The Adherencia Terapéutica en la Esquizofrenia (ADHES) carers' survey was designed to assess the opinions of family and friends of patients with schizophrenia across Europe and ascertain their attitudes towards the illness, medication and adherence to medication. A questionnaire-based cross-sectional survey of 138 carers across 16 European countries. Interpretation of results was based on a descriptive comparison of responses. Carers recognized the importance of medication to help patients get better (76%) and improve their quality of life (76%) and relationships (74%). Sixty-seven per cent believed medication damages general health. Sixty-five per cent reported that treatment adherence was a burden for patients. Thirty-eight per cent indicated that it was a daily struggle to get patients to take their medication. Fifty per cent perceived that medication administered every few weeks rather than daily was quite/very important. Ninety-three per cent agreed on the importance of family support to boost adherence, with education and information deemed important for families and patients. Carers rely less on the patient themselves when assessing adherence than psychiatrists. The burden faced by carers and patients in taking medication provides an opportunity for healthcare professionals to provide support in a multidisciplinary 'team' involving psychiatrists, nurses and carers.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a distinctive lymphocyte rich vasoformative proliferation comprising epithelioid-appearing endothelial cells with partially canalized capillary vessels in a lymphohistiocytic and eosinophil rich environment. ALHE presents clinically as single or multiple pink-brown dome-shaped papules or nodules, most commonly on the ear and peri-auricular area, followed by the face, and scalp. ALHE involving the subungual unit is rare with only 5 previously reported cases and all involved the underlying bone. The authors describe a case of a painful subungual nodule of the left 1st fingernail in a 48-year-old woman. An excisional biopsy was performed confirming a diagnosis of ALHE. There was no bone involvement and immediately following excision of the tumor, there was complete resolution of her symptoms. Our patient's presentation expands upon the clinical and histopathological spectrum of subungual ALHE.

Background and aims. Osteoarthritis (OA) is a degenerative joint pathology associated with pain, reduced range of motion, impaired function and reduction in quality of life with a high prevalence among the elderly population. Although its complete etiology is not known, it is characterized by a progressive loss of articular hyaline cartilage in the joints with the involvement of multiple inflammatory mediators. Hydrogen sulfide, traditionally classified as a soluble toxic gas, is now considered the third endogenous gasotransmitter and is emerging as a potential regulator of inflammation. Balneotherapy or bathing in thermal or mineral waters is used as a non-invasive treatment for several conditions and one of the main features of sulfurous water is the presence of hydrogen sulfide which might offer therapeutic value in the treatment of OA. The purpose of this review is to provide an overview of the potential therapeutic benefits of hydrogen sulfide as an anti-inflammatory approach to osteoarthritis.

High blood pressure (HBP) is a modifiable cardiovascular risk factor and its detection at early ages may allow strategies to be designed to reduce cardiovascular risk in adulthood.To provide blood pressure (BP) values in a sample of adolescents using an electronic oscillometric device.BP was measured according the European Society of Hypertension guidelines using an oscillometric device. Height and weight were also measured. Four height groups were used in order to associate the 90, 95, and 99 percentiles with systolic BP (pSBP) and diastolic BP percentiles (pDBP) for sex and age: H150 (≤ 150cm), H160(151-160cm), H170(161-170cm), and H180(≥171cm).Data from 2,758 students aged 12-17 years were included in the analysis. BP increases with age, with differences of up to 11mmHg in boys vs. 3mmHg in girls for SBP and 3mmHg vs. 1mmHg for DBP. In high SBP, for the younger adolescents, the difference related to height was 15mmHg in boys vs. 8mmHg in girls, with no significant increase in the older ones in either gender. The high BDP varied depending on the height, 10mmHg in younger boys and 3mmHg in older ones, while in girls the variation was 3mmHg for all ages.SBP/DBP in adolescents increases with age and also with height, giving similar figures in the taller ones, regardless of age.

Association between elevated C-reactive protein (CRP) serum levels and subclinical atherosclerosis and cardiovascular (CV) events was described in rheumatoid arthritis (RA). CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 exert an influence on elevated CRP serum levels in non-rheumatic Caucasians. Consequently, we evaluated the potential role of these genes in the development of CV events and subclinical atherosclerosis in RA patients. Three tag CRP polymorphisms and HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were genotyped in 2,313 Spanish patients by TaqMan. Subclinical atherosclerosis was determined in 1,298 of them by carotid ultrasonography (by assessment of carotid intima-media thickness-cIMT-and presence/absence of carotid plaques). CRP serum levels at diagnosis and at the time of carotid ultrasonography were measured in 1,662 and 1,193 patients, respectively, by immunoturbidimetry. Interestingly, a relationship between CRP and CRP serum levels at diagnosis and at the time of the carotid ultrasonography was disclosed. However, no statistically significant differences were found when CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were evaluated according to the presence/absence of CV events, carotid plaques and cIMT after adjustment. Our results do not confirm an association between these genes and CV disease in RA, The present work was financed by European Union FEDER funds and “Fondo de Investigación Sanitaria” (grants PI12/00060 and PI15/00525) and RETICS Programs RD12/0009 from “Instituto Carlos III de Salud” (Health Ministry, Spain) and in part by grants from the European IMI BTCure Program. RL-M and BU are financed by RETICS (RD12/0009/0013). FG is supported by a Sara Borrell postdoctoral fellowship (CD15/00095).

This study aims to characterise the rainfall exceptionality and the meteorological context of the 20 February 2010 flash-floods in Madeira (Portugal). Daily and hourly precipitation records from the available rain-gauge station networks are evaluated in order to reconstitute the temporal evolution of the rainstorm, as its geographic incidence, contributing to understand the flash-flood dynamics and the type and spatial distribution of the associated impacts. The exceptionality of the rainstorm is further confirmed by the return period associated with the daily precipitation registered at the two long-term record stations, with 146.9 mm observed in the city of Funchal and 333.8 mm on the mountain top, corresponding to an estimated return period of approximately 290 yr and 90 yr, respectively. Furthermore, the synoptic associated situation responsible for the flash-floods is analysed using different sources of information, e.g., weather charts, reanalysis data, Meteosat images and radiosounding data, with the focus on two main issues: (1) the dynamical conditions that promoted such anomalous humidity availability over the Madeira region on 20 February 2010 and (2) the uplift mechanism that induced deep convection activity.

Introduction/Background Survivors of a traumatic brain injury (TBI) frequently suffer from urinary dysfunction. Possible causes are midbrain dysfunction and primary lesions, but cognitive and behavior factors may also play a role. Overactive bladder (OAB) is a frequent urinary disturbance as opposed to urinary retention. In this study, we aim to investigate altered findings in urodynamic tests and possible relations to other TBI outcomes. Material and method A retrospective study was conducted with 24 post-TBI patients (21 male, 3 female) admitted to our unit during a 3 year period. Exclusion criteria included stroke, spinal cord injury, previous history of urological pathology or surgery and absence of urodynamic evaluation. Information was gathered relative to results of urodynamics, TBI imaging, initial GCS scale, urinary symptoms, vesical regime, neuropsychological and ultrasound results. Results Of the 24 patients studied, all had severe TBI with a mean age of 40.1 years and a predominance of motor vehicle related accidents (66.7%) and axonal diffuse injury (62.5%). Median time from TBI was 7.5 months and only 2 patients had a normal urodynamic study. Urinary symptoms were present in 17 (70.8%) patients and the majority (58.3%) had filling symptoms. There was previous history of urinary tract infection in 32% patients. Neuropsychological evaluation was altered in all but one of the assessed patients. The majority had OAB (62.4%) and altered bladder sensation (70.8%). Mean total vesical capacity was 343.6 mL. Elevated postvoid residual volume (37.5%) and detrusor sphincter dyssynergia (37.5%) was observed. Conclusion Most patients had urinary symptoms and an overactive bladder. A subset of patients showed detrusor sphincter dyssynergia, a finding not frequently described. Cognitive impairment can play a role in urologic dysfunction and pseudodyssynergia might be present during the urodynamic test. Further studies are needed to assess urologic dysfunction in severe TBI survivors.

CARE Checklist (2013) of information to include when writing a case report. (DOCX 1483 kb)

Montes, Ariana et al., [Introduction] We have hypothesized that incompatibility between the G1m genotype of the patient and the G1m1 and G1m17 allotypes carried by infliximab (INX) and adalimumab (ADM) could decrease the efficacy of these anti-tumor necrosis factor (anti-TNF) antibodies in the treatment of rheumatoid arthritis (RA)., [Methods] The G1m genotypes were analyzed in three collections of patients with RA totaling 1037 subjects. The first, used for discovery, comprised 215 Spanish patients. The second and third were successively used for replication. They included 429 British and Greek patients and 393 Spanish and British patients, respectively. Two outcomes were considered: change in the Disease Activity Score in 28 joint (ΔDAS28) and the European League Against Rheumatism (EULAR) response criteria., [Results] An association between less response to INX and incompatibility of the G1m1,17 allotype was found in the discovery collection at 6 months of treatment (P = 0.03). This association was confirmed in the replications (P = 0.02 and 0.08, respectively) leading to a global association (P = 0.001) that involved a mean difference in ΔDAS28 of 0.4 units between compatible and incompatible patients (2.3 ± 1.5 in compatible patients vs. 1.9 ± 1.5 in incompatible patients) and an increase in responders and decrease in non-responders according to the EULAR criteria (P = 0.03). A similar association was suggested for patients treated with ADM in the discovery collection, but it was not supported by replication., [Conclusions] Our results suggest that G1m1,17 allotypes are associated with response to INX and could aid improved therapeutic targeting in RA., Funding was provided by grants PI11/01048, PI12/01909 and by RETICS Program, RD08/0075/0019 and RD12/0009/0008 (RIER) of the Instituto de Salud Carlos III (Spain) that are partially financed by the European Regional Development Fund of the European Union.

The IL-6 -174G/C genetic variant has recently been associated with the clinical response to etanercept therapy in rheumatoid arthritis (RA) patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the antitumor necrosis factor (anti-TNF) treatment outcome in RA.Our study population was composed of 199 Spanish patients with RA receiving anti-TNF therapy. The IL-6 -174G/C (rs1800795) genetic variant was genotyped using the TaqMan allelic discrimination technology. Patients were classified, according to the European League Against Rheumatism (EULAR) criteria, as responders (good and moderate response) and nonresponders at 6, 12, 18, and 24 months after the first infusion.The -174*G allele was significantly associated with a good or moderate EULAR response at 12 [P=0.015, odds ratio (OR)=2.93, 95% confidence interval (CI) 1.29-6.70], 18 (P=4.54E-03, OR=5.17, 95% CI 1.80-14.85), and 24 months (P=4.54E-03, OR=14.86, 95% CI 2.91-75.91). A meta-analysis combining these data with the results from a previous study confirmed this association (P=1.89E-02, OR=1.80, 95% CI 1.13-2.87, at 12 months).Our results support the role of the -174G/C IL-6 polymorphism as a genetic marker of responsiveness to anti-TNF therapy.

[Introduction] In this study, our aim was to elucidate the role of four polymorphisms identified in a prior large genome-wide association study (GWAS) in which the investigators analyzed the responses of patients with rheumatoid arthritis (RA) to treatment with tumor necrosis factor inhibitors (TNFi). The authors of that study reported that the four genetic variants were significantly associated. However, none of the associations reached GWAS significance, and two subsequent studies failed to replicate these associations., [Methods] The four polymorphisms (rs12081765, rs1532269, rs17301249 and rs7305646) were genotyped in a total of 634 TNFi-treated RA patients of Spanish Caucasian origin. Four outcomes were evaluated: changes in the Disease Activity Score in 28 joints (DAS28) after 6 and 12 months of treatment and classification according to the European League Against Rheumatism (EULAR) response criteria at the same time points. Association with DAS28 changes was assessed by linear regression using an additive genetic model. Contingency tables of genotype and allele frequencies between EULAR responder and nonresponder patients were compared. In addition, we combined our data with those of previously reported studies in a meta-analysis including 2,998 RA patients., [Results] None of the four genetic variants showed an association with response to TNFi in any of the four outcomes analyzed in our Spanish patients. In addition, only rs1532269 yielded a suggestive association (P = 0.0033) with the response to TNFi when available data from previous studies were combined in the meta-analysis., [Conclusion] Our data suggest that the rs12081765, rs1532269, rs17301249 and rs7305646 genetic variants do not have a role as genetic predictors of TNFi treatment outcomes., The work done at Consejo Superior de Investigaciones Científicas (CSIC) was supported by AbbVie Pharmaceuticals and partially by Cooperative Research Thematic Network (RETICS) programs RD08/0075/0011, RD12/0009/0004, RD12/0009/0012 and RD12/0009/0016 (RIER); “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Madrid, Spain); and grants from the European Innovative Medicines Initiative (IMI) Be the Cure for Arthritis (BTCure) program. The work done in Santiago de Compostela was funded by Fondo de Investigación Sanitaria from ISCIII, (Health Ministry, Madrid, Spain), grants PI11/01048, PI12/01909, RD08/0075/0019 and RD12/0009/0008, which are partially financed by the European Regional Development Fund of the European Union. The sponsors had no role in the design of the study; in the collection, analysis or interpretation of data; or in the preparation, review or approval of the manuscript.

This study comprised a sample of 31 patients with Class III malocclusion (21 girls and 10 boys), with ages ranging from 5 years 2 months to 11 years 6 months. All patients were in the deciduous or mixed dentition. The indicated treatment was rapid maxillary expansion, immediately followed by maxillary protraction with the facial mask. Mean treatment time was 8 months, varying from 4 to 24 months. The therapy induced both dental and skeletal alterations. Skeletal alterations consisted of maxillary anterior displacement and mandibular downward and backward rotation, improving facial profile. Dental alterations, known as dentoalveolar compensations, consisted of a tendency of labial tipping of the maxillary incisors and lingual tipping of the mandibular incisors.

We aimed to assess the long-term safety and tolerability of imatinib in diffuse cutaneous systemic sclerosis (dcSSc).In this open-label, single-arm, extension-phase clinical trial, patients continued imatinib for 24 months following 12 months of initial treatment.Seventeen patients were enrolled. Forty of 92 adverse events (AE) and 0/6 serious (S) AEs were possibly related to medication. The MRSS decreased from a median of 21 to 16, (p=0.002).This study demonstrates long-term safety and tolerability of imatinib in a substantial proportion of patients with dcSSc. This is important in evaluating the relevance of this therapy in a chronic disease such as SSc.

To evaluate the impact of the application of the EULAR task force recommendations in the cardiovascular (CV) risk assessment of rheumatoid arthritis (RA) patients according to a national calibrated SCORE.Two hundred and one consecutive RA patients seen at the rheumatology outpatient clinics of the University Hospital 'San Cecilio', Granada, Southern Spain, were studied. Information on demographic, classic CV risk factors, history of CV events and disease clinical features were obtained. Both the systematic coronary risk evaluation (SCORE) risk index and the modified SCORE (mSCORE) following the EULAR recommendations were performed.Based on the classic CV risk factors the mean ± standard deviation SCORE was 2.2 ± 2.6 (median 2). Twenty-two (11%) patients were above the threshold of high risk for the Spanish population. Following the EULAR recommendations 52 of the 124 patients (41.93%) initially classified as having intermediate risk were reclassified as having high CV risk. Therefore, the mean mSCORE was 3.3 ± 4 (median 3) and, due to this, 74 (36.8%) patients were above the threshold of high CV risk for the Spanish population. As expected, patients who had experienced CV events were older, had more CV risk factors and higher mSCORE than those without CV events.These observations support the claim that the mSCORE should be specifically adapted to the population to be assessed. However, the use of additional tools should be considered in an attempt to fully identify high-risk RA patients.

Objective: To analyse the role of the PTPN22 and CSK genes, previously associated with autoimmunity, in the predisposition and clinical phenotypes of giant cell arteritis (GCA). Methods: Our study population was composed of 911 patients diagnosed with biopsy-proven GCA and 8136 unaffected controls from a Spanish discovery cohort and three additional independent replication cohorts from Germany, Norway and the UK. Two functional PTPN22 polymorphisms (rs2476601/R620W and rs33996649/R263Q) and two variants of the CSK gene (rs1378942 and rs34933034) were genotyped using predesigned TaqMan assays. Results: The analysis of the discovery cohort provided evidence of association of PTPN22 rs2476601/R620W with GCA (PFDR=1.06E-04, OR=1.62, CI 95% 1.29 to 2.04). The association did not appear to follow a specific GCA subphenotype. No statistically significant differences between allele frequencies for the other PTPN22 and CSK genetic variants were evident either in the case/control or in stratified case analysis. To confirm the detected PTPN22 association, three replication cohorts were genotyped, and a consistent association between the PTPN22 rs2476601/R620W variant and GCA was evident in the overall meta-analysis (PMH=2.00E-06, OR=1.51, CI 95% 1.28 to 1.79). Conclusions: Our results suggest that the PTPN22 polymorphism rs2476601/R620W plays an important role in the genetic risk to GCA.

Objective Signal-transducer and activator of transcription protein 3 ( STAT3 ) gene encodes a transducer and transcription factor that plays an important role in many cellular processes such as cell growth, apoptosis and immune response. Several STAT3 genetic variants have been associated to different autoimmune diseases. Our aim was to reveal the possible STAT3 influence in other immune-mediated diseases such as psoriatic arthritis (PsA) and Behcet disease (BD). Methods The STAT3 rs744166 and rs2293152 polymorphisms were genotyped using predesigned TaqMan® assays in a total of 335 PsA patients, 217 BD patients, and 1844 ethnically matched healthy controls of Spanish Caucasian origin. Results A statistically significant association of the STAT3 rs744166 ∗ G allele with PsA was observed ( P -value = 1.36 × 10 −3 , OR 1.35). The detected effect was more evident when the rs744166 ∗ GG homozygote frequencies were compared between PsA patients and controls (genotype P -value = 9.77 × 10 −5 , OR 1.82). In contrast, the allele and genotypic distributions of rs744166 polymorphism showed no significant differences between patients with BD and control subjects (allelic P -value = 0.80, OR 1.03). Additionally, no evidence of association was detected between the rs2293152 genetic variant and both studied diseases. Conclusion Our results suggest for the first time that the STAT3 gene might be involved in PsA but not in Behcet’s disease predisposition.

The emission properties of a new phosphor based on LiTaO3:Tb3+ are described. It is shown to be a storage phosphor, i.e., after previous x‐ray exposure, Tb3+ emission in green‐red region of spectrum can be photostimulated by light in 400–800 nm spectral range. Emission centers (Tb3+ ions), electron storage centers (oxygen vacancies) and competing nonradiative recombination centers (oxygen ion and Li vacancy couples), are recognized as the key elements in the energy transfer processes and overall emission efficiency of LiTaO3:Tb3+.

LiTaO3: Tb3+ phosphors, prepared as crystalline powders, exhibit, at room temperature, strong green luminescence both during X-ray exposure (Direct Luminescence, DL) and subsequently, when stimulated in the 400-800 nm range (Photo-Stimulated Luminescence, PSL). Due to the high efficiency of the PSL, similar to that of the well-known UV-blue emitting BaFClxBr1−x:Eu2+ phosphors, the new storage phosphors based on LiTaO3:Tb3+ can find applications as X-ray sensors in Medical Digital Radiography and other radiation sensing fields. Both the direct and photo-stimulated luminescence efficiencies depend on the Li/Ta ratio, on the Tb3+ ions concentration and on the presence of co-dopants like, as in this case, Mg2+ alkali earth ions. Mg2+ ions improve the D.L. and have also a positive effect on the P.S.L. up to a nominal concentration of 0.015-0.02 at/mol. The results of the luminescence properties are here interpreted, with the support of diffuse reflectance data and lattice parameter measurements, on th...

Background Rheumatoid arthritis (RA) is an autoimmune pathology associated with increased risk of cardiovascular (CV) disease and subclinical atherosclerosis 1 . Consequently, both inflammatory diseases share common molecules involved in its pathogenesis. In this sense, interleukin 17A (IL-17A) is a pro-inflammatory cytokine involved in the regulation of immune responses and chronic inflammation 2 . Objectives To evaluate the potential association between different IL-17A polymorphisms and CV events, as well as subclinical atherosclerosis, in a large cohort of Spanish RA patients. Methods Five IL-17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were genotyped by TaqMan assays in a 7900 HT Real-Time polymerase chain reaction system in 1,974 Spanish patients diagnosed with RA (fulfilling the 2010 American College of Rheumatology classification criteria for RA 3 ), recruited from different Spanish hospitals. 318 patients (16.1%) had experienced CV events, and 822 had undergone carotid ultrasonography studies to assess subclinical atherosclerosis (presence/absence of plaques and carotid intima media thickness [cIMT]). The relationship between IL-17A alleles, genotypes and haplotypes and CV events, presence/absence of plaques and cIMT values was assessed. Results were adjusted for sex, age at diagnosis and traditional CV risk factors. Results No statistically significant differences were observed when allelic/genotypic frequencies of each IL-17A polymorphism were assessed regarding presence/absence of CV events, plaques or cIMT values. This was also the case when the five polymorphisms were combined to form haplotypes. Conclusions Our results do not confirm an association between the five IL-17A polymorphisms studied and the development of CV events or subclinical atherosclerosis in our cohort of Spanish RA patients. References Avina-Zubieta JA et al. Ann Rheum Dis. 2012;71:1524–9. Shabgah AG et al. Postepy Dermatol Alergol. 2014;31(4):256–61. D. Aletaha T et al. Arthritis Rheum. 2010;62:2569–81. Acknowledgement This study was supported by European Union FEDER funds and “Fondo de Investigaciόn Sanitaria” (PI12/00060 and PI15/00525) (Spain), and partially supported by RETICS Programs RD12/0009 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain). FG is a recipient of a Sara Borrell postdoctoral fellowship from the ISCIII (Spain) (CD15/00095). RL-M and BU are supported by funds from the RETICS Program (RIER) (RD12/0009/0013). Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) is an autoimmune inflammatory disease associated with accelerated atherosclerosis and increased cardiovascular (CV) disease. Elevated levels of the C-reactive protein (CRP) are related to an increase risk of coronary artery disease [1] and stroke [2]. Recently, PCR, GCKR, HNF1A, LEPR, ASCL1 and NLRP3 have been associated with CRP levels in non-rheumatic population [2]. Objectives We aimed to determine the potential role of these genes in the development of CV disease and subclinical atherosclerosis in patients with RA. Methods Genotyping was performed in 2,384 Spanish RA patients by TaqMan assays. Subclinical atherosclerosis was determined by carotid ultrasonography (US) in 1,193 patients. Results No statistically significant differences were found when PCR, GCKR, HNF1A, LEPR, ASCL1 and NLRP3 were assessed according to the presence/absence of CV disease. It was also the case when patients were stratified according the presence/absence of subclinical atherosclerosis. Conclusions Our results do not confirm an association between these genes and the development of CV disease and subclinical atherosclerosis in patients with RA. References Danesh et al. N Engl J Med 2004, 350(14):1387–1397; Ridker et al. N Engl J Med 1997, 336(14):973–979; Dehghan A et al. Circulation, 123(7):731–738. Acknowledgement This study was supported by European Union FEDER funds and “Fondo de Investigaciόn Sanitaria” (grants PI12/00060 and PI15/00525) from `Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain). It was also partially supported by RETICS Programs RD12/0009 (RIER) from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain), and in part by grants from the European IMI BTCure Program. RL-M and BU is supported by funds from the RETICS Program (RIER) (RD12/0009/0013). FG is a recipient of a Sara Borrell postdoctoral fellowship from the “Instituto Carlos III de Salud” at the Spanish Ministry of Health (Spain) (CD15/00095). Disclosure of Interest None declared

The radiofrequency plasma technique involving mixtures of CF4+O2 gases has been applied to the surface treatment of high Tc superconducting oxides (YBa2Cu3O7−δ). Investigation of the various experimental parameters of the process has shown that the improvement of the critical current density, Jc, mainly depends on the inlet precursor composition CF4+τ%O2, on the total pressure and on the reaction time. The presence of fluorine in the bulk of the ceramics has been observed from electron microprobe analysis, together with an increase of the “Cu3+” content. The plasma-enhanced fluorination (PEF) treatment improves the superconducting properties of the materials: both values of the resistivity in the normal state and of the superconducting transition width are reduced and the critical transition temperature is improved by about 1 K.

Mechanisms of interaction between the reactive species of a (CF 4 +O 2 ) plasma and YBa 2 Cu 3 O 7-δ ceramics have been proposed through detailed angle-resolved X-ray photoelectron spectroscopic analyses. At the surface of the outer grains, the plasma treatment removes (OH) - and (CO 3 ) 2- species contained in the degradation layer and gives rise to a fluoride-rich layer, whereas in the bulk of the material the occurrence of metal-fluorine bonds in the superconducting phase has been assumed. An increase of the oxidation state of copper has been also detected, confirming the oxidizing effect of the plasma treatment. A comparison with the oxidation mechanisms obtained by fluorine gas treatment is proposed

The present work is devoted to the study of the relationship between microstructure and electrical transport properties in melt-textured YBa 2 Cu 3 O 7−δ ceramics. The production process described gives rise to a preferential orientation within large domains. SEM micrographs show long platelets stacked in a parallel arrangement. A.c. susceptibility measurements reveal a very low level of weak links. Direct and indirect critical current measurements, performed on long and small samples, respectively, reveal large differences. This discrepancy is ascribed to pseudo random orientation of the large domains, as confirmed by rocking curve characterizations. Pole figure measurements show that the preferential orientation of the free surfaces of the bulk sample appears to be 〈113〉 or 〈103〉 whichever face of the parallelepiped is considered. The latter observation is in agreement with the existence of non-coherent regions inside the sample. Consequently, a high critical current density (12 000 A cm −2 ) can only be obtained for samples where long range texturing of the order of centimetres has been achieved.

L'étude de la cinétique d'oxydation des céramiques d'YBa2Cu3O7-δ frittées à basse température montre que les faibles Jc obtenus sont pour une part au moins liés à la difficulté de réoxyder complètement ces matériaux du fait de la présence d'une fine couche amorphe aux interfaces solide/gaz. L'étude de la diffusion de l'oxygène au sein de matériaux préalablement carbonatés montre que les carbonates résiduels sont à l'origine de la formation de ces barrières de diffusion.

Silicon nitride films were deposited by pyrolytic chemical vapour deposition (CVD) and plasma-enchanced CVD techniques. The effects on the stoichiometry of variations in the reactant gas flow were evaluated. Electron spectroscopy for chemical analysis, Fourier transform infrared (FTIR) and secondary ion mass spectrometry (SIMS) were used in order to clarify the differences in the composition of the films. The analytical information obtained with these techniques included the silicon-to-nitrogen ratio, N—H and Si—H group content, surface oxide and bulk contamination. It was found that the classic FTIR approach was unable to detect the low Si—H content in CVD films. This low Si—H level could, however, be detected by SIMS without interference at 31 a.m.u. as a 30SiH + species.

In this paper, the Atlas of Global Solar Radiation of the Madeira Archipelago (Portugal) is presented. In a first approach, horizontal global solar irradiances at ground level are obtained applying the Heliosat-2 method to earth images taken by the Meteosat-6 satellite. These values are then integrated and averaged to obtain the “first approach” monthly average daily global solar radiation values in each pixel of the image. These results are, in turn, calibrated (normalized) with data of solar radiation measured in six meteorological stations in the region. Both data base are from the period January 2002–December 2005.

This paper focuses on the optimization of hybrid off-grid PV-Wind systems in six climatic areas of the Madeira archipelago (Portugal), both from the technical and economical points of view. The areas are characterized by the variables recorded in six corresponding meteorological stations during the period 2002–2005. To facilitate the comparison of the systems, energy productions are given as specific values related to the square meter of horizontal land occupied by the systems. The DC PV electric generation per square meter of module (and horizontal land) in the sites of the stations was obtained in a parent paper. The wind electric generation is obtained from the wind daily data of the stations and considering an instantaneous Weibull distribution.

The aim of the paper is to characterize the daily evolution of horizontal global solar radiation and temperature in six climatic areas of the Madeira archipelago, from the daily data recorded in six corresponding meteorological stations. An average characteristic day is obtained for each month of the year in the four-year data period 2002–2005. In relation to solar radiation, a characteristic day is defined as the day of the month with the Sun trajectory closest to the daily average Sun trajectory of the month and the daily global horizontal solar irradiation equal to the daily average of the month. It is assumed a sine-type evolution of the global irradiances along the day. In relation to temperature, a characteristic day is also assumed to have a sine-type evolution along the daylight hours of the day, with the minimum and maximum values at sunrise and two hours after noon, respectively. The characteristic minimum and maximum values are obtained averaging the daily minimum and maximum values of the month, respectively.