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Objectives: To investigate the influence of genetic factors on persistence to treatment of early rheumatoid arthritis (RA) with methotrexate (MTX) monotherapy. Methods: We conducted a genome-wide association study (GWAS) in a sample of 3902 Swedish early RA patients initiating MTX in DMARD-monotherapy as their first ever DMARD. The outcome, short- and long-term persistence to this treatment, was defined as remaining on MTX at one and at three years, respectively, with no additional DMARDs added. As genetic predictors, we investigated individual SNPs, and a polygenic risk score (PRS) based on SNPs associated with RA risk. The SNP-based heritability of persistence was estimated overall and by RA serostatus. Results: No individual SNP reached genome-wide significance (p < 5e-8), neither for persistence at one nor at three years. The RA PRS was not significantly associated with persistence at one (RR = 0.98 (0.96-1.01)) nor three years (RR = 0.96 (0.93-1.00)). The heritability for persistence was estimated to be 0.45 (0.15-0.75) at one year and 0.14 (0-0.40) at three years. Results in seropositive RA were comparable to those in the analysis of RA overall, while heritability estimates and PRS RRs were attenuated towards the null in seronegative RA. Conclusions: Despite being the largest GWAS on an MTX treatment outcome to date, no genome-wide significant associations were detected. The modest heritability observed, coupled with the broad spread of suggestively associated loci, indicate that genetic influence is of polygenic nature. Nevertheless, persistence to MTX monotherapy was lower in patients with a greater genetic disposition, per the PRS, towards RA., Errata: Correction to: Genome-wide investigation of persistence with methotrexate treatment in early rheumatoid arthritis. Rheumatology, 2023; kead540. DOI: 10.1093/rheumatology/kead540

Objectives We aimed to investigate the risk of first primary cancer in patients with RA treated with janus kinase inhibitors (JAKi) compared with those who received biologic DMARDs (bDMARDs) in a real-world setting. Methods We performed an observational cohort study using the nationwide registers in Denmark. Patients with RA aged 18+ years, without a previous cancer diagnosis, and who initiated treatment with JAKi or bDMARDs from 1 January 2017 to 31 December 2020 were followed for any cancer (except non-melanoma skin cancer). We applied inverse probability of treatment weighting (IPTW) to account for covariate differences between treatment groups. IPTW-generated weights were used with cause-specific Cox (CSC) models to calculate hazard ratios (HRs) for cancer incidence in JAKi-treated compared with bDMARD-treated patients with RA. Results We identified 875 and 4247 RA patients treated with JAKi and bDMARDs, respectively. The JAKi group contributed 1315 person years (PYRS) and 19 cancers, the bDMARD group contributed 8597 PYRS and 111 cancers, with corresponding crude incidence rates per 1000 PYRS of 14.4 and 12.9. Comparing the two groups using weighted CSC models, a HR of 1.41 (95% CI 0.76, 2.37, 95% CIs) was seen for JAKi- vs bDMARD-treated patients with RA. Conclusion JAKi treatment in real-world patients with RA was not associated with a statistically significant increased risk of first primary cancer compared with those who received bDMARDs. However, several numerically increased risk estimates were detected, and a clinically important excess risk of cancer among JAKi recipients cannot be dismissed., OBJECTIVES: We aimed to investigate the risk of first primary cancer in patients with RA treated with janus kinase inhibitors (JAKi) compared with those who received biologic DMARDs (bDMARDs) in a real-world setting. METHODS: We performed an observational cohort study using the nationwide registers in Denmark. Patients with RA aged 18+ years, without a previous cancer diagnosis, and who initiated treatment with JAKi or bDMARDs from 1 January 2017 to 31 December 2020 were followed for any cancer (except non-melanoma skin cancer). We applied inverse probability of treatment weighting (IPTW) to account for covariate differences between treatment groups. IPTW-generated weights were used with cause-specific Cox (CSC) models to calculate hazard ratios (HRs) for cancer incidence in JAKi-treated compared with bDMARD-treated patients with RA. RESULTS: We identified 875 and 4247 RA patients treated with JAKi and bDMARDs, respectively. The JAKi group contributed 1315 person years (PYRS) and 19 cancers, the bDMARD group contributed 8597 PYRS and 111 cancers, with corresponding crude incidence rates per 1000 PYRS of 14.4 and 12.9. Comparing the two groups using weighted CSC models, a HR of 1.41 (95% CI 0.76, 2.37, 95% CIs) was seen for JAKi- vs bDMARD-treated patients with RA. CONCLUSION: JAKi treatment in real-world patients with RA was not associated with a statistically significant increased risk of first primary cancer compared with those who received bDMARDs. However, several numerically increased risk estimates were detected, and a clinically important excess risk of cancer among JAKi recipients cannot be dismissed.

Objectives To assess the association between venous thromboembolic (VTE) events and autoantibodies, following patients from RA diagnosis, measuring occurrence, levels and collective load of different autoantibodies against post-translational protein modifications, in particular recognizing citrullination (e.g. citrullinated fibrinogen) and RF by isotype. Methods A cohort of 2814 patients with newly diagnosed RA were followed for incident VTE through register linkages. Sera from RA diagnosis were centrally analysed for antibodies to second generation cyclic citrullinated peptides (anti-CCP2), 20 anti-citrullinated protein antibody (ACPA) fine-specificities, antibodies to additional protein modifications (carbamylation and acetylation) and RF by isotype. Association between baseline serology status and future VTE was analysed using Cox regression adjusted for age, sex and calendar period of RA diagnosis, overall and stratified by anti-CCP2 and RF positivity. Results During a median 16 years of follow-up, 213 first-ever VTE events were registered (5.0/1000 person-years). IgG anti-CCP2 (present in 65% of cohort) associated with VTE (hazard ratio [HR] = 1.33, 95% CI: 1.00, 1.78), in a dose-response manner. The risk of VTE increased with number of ACPA fine-specificities. IgM RF, but no other RF isotypes, associated with VTE (HR = 1.38, 95% CI: 1.04, 1.82). The associations were independent from smoking and HLA-DRB1 shared epitope alleles. None of the carbamylated or acetylated antibody reactivities associated with VTE. Conclusion Anti-CCP2, load of ACPA fine-specificities and IgM RF at RA diagnosis are associated with an increased risk of future VTE in RA. Antibodies to citrullinated fibrinogen did not differ substantially from other ACPA fine-specificities. Autoreactivity to other post-translational modifications was not associated with VTE risk.

Bakgrund: Ledgångsreumatism (RA) är en kronisk sjukdom som primärt påverkar lederna och har en inverkan på vuxnas dagliga liv. För att uppnå en mer omfattande insikt om sjukdomen och dess konsekvenser, är det av betydelse att utforska vuxnas upplevelser av att leva med RA. Denna insikt är nödvändig för att tillhandahålla adekvat vård och tillgodose de befintliga behoven. Syfte: Syftet med litteraturstudien är att undersöka vuxnas upplevelser av att leva med RA.Metod: En litteraturöversikt baserad på 12 kvalitativa artiklar har genomförts, där urvalet fokuserar på personer över 18 år med diagnosen RA. Genom en kvalitativ metodologi samlades data hämtade från databaserna Cinahl och Pubmed. Artiklarna kvalitet granskades enligt SBU:s bedömningsmall och resultatet analyserades enligt Popenoe m.fl. analysmetodik. Resultat: 3 huvudteman framkom, dessa teman var fysisk påverkan, social påverkan och självbild. Elva subkategorier identifierades, dessa var Upplevelsen av trötthet, Upplevelsen av smärta och kronisk stelhet, Upplevelsen av kvinnors sexuella hälsan, Strategier för att hantera vardagen, Upplevelsen av familje- och vänskapsrelationer, Upplevelsen av arbetsrelationer, Upplevelsen av sexuella relationer, Strategier kring arbetsrelaterad påverkan, Upplevelsen av förändrad kropp, Upplevlesen av att vara beroende av andra och Strategier kring självbilden. Konklusion: Resultatet belyste de utmaningarna som vuxna med RA stöter på dagligen. De dagliga utmaningarna sträcker sig över de fysiska- och psykiska aspekter samt förändringar i självbilden. Vidare framkom det i studien att RA har även en påverkan på kvinnors sexuella hälsa. För grundutbildade sjuksköterskor är det av betydelse att förstå vuxnas upplevelser och deras hantering av sjukdomen. Detta för att kunna tillgodose den vård och stöd som krävs för att förbättra deras övergripande livskvalitet.

Abstrakt Bakgrund: Reumatoid artrit (RA) är en progressiv, långvarig och systemisk autoimmun sjukdom som kännetecknas av fluktuerande symtom som smärta, trötthet och svullna leder. Sjukdomen kan lindras men inte botas. RA är ett folkhälsoproblem, där den vanligaste åldern för utbrott är vid 40 års ålder och uppåt. Sjukdomsaktiviteten har stor inverkan på de drabbade individerna och deras förmåga att utföra aktiviteter i det dagliga livet. Många känner sig begränsade av smärtan. Upplevelsen av smärta gör att många personerna blir socialt isolerade, då de inte längre kan ägna sig åt de aktiviteter som de upplever som meningsfulla. Många påverkas i sitt arbete, då sjukdomen orsakar både smärta samt minskad handstyrka. Syftet: I denna studie var syftet att genom en Scoping review kartlägga vad tidigare forskning säger om smärtans påverkan på dagliga aktiviteter hos personer med Reumatoid Artrit. Metod: Studien är utformad som en scoping review. Artiklarna var framtagna i databaserna Cinahl, Medline och PsycInfo. Totalt inkluderades 14 artiklar i studien. Resultat: Forskningsresultaten indikerar att personer med RA begränsas i sina dagliga aktiviteter på grund av smärtan. Trots detta väljer många personer att delta i olika aktiviteter som en distraktion från smärtan. De hittar andra alternativa sätt att utföra aktiviteterna på för att få aktiviteterna att fungera för dem. En stöttande omgivning och en tillåtande miljö visar sig ha en positiv inverkan på aktivitet engagemanget och kan minska begränsningarna. Slutsats: Att leva med RA kan vara en utmaning, smärta begränsar personer från att delta i aktiviteter de upplever som meningsfulla. Detta kan leda till social isolering och ibland tvingas personer med RA att gå i förtidspension eftersom de inte klarar av att utföra sina arbetsuppgifter. Nyckelord: Aktiviteter i dagliga livet, Arbetsterapi, Reumatoid artrit, RA, Smärta., Background: Rheumatoid arthritis (RA) is a progressive, chronic, and systemic autoimmune disease characterized by fluctuating symptoms such as pain, fatigue, and swollen joints. The disease can be relieved but not cured. RA is a public health problem, with the most common age of the outbreak being 40 years and older. Disease activity has a significant impact on affected individuals and their ability to perform daily activities. Many feel limited by pain. The experience of pain causes many individuals to become socially isolated, as they can no longer engage in the activities they find meaningful. Many are affected in their work, as the disease causes both pain and decreased hand strength. Aim: The aim of this study v is to map what previous research says about the impact of pain on daily activities in people with the diagnosis Rheumatoid Arthritis. Method: The study is a scoping review. The articles were produced in the databases Cinahl, Medline and PsycInfo. A total of 14 articles were included in the study. Results: The research results indicate that individuals with RA are limited in their daily activities due to pain. Despite this, many individuals choose to participate in different activities as a distraction from the pain. They find alternative ways to engage in occupations/activities. A supportive environment and permissive setting have been shown to have a positive impact on activity engagement and can reduce limitations. Conclusion: To live with RA can be a challenge and it is clear how pain limits people from engaging in activities that they consider meaningful and/or give them joy. This can contribute to social isolation and sometimes individuals are forced to take early retirement because they can not perform their work tasks anymore. Key words: Activities in daily life, Occupational therapy, Pain, Rheumatoid arthritis, RA.

La propuesta de TFM (Trabajo Final de Master) aquí planteado consiste en enfrontar a los alumnos del Ciclo Formativo de Grado Superior en Automatización Industrial y Robótica, a una situación real, con el objetivo de comprender mejor la problemática asociada. Para ello, se desarrollará una actividad basada en la metodología ABP (Aprendizaje Basado en Proyectos), que tiene como objetivo, entre otros, adquirir un aprendizaje significativo y perdurable, al mismo tiempo que potencia la motivación de los alumnos.

Objectives: To investigate the association between patient-physician discordance in the assessment of disease activity and residual US synovitis/tenosynovitis in a cohort of patients with RA in clinical remission. Methods: A post hoc analysis of the STARTER study, promoted by the Musculoskeletal-US (MSUS) Study Group of the Italian Society for Rheumatology, was performed using data from 361 consecutive patients with RA in clinical remission. The global assessment of disease activity by each patient (PGA) and evaluator/physician (EGA) was recorded on a 100-mm visual analogue scale. The PGA-EGA discordance was classified as positive (PGA>EGA) or negative (PGA

Les noves normatives de la Unió Europea, en relació amb la mobilitat urbana i les emissions contaminants, afavoreixen un entorn on les empreses poden innovar i deixar anar la seva creativitat en la recerca de tecnologies que ajudin a incrementar l'ús del transport públic urbà com a principal mitjà de transport pels habitants de les grans ciutats, que són també les més contaminants. Per veure com podem fomentar aquesta transició cap a una mobilitat més sostenible, proposem el disseny d'un entorn d'edició de continguts de Realitat Augmentada, on es podrà dissenyar un entorn augmentat a tota la xarxa de transport públic de la ciutat de Barcelona que li aporti un valor afegit, per tal de fer més senzilla pels usuaris la transició del transport privat al públic. Aquest entorn consta d'una aplicació web, on els dissenyadors de l'empresa encarregada de la seva gestió podran preparar els continguts augmentables que després seran disponibles a la xarxa de transport, i d'una aplicació mòbil, oberta al públic general, que serà la que permetrà als usuaris de la xarxa de transport metropolità consumir els continguts augmentats prèviament dissenyats a l'aplicació web. El repte principal al qual ens hem enfrontat al llarg del procés de desenvolupament del sistema ha estat principalment trobar la millor manera de detectar les marques de referència necessàries per poder mostrar el contingut de Realitat Augmentada a l'aplicació mòbil. Per solucionar-ho, s'ha optat per implementar un sistema addicional de detecció de caràcters, que ens servirà per detectar textos i mostrar el contingut associat. Aquest projecte ha estat possible gràcies a la col·laboració, dintre del marc d'un Conveni de Cooperació Educativa, de dues empreses: l'inLab FIB i l'Autoritat del Transport Metropolità de Barcelona. El Treball de Fi de Grau, per tant, ha estat realitzat en modalitat B, i tenia l'objectiu d'aportar un valor afegit a la Xarxa de Transport Metropolità mitjançant contingut augmentat disponible en, The new regulations of the European Union, in relation to urban mobility and polluting emissions, favor an environment where companies can innovate and unleash their creativity in the search for technologies that help increase the use of urban public transport as the main means of transport for the inhabitants of the big cities, which are also the most polluting. To see how we can encourage this transition towards a more sustainable mobility, we propose the design of an Augmented Reality Content Design Environment, where it will be possible to design an augmented environment throughout the public transport network of the city of Barcelona that provide added value, in order to make the transition from private to public transport easier for users. This environment consists of a web application, where the designers of the company in charge of its management will be able to prepare the augmentable contents that will then be available on the transport network, and a mobile application, open to the public, which will allow users of the metropolitan transport network to consume augmented content previously designed in the web application. The main challenge we faced throughout the system development process was mainly to find the best way to detect the necessary reference marks to be able to display the Augmented Reality content in the mobile application. To solve this, it has been decided to implement an additional text detection system, which will be used to detect texts and display the associated content. This project has been possible thanks to the collaboration, within the framework of an Educational Cooperation Agreement, of two companies: inLab FIB and the Autoritat del Transport Metropolità de Barcelona. This Final Project, therefore, has been carried out in mode B, and had the objective of bringing added value to the Metropolitan Transport Network through augmented content available in real time, which helps users to have more and better information while using th

Objective: This study is a sub-analysis from the patient cohort of the STARTER (Sonographic Tenosynovitis Assessment in RheumaToid arthritis patiEnts in Remission) study. The aim was to evaluate differences in ultrasound-detected joint and/or tendon involvement between patients receiving therapies based on a combination of conventional synthetic DMARDs (csDMARDs) and biologic DMARDs (bDMARDs) and those who were treated with either csDMARDs or bDMARDs in monotherapy. Material and methods: Four hundred and twenty-seven consecutive patients with a diagnosis of RA were recruited between October 2013 and June 2014. They were divided into three subgroups based on their therapy at baseline: patients with bDMARD in monotherapy, patients with csDMARD in monotherapy and patients in combination therapy (csDMARD + bDMARD). At baseline, 6 months and 12 months, a clinical examination (28 joint count) and an ultrasound evaluation were performed in each patient. A score of grey-scale (GS) and power Doppler (PD) synovitis and tenosynovitis was calculated based on the OMERACT scoring systems. Results: Two hundred and fifty-six patients completed the observation period: 48 patients from the bDMARD group (18.75%), 152 patients from the csDMARD group (59.38%) and 56 patients from csDMARD + bDMARD group (21.88%). The analysis showed that GS tenosynovitis and PD tenosynovitis are better controlled in combination therapy than they are ith csDMARD alone (P=0.025 and P=0.047, respectively); for PD synovitis, there was a better response in those who were treated with the combination therapy when compared with the patients receiving csDMARD (P=0.01) or bDMARD (P=0.02) alone. Conclusions: The analysis showed a lower prevalence of subclinical inflammatory manifestations detected with ultrasound imaging in those patients treated with the combination therapy than in those in monotherapy.

Objectives To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active RA who start (new) DMARD-therapy. Methods Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs because of active RA, and in whom treatment intensification according to the T2T principle was pursued, were assessed for disease activity every 3 months for 2 years (RA-BIODAM cohort). The primary outcome was the change in Sharp-van der Heijde (SvdH) score, assessed every 6 months. Per 3-month interval DAS44-T2T could be followed zero, one or two times (in a total of two visits). The relation between T2T intensity and change in SvdH-score was modelled by generalized estimating equations. Results In total, 511 patients were included [mean (S.D.) age: 56 (13) years; 76% female]. Mean 2-year SvdH progression was 2.2 (4.1) units (median: 1 unit). A stricter application of T2T in a 3-month interval did not reduce progression in the same 6-month interval [parameter estimates (for yes vs no): +0.15 units (95% CI: −0.04, 0.33) for 2 vs 0 visits; and +0.08 units (−0.06; 0.22) for 1 vs 0 visits] nor did it reduce progression in the subsequent 6-month interval. Conclusions In this daily practice cohort, following T2T principles more meticulously did not result in less radiographic progression than a somewhat more lenient attitude towards T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome., Objectives: To investigate whether meticulously following a treat-To-Target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active RA who start (new) DMARD-Therapy. Methods: Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs because of active RA, and in whom treatment intensification according to the T2T principle was pursued, were assessed for disease activity every 3 months for 2 years (RA-BIODAM cohort). The primary outcome was the change in Sharp-van der Heijde (SvdH) score, assessed every 6 months. Per 3-month interval DAS44-T2T could be followed zero, one or two times (in a total of two visits). The relation between T2T intensity and change in SvdH-score was modelled by generalized estimating equations. Results: In total, 511 patients were included [mean (s.d.) age: 56 (13) years; 76% female]. Mean 2-year SvdH progression was 2.2 (4.1) units (median: 1 unit). A stricter application of T2T in a 3-month interval did not reduce progression in the same 6-month interval [parameter estimates (for yes vs no): +0.15 units (95% CI:-0.04, 0.33) for 2 vs 0 visits; and +0.08 units (-0.06; 0.22) for 1 vs 0 visits] nor did it reduce progression in the subsequent 6-month interval. Conclusions: In this daily practice cohort, following T2T principles more meticulously did not result in less radiographic progression than a somewhat more lenient attitude towards T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome.

OBJECTIVES: Clinical trials have shown that low-dose glucocorticoid therapy in patients with rheumatoid arthritis (RA) reduces bone loss in hands or hip, but the effect on osteoporotic fractures is not yet clear. Therefore, we investigated the use of low-dose oral glucocorticoids and risk of osteoporotic fractures among patients with RA.METHODS: This was a cohort study including patients with RA aged 50+ years from the Clinical Practice Research Datalink between 1997-2017. Exposure to oral glucocorticoids was stratified by the most recent prescription in current (<6 months), recent (7-12 months), and past (>1 year) use, and average daily and cumulative doses. Risk of incident osteoporotic fractures (including hip, vertebrae, humerus, forearm, pelvis, and ribs) were estimated by time-dependent Cox proportional-hazards models, adjusted for life-style parameters, comorbidities, and comedications. Secondary analyses assessed osteoporotic fracture risk with a combination of average daily and cumulative doses of oral glucocorticoids.RESULTS: Among 15 123 patients with RA (mean age 68.8 years, 68% females), 1640 osteoporotic fractures occurred. Current low-dose oral glucocorticoid therapy (≤7.5 mg prednisolone equivalent/day) in patients with RA was not associated with overall risk of osteoporotic fractures (adjusted hazard ratio 1.14, 95% CI 0.98-1.33) compared with past glucocorticoid use, but was associated with an increased risk of clinical vertebral fracture (adjusted hazard ratio 1.59, 95% CI 1.11-2.29). Results remained unchanged regardless of a short-term or a long-term use of oral glucocorticoids.CONCLUSION: Clinicians should be aware that even in RA patients who receive low daily glucocorticoid doses, the risk of clinical vertebral fracture is increased.

Introduction - Unacceptable delays in providing services by the Regional Director of Health Services’ Office, Kurunegala and subsequent re-visits had created customer dissatisfaction. A citizen’s charter and supplementary interventions were developed and implemented to improve providing services. The objective of this study is to assess effectiveness of implementing citizen’s charter and supplementary interventions at Establishment Branch of Regional Director of Health Services’ Office, Kurunegala.Methods - Methods involve developing process and outcome indicators to assess the effectiveness of charter and supplementary interventions, pre and post-assessments of developed indicators following implementing interventions for three months, and comparison of pre and post results for statistical significance to assess the effectiveness of implementations.Results - Following implementations, compliance of personal files with service standards significantly increased (p<0.001) from 40% to 94% while average number of visits per service to Establishment Branch had a significant reduction (p<0.001) from 2.40 to 1.09. Nursing officers’ overall satisfaction on receiving services improved significantly (p<0.001) from 11.5% to 75% as their satisfaction on all service attributes showed statistically significant improvements. Three attributes namely, awareness of place of formats, availability of contact details of responsible officer for services and courtesy exceeded expectations although the remainder showed expectation-perception gaps.Conclusion - Charter and supplementary interventions proved to be effective in improving service provision at Establishment Branch of Regional Director of Health Services’ Office, Kurunegala. It is recommended that Regional Director of Health Services’ offices implement charters and supplementary interventions at Establishment Branches in a stepwise manner to improve service provision.

Objective: To quantify preferences for preventive therapies for rheumatoid arthritis (RA) across three countries. Methods: A web-based survey including a discrete choice experiment was administered to adults recruited via survey panels in the UK, Germany and Romania. Participants were asked to assume they were experiencing arthralgia and had a 60% chance of developing RA in the next 2 years and completed 15 choices between no treatment and two hypothetical preventive treatments. Treatments were defined by six attributes (effectiveness, risks and frequency/route of administration) with varying levels. Participants also completed a choice task with fixed profiles reflecting subjective estimates of candidate preventive treatments. Latent class models (LCMs) were conducted and the relative importance of attributes, benefit–risk trade-offs and predicted treatment uptake was subsequently calculated. Results: Completed surveys from 2959 participants were included in the analysis. Most participants preferred treatment over no treatment and valued treatment effectiveness to reduce risk more than other attributes. A five-class LCM best fitted the data. Country, perceived risk of RA, health literacy and numeracy predicted class membership probability. Overall, the maximum acceptable risk for a 40% reduction in the chance of getting RA (60% to 20%) was 21.7%, 19.1% and 2.2% for mild side effects, serious infection and serious side effects, respectively. Predicted uptake of profiles reflecting candidate prevention therapies differed across classes. Conclusion: Effective preventive pharmacological treatments for RA were acceptable to most participants. The relative importance of treatment attributes and likely uptake of fixed treatment profiles were predicted by participant characteristics., IMI-PREFER

Globally, sweetpotato (Ipomoea batatas (L.) Lam) or kumala is regarded as an essential, versatile, and under-utilised food security crop. In Fiji, kumala has a strong traditional base, and our ancestors valued this crop as a lifesaver to people during and after natural disasters to act as food security since both the tubers and leaves are consumed. This research weaves together two methodologies; the Fijian Vanua Research Framework (FVRF) which involves ethnobotany studies, and a western sciences (field trials) research element to support and reinstruct smallholder farmers on the value of kumala as a significant crop for subsistence and a source of livelihood for rural economic development in Fiji. The three research sites were Nabukadra (<20m asl ) located in the coastal land area, Bucalevu (>150m asl) in the high altitude inland, and Burenitu (80-100m asl) in the district of Nalawa which is situated at a lower altitude. The implementation of FVRF in this research paid specific attention to indigenous Fijian society aligning to future food security issues in an agricultural context. This research sought a solidarity approach for the rural areas in Fiji adopting their systems of knowledge and perception as the basis for inquiry extending the knowledge base of indigenous people and transforming their understanding of the social-cultural world like solesolevaki, which is our current cultural currency. The Dre’e metaphor was generated to discuss the findings from this research. The findings of this research discussed the cultural role of kumala production in the I-Taukei context under four components: values and beliefs, practices, skills, and knowledge. Indigenous Knowledge (IK) exists across all facets of the I-Taukei way of life, which includes health, belief system, and environmental survival. Given that each genotype or variety of kumala may respond differently to production factors, there was a need to evaluate available sweetpotato genotypes across geographic zo

Objectives Pulmonary manifestations in RA are common comorbidities, but the underlying mechanisms are largely unknown. The added value of a multiplex of ACPA and genetic risk markers was evaluated for the development of pulmonary fibrosis (PF) in an inception cohort. Methods A total of 1184 patients with early RA were consecutively included and followed prospectively from the index date until death or 31 December 2016. The presence of 21 ACPA fine specificities was analysed using a custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden). Three SNPs, previously found related to PF were evaluated, rs2609255 (FAM13A), rs111521887 (TOLLIP) and rs35705950 (MUC5B). ACPA and genetic data were available for 841 RA patients, of whom 50 developed radiologically defined PF. Results In unadjusted analyses, 11 ACPA specificities were associated with PF development. In multiple variable analyses, six ACPA specificities were associated with increased risk of PF: vimentin (Vim)60-75, fibrinogen (Fib)beta 62-78 (72), Fib alpha 621-635, Bla26, collagen (C)II359-369 and F4-CIT-R (P < 0.01 to P < 0.05). The number of ACPA specificities was also related to PF development (P < 0.05 crude and adjusted models). In multiple variable models respectively adjusted for each of the SNPs, the number of ACPA specificities (P < 0.05 in all models), anti-Vim60-75 (P < 0.05, in all models), anti-Fib beta 62-78 (72) (P < 0.001 to P < 0.05), anti-CII359-369 (P < 0.05 in all models) and anti-F4-CIT-R AQ4 (P < 0.01 to P < 0.05), anti-Fib alpha 621-635 (P < 0.05 in one) and anti-Bla26 (P < 0.05 in two) were significantly associated with PF development. Conclusion The development of PF in an inception cohort of RA patients was associated with both presence of certain ACPA and the number of ACPA specificities and risk genes.

Objectives: To investigate the appropriate timing, useful findings and combination of magnetic resonance imaging (MRI) and ultrasound (US) for predicting the radiographic progression in early rheumatoid arthritis (RA). Methods:Forty-four active RA patients, who examined by both of MRI and US in the symptomatic wrist and finger joints, were recruited in Nagasaki University Hospital from 2010 to 2017 and treated by the treat-to-target therapeutic strategy for 1 year. MRI was evaluated by RA MRI scoring and US by Outcomes Measures in Rheumatology Clinical Trial, respectively. Plain radiographs were assessed by the Genant-modified Sharp score for the symptomatic side in the same manner as MRI and US. Radiographic progression was defined as an annual increase ≥0.75 at 1 year. Factors associated with radiographic progression were analysed. Also, the optimal combination of MRI and US at each timepoint was considered. Results:Logistic regression model revealed that MRI-proven bone marrow oedema at baseline and 6 months and joint counts of power-Doppler grade ≥2 articular synovitis at 3 or 6 months were significantly associated with radiographic progression at 1 year. Conclusion:This study may suggest the favourable timing and combination of MRI and US at each point to predict radiographic progression in patients with early-stage RA., Modern rheumatology, 33(4), pp.708-714; 2023

Background Patients with hypertrophic scars (HTS) risk reduced quality of life due to itching, pain, poor cosmesis, and restriction of movement. Despite good clinical efficacy, patients are often reluctant to undergo repeated needle injections due to pain or needle phobia. Objectives To evaluate the applicability of needle-free pneumatic jet injection (PJI) and assess changes in hypertrophic scars following a single PJI treatment with 5-fluorouracil (5-FU) and triamcinolone acetonide (TAC). Methods Twenty patients completed this blinded, randomized, controlled, split-scar trial. The intervention side of the HTS received a one-time treatment with PJIs containing a mixture of TAC + 5-FU injected at 5 mm intervals (mean 7 PJI per HTS); the control side received no treatment. Assessments were made at baseline and 4 weeks posttreatment. Outcome measures included change in (1) Vancouver Scar Scale (VSS) total score and subscores, (2) scar volume and surface area assessed by three-dimensional imaging, (3) skin microarchitecture measured by optical-coherence tomography (OCT), (4) photo-assessed scar cosmesis (0-100), (5) patient-reported pain and satisfaction (0-10), and (6) depiction of drug biodistribution after PJI. Results PJI with TAC + 5-FU significantly decreased both HTS height (-1 VSS; p = 0.01) and pliability (-1 VSS; p < 0.01) with a nonstatistically significant reduction of -1 in total VSS score (0 in control; p = 0.09). On 3D imaging, a 33% decrease in scar volume (p = 0.016) and a 37% decrease in surface area (p = 0.008) was observed. OCT indicated trends towards smoother scar surface (Ra 11.1-10.3; p = 0.61), normalized dermal microarchitecture (attenuation coefficient: 1.52-1.68; p = 0.44), and a reduction in blood flow between 9% and 17% (p = 0.50-0.79). Despite advances in VSS subscores and OCT, no improved photo-assessed cosmesis was found (-3.2 treatment vs. -1.4 control; p = 0.265). Patient-reported pain was low (2/10) and 90% of the patients that

This essay analyzes, from Transmedia Narrative perspectives the proposal of Henry Jenkins (2008) and Carlos Scolari (2012), the incipient joining between the book, –understood as a classic support of reading text– and Augmented Reality (AR). This AR-book is exposed as a new communicational product in the Digital Editorial Design field, which calls into question the classic conception of a single author, usually the writer, giving the digital designer a significant importance in the narrative construction as a co-authorship. The AR-Book does not deny the physicality of the object-book, but rather complements it through the user experience and Transmedia Narratives. This add-on is able due to the emergence of mobile devices, leading the reader to immersive experiences, given by interactivity, geolocation, multimedia and visualization. Finally, this essay searches to underline a contrast between AR-books and Editorial Illustration process done by book designer Professor Guto Lins from his rational and narrative speech perspective during the books publishing., Este ensaio analisa, a partir da perspectiva de Narrativas Transmedia, proposta por Henry Jenkins (2008) e Carlos Scolari (2012), a incipiente união entre o livro, - en-tendido como suporte clássico para o texto de leitura - e a Realidade Aumentada (AR). O AR-Books é apresentado como um novo produto comunicacional no campo do Design Editorial Digital, que desafia a concepção clássica de um único autor, tradicionalmente o escritor, entregando ao designer digital um peso significativo na narrativa, construin-do um olhar de co-autoria. O AR-Books não abandona a fisicalidade do objeto livro, se-não o complementa através da experiência do usuário e o as Narrativas Transmedia. Este adendo sucede devido à irrupção de dispositivos móveis, levando o leitor a experiências imersivas, facilitadas pela interatividade, geolocalização, multimídia e visualização. Final-mente, o ensaio busca realizar um contraste entre os AR-Books e a produção de Ilustração Editorial trabalhada pelo designer e acadêmico Guto Lins desde sua perspectiva racional e discurso narrativo no processo de edição., Este ensayo analiza, desde la perspectiva de Narrativas Transmedia, propuesta por Henry Jenkins (2008) y Carlos Scolari (2012), la incipiente unión entre el libro, –entendido como soporte clásico del texto de lectura– y la Realidad Aumentada (RA). El Libro-RA se expone como un nuevo producto comunicacional en el campo del Diseño Editorial Digital, que desafía la clásica concepción de un único autor, tradicionalmente el escritor, entregando al diseñador digital un peso significativo en la narrativa construyendo una mirada de coautoría. El Libro-RA no abandona la fisicidad del objeto libro, sino que lo complementa a través de la experiencia de usuario y las Narrativas Transmedia. Este aditamento sucede debido a la irrupción de los dispositivos móviles, llevando al lector a experiencias inmersivas, facilitadas por la interactividad, geolocalización, multimedia, y visualización. Finalmente, el ensayo busca realizar un contraste entre los Libros-RA y la producción de Ilustración Editorial trabajada por el diseñador y académico Guto Lins desde su perspectiva racional y discurso narrativo en el proceso de edición.

OBJECTIVE: We aimed to systematically review the literature to retrieve evidence on the diagnostic and prognostic value of musculoskeletal ultrasound for a treat to target (T2T) approach in RA. METHODS: Eight research questions were developed addressing the role of ultrasound (including different ultrasound scores and elementary lesions) for diagnosis, monitoring and prognosis of RA. PubMed and EMBASE were searched (2005-2020). Articles on RA and reporting data on musculoskeletal ultrasound were included and extracted according to the underlying questions, and risk of bias assessed according to the study design. RESULTS: Out of 4632 records, 60 articles were included. Due to clinical heterogeneity, meta-analysis was not possible. Ultrasound better predicted disease relapses with respect to clinical examination in patients in remission, while both methods performed similarly in predicting response to therapy, achievement of remission and radiographic progression. Ultrasound was superior to clinical examination in diagnosing joint involvement using another imaging modality, such as magnetic resonance imaging, as reference. Limited ultrasound scores performed like more extensive evaluations for the detection of joint inflammation and for outcome prediction. Higher ultrasound scores of synovitis were linked to poor outcomes at all disease stages, but a specific cut-off distinguishing between low- and high-risk groups did not emerge. CONCLUSIONS: These data confirm the pivotal role of ultrasound when evaluating synovial inflammation and when identifying RA patients at higher risk of relapse. Further research is needed to better define the role of ultrasound in a T2T management strategy in moderately-to-highly active RA.

OBJECTIVES: To develop and validate in real-world patients a conversion algorithm from the Multidimensionel Health Assessment Questionnaire physical function scale (MDHAQ) to the Stanford Health Assessment Questionnaire disability index physical function scale (HAQ) score. METHODS: From the DANBIO registry, 13 391 patients with RA (n = 8983), PsA (n = 2649) and axial spondyloarthritis (axSpA, n = 1759) with longitudinal data on HAQ and MDHAQ were included, stratified by diagnosis, and randomized 1:1 into development and validation cohorts. Conversion algorithms were developed by linear regression and applied in validation cohorts. From MDHAQ, the HAQ was calculated (cHAQ) and validated against the observed HAQ for criterion, correlational and construct validity. RESULTS: For RA, we developed the conversion algorithm cHAQ = 0.15+MDHAQ*1.08, and validated it in the RA validation cohort. Criterion validity: HAQ and cHAQ had comparable discriminative power to distinguish between high and low patient global scores (standardized mean difference: HAQ:-1.29, cHAQ:-1.35). Kappa value between HAQ and cHAQ functional states indicated good agreement (0.83). Correlational validity: baseline HAQ and cHAQ, respectively, correlated well with patient global scores (r = 0.65/0.67). Bland-Altman plots showed good agreement across all functional states. Construct validity: HAQ and cHAQ discriminated equally well between patients reporting symptom state as acceptable vs not, and across responses to an external anchor. Aiming for a common algorithm, the RA conversion algorithm was validated for PsA and axSpA with similar results. CONCLUSION: This study suggests that in observational datasets with only the MDHAQ available, a simple algorithm allows valid conversion to HAQ on the group level in RA, PsA and axSpA.

Background: Rheumatoid arthritis (RA) is a disease with a great impact on all aspects of life. Living with RA affects patients’ health including physical, emotional, psychological, and social aspects. Patients with RA are treated with disease-modifying anti-rheumatic drugs (DMARDs) and monitored with tight control to achieve low disease activity or remission. Nevertheless, RA can be life-changing when the patients need long-term treatment to control the disease activity. The goal of treatment for patients with chronic diseases such as RA is to achieve optimal health and a life as normal as possible. It is therefore important to gain knowledge about how patients experience everyday life a short period after the initiation of DMARD treatment. Aim: To describe patients’ experiences of living with RA after 1-2 years of DMARD treatment. Methods: The study has a qualitative design with an inductive approach. Focus groups (n=17) and individual (n=5) interviews were conducted with 22 patients with RA. The participants consisted of 15 women and 7 men with a mean age of 57 years and a disease duration of 12-21 months. The participants were treated with conventional or biological DMARDS for 12-20 months. The main questions were: “Can you tell me how RA impacts your daily life?” “Which outcomes of your RA are important to you at this moment?“ The interviews were analyzed with qualitative content analysis and five categories with an overarching theme emerged (Table 1). Results: Patients’ experiences of living with RA after 1-2 years of DMARD treatment lead to new insights into life and were expressed as 1) Surrendering to disease limitations due to being restricted by pain, fatigue, and in function; 2) Adapting to disease limitations by adjusting one´s work balance and one’s social life; 3) Transitioning in self-identity due to disease limitations by not recognising oneself and experiencing a change of bodily appearance and mood; 4) Fighting disease limitations by experiencing

ObjectivesConcern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA.MethodsWe performed a new-user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and USA). RA patients ≥18 years of age and initiating HCQ were compared with those initiating SSZ (active comparator) and followed up in the short (30 days) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HRs), with estimates pooled where I2 <40%.ResultsA total of 918 144 and 290 383 users of HCQ and SSZ, respectively, were included. No consistent risk of psychiatric events was observed with short-term HCQ (compared with SSZ) use, with meta-analytic HRs of 0.96 (95% CI 0.79, 1.16) for depression, 0.94 (95% CI 0.49, 1.77) for suicide/suicidal ideation and 1.03 (95% CI 0.66, 1.60) for psychosis. No consistent long-term risk was seen, with meta-analytic HRs of 0.94 (95% CI 0.71, 1.26) for depression, 0.77 (95% CI 0.56, 1.07) for suicide/suicidal ideation and 0.99 (95% CI 0.72, 1.35) for psychosis.ConclusionHCQ as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation or psychosis compared with SSZ. No effects were seen in the short or long term. Use at a higher dose or for different indications needs further investigation.Trial registrationRegistered with EU PAS (reference no. EUPAS34497; http://www.encepp.eu/encepp/viewResource.htm? id=34498). The full study protocol and analysis source code can be found at htt

The history of readers’ advisory services is both valuable and misinterpreted. Examining the practices and motivations in the implementation of readers’ advisory in the 1920s-1930s points to marked differences and subtle similarities to the readers’ advisory services we know today. Delving into historically and culturally significant events during this time period points to education as the main priority and purpose of RA.

Rheumatoid arthritis (RA) is an autoimmune disease, which causes joint inflammation. Different environmental and genetic factors such as smoking, anti-citrullinated protein antibody, rheumatoid factor, and certain MHC-alleles cause RA. It affects mostly women and it is characterised by joint swelling, pain, tiredness, and stiffness. Untreated RA can lead to disability and complications in different organs (brain, lung, heart,). The body develops tolerance against self-antigens using different mechanisms, including Tregs mediated, by increasing the expression of inhibitory receptors and through receptor modification/destruction of self-reactive cells. Failure in the resistance development mechanism leads to autoimmune diseases. The most important cellular components of RA dependent inflammation are macrophages, T-cells, and B-cells. These cells contribute to the inflammations process by producing antibodies, cytokines, and through antigen presentation or immune cell activation. One of the cytokines, which are released by macrophages and T-cells is Tumour necrosis factor (TNF). It stimulates angiogenesis, activation of osteoclasts and the production of different cytokines by increasing the expression of NF-kB. The diagnostic process of RA consists of serological, physical, and radiological examinations. These examinations together with other factors are utilized for calculating score (0-10), in order to decide if a patient have RA or not. The treatment of RA depends on disease activity and it is composed of NSAID, steroids, DMARDs, biological DMARDs and non-pharmacological treatment. The interventions can be given as a monotherapy or in combination. The disease activity of RA or the efficacy of a drug which is used to treat RA can be studied by ACR response, DAS-28, HAQ-DI score using joint progression score. The aim of the study was to investigate the efficacy and safety of adalimumab, as well as to compare it with other treatments, which are used to in RA. 5 scien

Introduktion/bakgrund: Reumatoid artrit (RA) är en autoimmun sjukdom som angriper leder. Mellan 0,5–1% av befolkningen i Sverige är drabbade av RA. Sjukdomen går inte att bota, bara lindra. Syfte: Med studien är att beskriva livskvalité hos patienter med RA. Metod: En icke systematisk litteraturstudie. Resultat: Resultatet baseras på elva vetenskapliga artiklar. Utifrån artiklarna kodas kategorier vilka påverkar patienter med RA på olika sätt. Fysisk och psykisk påverkan, lägre och ökad grad av livskvalité. Patienter med RA förenas genom att sjukdomen påverkar livskvalité. Det som påverkar patienter med RA till lägre grad av livskvalité är, smärta, fatigue/sömn och depression. Depression är ett vanligt symtom hos patienter med RA. Även känslan av att vara beroende av närstående i vardagen ger en lägre grad av livskvalité. Ökad grad av livskvalité får patienter med RA genom att känna delaktighet på arbete eller i en gemenskap, samt att ha närstående runt sig med god förståelse. Patienter med RA som får stöd från omgivningen eller psykolog upplever ökad grad av livskvalité. Slutsats: Att leva med sjukdomen orsakar lidande för patienter med RA, både privat och i arbetslivet. Sjukdomen påverkar både fysiskt och psykiskt och det är viktigt att komma under behandling för symtom snarast möjligt för att inte få lägre grad av livskvalité.

Primary cardiac angiosarcomas are rare malignant tumors with a very poor prognosis. We present a case of a 48-year-old man with no previous cardiac history who developed an incessant focal atrial tachycardia complicated by tachycardia-mediated cardiomyopathy as a consequence of cardiac angiosarcoma. (Level of Difficulty: Beginner.).

OBJECTIVES: To explore the impact of the COVID-19 pandemic on treat-to-target strategies (disease activity, remission rates) and access to physical consultations in patients with inflammatory rheumatic disease, as well as to explore characteristics of patients with/without physical consultations in the clinic and the impact of early vs established disease. METHODS: Patients with RA, PsA or axial SpA (axSpA) prospectively followed in the nationwide DANBIO registry answered online questionnaires and reported patient-reported outcomes (PROs) in June and November 2020. Patient characteristics, disease activity and physical consultations in the clinic before and during the pandemic were identified in DANBIO [all patients and subgroups with early disease (disease duration ≤2 years)]. In individual patients, changes in PROs before and during the pandemic were calculated. Characteristics of patients with/without physical consultations were described (age, gender, education level, comorbidities, disease duration, treatment). RESULTS: We included 7836 patients (22% of eligible patients), 12% of which had early disease. PROs were stable before and during the pandemic, with median changes approximating zero, as well as in patients with early disease. Remission rates were stable. The relative decrease in the number of patients with physical consultations was 21-72%, which was highest in axSpA. Characteristics of patients with/without physical consultations were similar. Self-reported satisfaction with treatment options and access was >70%; the preferred contact form was physical consultation (66%). CONCLUSION: In this nationwide study performed during the first 8 months of the pandemic, patient satisfaction was high and the PROs and remission rates remained stable despite the remarkable reduction in physical consultations, as well as in patients with early disease. Characteristics of patients with/without physical consultations appeared similar.

Objective: To assess the prevalence of tuberculin skin test (TST) positivity in early rheumatoid arthritis patients (< 6months disease duration) using Tuberculin sensitivity testing in a TB endemic country. Method: Included in this cross-sectional study were 200 patients of early rheumatoid arthritis divided into three groups- treatment naïve, patients on methotrexate only and methotrexate plus low dose corticosteroids. Results: 200 early RA patients and 60 healthy controls were included in this study. The median age of the study population was 43 years (IQR 33-51) with a mean disease duration of 3.4 ± 2.1 months. 54 patients (27%) with early RA and 22 healthy control (36.7%) had TST positive (p=0.1). Conclusion: Tuberculin positivity is low among patients with early RA as compared to the general population. The use of low dose steroids or methotrexate doesn’t affect the tuberculin anergy.

Магістерська дисертація викладена на 83 сторінках, літературних джерел 37, серед них 4 іноземних; рис. 2, табл. 11. Актуальність теми. Ревматоїдний артрит – є одним з найпоширеніших запальних хвороб суглобів, що завдає значну як фізичну, психічну та соціально-економічну шкоду хворим. На сьогоднішній день хвороби ревматоїдного походження залишаються найбільш поширеними патологіями в світі, в Україні зокрема. З кожним роком з’являється велика кількість сучасних засобів, які доцільно включати до програми фізичної терапії. Все викладене вище визначає актуальність та необхідність подальшого вивчення данного питання у відновленні пацієнтів при ревматоїдному артриті, що і стало підставою для виконання цієї магістерської дисертації. Зв’язок роботи з науковими програмами, планами, темами. Магістерська дисертація виконана відповідно до наукової тематики кафедри біобезпеки і здоровя людини НТУУ «КПІ ім. Сікорського». Мета роботи: розробити програми фізичної терапії при ревматойдному артриті та оцінити її ефективність. Завдання: за даними спеціальної літератури вивчити сучасний стан і напрямки вдосконалення програми фізичної терапії при ревматойдному артриті; дослідити функціональний стан суглобів; розробити програму фізичної терапії при ревматойдному артриті та перевірити її ефективність. Об’єкт дослідження –хворі на ревматойдний артрит. Предмет дослідження – фізична реабілітація хворих на ревматойдний артрит. Методи дослідження: аналіз спеціальної науково-методичної літератури та інформаційних джерел; клінічні методи дослідження (контент-аналіз історій хвороби, огляд); візуально-аналогова шкала болю (VAS); інструментальні методи дослідження та методи математичної статистики. Наукова новизна одержаних результатів: вивчені функціональні особливості суглобів у хворих на ревматойдний артрит, що відкрило можливості для розробки програми фізичної терапії; визначені особливості змісту та спрямованості програми фізичної терапії, підібрані засоби відновлення з урахуванням ступеня функ, The master's dissertation is presented on 83 pages, literary sources 37, among them 4 foreign; Fig. 2, table. 11, Annex 1. Actuality of theme. Rheumatoid arthritis is one of the most common inflammatory diseases of the joints, which causes significant physical, mental and socio-economic damage to patients. Today, diseases of rheumatoid origin remain the most common pathologies in the world, in Ukraine in particular. Every year there are a large number of modern tools that should be included in the physical therapy program. All of the above determines the relevance and need for further study of this issue in the recovery of patients with rheumatoid arthritis, which became the basis for this master's thesis. Connection of work with scientific programs, plans, topics. The master's dissertation is made in accordance with the scientific theme of the Department of Biosafety and Human Health NTUU "KPI. Sikorsky ». Purpose: to develop physical therapy programs for rheumatoid arthritis and evaluate its effectiveness. Objectives: according to the special literature to study the current state and areas of improvement of physical therapy for rheumatoid arthritis; to investigate the functional state of the joints; develop a program of physical therapy for rheumatoid arthritis and test its effectiveness. The subject of the study is patients with rheumatoid arthritis. The subject of research - physical rehabilitation of patients with rheumatoid arthritis. Research methods: analysis of special scientific and methodical literature and information sources; clinical research methods (content analysis of case histories, review); visual-analog pain scale (VAS); instrumental research methods and methods of mathematical statistics. Scientific novelty of the obtained results: the functional features of the joints in patients with rheumatoid arthritis were studied, which opened opportunities for the development of a physical therapy program; the peculiarities of the content and direction of

Objective:To evaluate the biological effect and mechanisms of C-reactive protein (CRP) on the activation of fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). Study design:To understand if CRP is involved in RA, expression of CRP and its receptors CD32/64 was examined in synovial tissues from RA patients and normal controls.In vitro, the potential role and mechanisms of CRP in FLS proliferation and invasion, expression of pro-inflammatory cytokines, and activation of signaling pathways were investigated in both RA - FLS and a normal human fibroblast-like synoviocyte line (HFLS). Results:Compared to normal controls, synovial tissues from 21 RA patients exhibited highly activated CRP signaling, particularly by FLSs as identified by 65% of CRP-expressing cells being CRP+vimentin+ and CD32/64+vimentin+ cells.In vitro, FLSs from RA patients, but not HFLS, showed highly reactive to CRP by largely increasing proliferative and invasive activities and expressing pro-inflammatory cytokines and chemokines, including CCL2, CXCL8, IL-6, and MMP2/9. All these changes were blocked largely by a neutralizing antibody to CD32 and, to a less extent by the anti-CD64 antibody, revealing CD32 as a primary mechanism of CRP signaling during synovial inflammation. Further studies revealed that CRP also induced synovial inflammation differentially via CD32/CD64- NF-kappa B or p38 pathways as blockade of CRP-CD32-NF-kappa B signaling inhibited CXCL8, CCL2, IL-6, whereas CRP induced RA-FLS invasiveness through CD32-p38 and MMP9 expression via the CD64-p38-dependent mechanism. Conclusions:CRP signaling is highly activated in synovial FLSs from patients with RA. CRP can induce synovial inflammation via mechanisms associated with activation of CD32/64-p38 and NF-kappa B signaling.

Tipifarnib is a potent and highly selective inhibitor of farnesyltransferase (FTase). FTase catalyzes the posttranslational attachment of farnesyl groups to signaling proteins that are required for localization to cell membranes. Although all RAS isoforms are FTase substrates, only HRAS is exclusively dependent upon farnesylation, raising the possibility that HRAS-mutant tumors might be susceptible to tipifarnib-mediated inhibition of FTase. Here, we report the characterization of tipifarnib activity in a wide panel of HRAS-mutant and wild-type head and neck squamous cell carcinoma (HNSCC) xenograft models. Tipifarnib treatment displaced both mutant and wild-type HRAS from membranes but only inhibited proliferation, survival, and spheroid formation of HRAS-mutant cells. In vivo, tipifarnib treatment induced tumor stasis or regression in all six HRAS-mutant xenografts tested but displayed no activity in six HRAS wild-type patient-derived xenograft (PDX) models. Mechanistically, drug treatment resulted in the reduction of MAPK pathway signaling, inhibition of proliferation, induction of apoptosis, and robust abrogation of neovascularization, apparently via effects on both tumor cells and endothelial cells. Bioinformatics and quantitative image analysis further revealed that FTase inhibition induces progressive squamous cell differentiation in tipifarnib-treated HNSCC PDXs. These preclinical findings support that HRAS represents a druggable oncogene in HNSCC through FTase inhibition by tipifarnib, thereby identifying a precision therapeutic option for HNSCCs harboring HRAS mutations.

El presente proyecto de innovación acomete una nueva forma de entender el espacio geométrico básico de forma mucho más intuitiva, a través de la utilización de las Nuevas Tecnologías de la Información y Comunicación que cada vez más, se están popularizando dentro de nuestra propia vida cotidiana. En este sentido, la educación se debe de nutrir de los avances y beneficiarse de las posibilidades que ofrecen estas nuevas tecnologías. La Realidad Aumentada ofrece al interlocutor una experiencia visual con la cual se puede interactuar, a través de nuestra propia perspectiva visual. Precisamente es el propio entendimiento de nuestro entorno físico, el que sin duda, más cuesta de ser razonado por el alumnado. El paso que reforzaremos a través de esta tecnología será, el entendimiento tridimensional y la ubicación en su entorno próximo. De esta manera conseguiremos que el alumnado, esté motivado a través del uso de dispositivos electrónicos con aplicaciones y uso de software que podrán utilizar, en la asignatura de Educación Plástica Visual y Audiovisual o en Dibujo Técnico. A lo largo de este Trabajo Fin de Máster podremos ver cómo aplicar esta tecnología en el aula, cómo funciona e interactúan con ellas, qué posibilidades ofrece para actuar de forma interdisciplinar en la Educación Secundaria, y de esta manera introducir el complejo campo del Sistema Diédrico a través de la Realidad Aumentada.

[EN] Special Section Preface, [ES] Prefacio de la Sección Especial

We address the verification of concurrent programs running under the release-acquire (RA) semantics. We show that the reachability problem is undecidable even in the case where the input program is finite-state. Given this undecidability, we follow the spirit of the work on context-bounded analysis for detecting bugs in programs under the classical SC model, and propose an under-approximate reachability analysis for the case of RA. To this end, we propose a novel notion, called view-switching, and provide a code-to-code translation from an input program under RA to a program under SC. This leads to a reduction, in polynomial time, of the bounded view-switching reachability problem under RA to the bounded context-switching problem under SC. We have implemented a prototype tool VBMC and tested it on a set of benchmarks, demonstrating that many bugs in programs can be found using a small number of view switches.

Introduktion: RA är en progressiv sjukdom och behandlingen fokuserar på att lindra symtom. Sjukdomen förekommer i alla åldrar, men är vanligast hos de som är 40 år och äldre. Att lära sig att leva med sjukdomen kan vara mycket utmanande för patienter anhöriga. Hjälp av hälso- och sjukvården för att hantera sjukdomen och de problem som sjukdomen medför. Syfte: Litteraturstudien syftar till att belysa patienters upplevelse av att leva med RA. Metod: Litteraturstudien är baserad på Polit & Beck (2017) nio steg. Insamling av data utfördes i CINAHL & PubMed. Artiklarna som ingår kvalitetsgranskades enligt Polit & Beck (2017) granskningsmallar. Detta resulterade i totalt 10 artiklar, fyra kvalitativa, fem kvantitativa och en med mixad metod. Resultat: Resultatet presenteras i två huvudkategorier med två underkategori i varje. Den första huvudkategorin fick namnet ”Påverkan på livet” med underkategorierna "Begränsningar i privatlivet" och "Svårigheter i arbetslivet". Den andra huvudkategorin fick namnet ”Variation av stöd” med underkategorierna "Stöd från omgivningen" och "Icke-stöd från omgivningen". Slutsats: RA påverkar hela livet för den drabbade, både inom yrkeslivet, fritiden, socialt och i vardagen. RA ger upphov till svårigheter att leva ett normalt liv. Symtom som smärta, stelhet och trötthet påverkar patientens förmåga att utföra arbete, bedriva ADL och hushållssysslor samt upprätthålla en god relation till sin partner och familj. Förståelse och stöd från familjen ansågs vara värdefullt för att handskas med sjukdomen. Patienter efterfrågade mer emotionellt stöd från hälso- och sjukvården

Studien är ett samarbete med badrumsföretaget SVEDBERGS. Syftet med denna studie är att ge rekommendationer till SVEDBERGS kunder avseende färgtemperatur som är lämpligast i badrummet. I badrummet sker det olika aktiviteter som sminkning/rakning eller bad, därför är det viktigt att kunna anpassa belysningen för att bidra med en bra komfort till användarna. Med LED-ljuskällan finns det möjlighet att reglera färgtemperaturer i detalj. Denna studie kommer därför att undersöka vilken färgtemperatur som är lämpligast till olika badrumsaktiviteter. Tidigare studier tyder på att kalla färgtemperaturer från 4000 Kelvin (K) och uppåt är mera lämpliga som arbetsljus medan varma färgtemperaturer från 2700K till 4000K är mera lämpliga som avslappningsljus. Mer specifikt är studiens frågeställningar: ”Vilken färgtemperatur från 2700K till 6400K är lämpligast till sminkning/rakning?” och ”Vilken färgtemperatur från 2700K till 6400K är lämpligast till bad?” Studien genomfördes genom ett experiment med 25 stycken försökspersoner varav 15 stycken kvinnor och 10 stycken män och medelåldern var i åldersspannet 40–49år. Under experimentets gång fick försökspersonerna utvärdera belysningens inställning med fokus på färgtemperatur. Experimentet utfördes som två aktiviteter (sminkning/rakning och bad) och bestod av tre scenarios av färgtemperatur (2500K; 4000K; 6400K) som hade två olika ordningsföljder (dvs. 2700K/4000K/6400K och 6400K/2700K/4000K). Ordningsföljden bestämdes systematiskt i experimentet. Ett fjärde scenario i experimentet användes då försökspersonerna själva valde vilken färgtemperatur de föredrog utan att veta vilket exakt metriskt värde denna hade. Experimentet använde både kvalitativa och kvantitativa metoder som innefattade enkätfrågor i skalnivåer för de två aktiviteterna och de tre scenarios, samt en fråga med öppet svarsalternativ där försökspersonerna hade möjlighet att utveckla sina svar. Utifrån resultaten i denna studie rekommenderas en belysning där både färgte

This study was aimed to analyze the daily learning flow of early childhood inclusive education. The study used qualitative research, with a phenomenological approach in RA. An-Nahl, Jakarta. The data collection techniques used in this study were observation, interviews, focus group discussions, and documentation; then, they are analyzed descriptively with an interactive analysis model. The results obtained were the daily learning flow plan in the form of pre-opener, opener, energizer, activity, linking and summarizing, review, mission, closer applied by RA. The conclusion of this study was the modification of the daily learning flow, which is the flagship characteristic of RA., Este estudio tuvo como objetivo analizar el flujo de aprendizaje diario de la educación inclusiva en la primera infancia. El estudio utilizó investigación cualitativa, con un enfoque fenomenológico en la RA. An-Nahl, Yakarta. Las técnicas de recolección de datos utilizadas en este estudio fueron observación, entrevistas, discusiones de grupos focales y documentación; luego, se analizan descriptivamente con un modelo de análisis interactivo. Los resultados obtenidos fueron el plan de flujo de aprendizaje diario en forma de preaperturador, abridor, energizador, actividad, vinculación y resumen, revisión, misión, aplicación más cercana por RA. La conclusión de este estudio fue la modificación del flujo de aprendizaje diario, que es la característica principal de la RA.

U doktorskoj disertaciji evaluirani su interkorelacioni rezultati odnosa ključnih fizičko-hemijskih parametara i katjona metala u površinskoj vodi Dunava, Tise (na po tri selektovana reprezentativna lokaliteta) i kanala Dunav-Tisa-Dunav (na dva lokaliteta). U Kanalu Dunav-Tisa-Dunav praćene su i rezidualne katjonske koncentracije metala u sedimentu. Na osnovu podataka prisutnosti katjona metala u heterogenom sistemu tečno/čvrsto izračunate su po prvi put konstante podeonih procesa za ispitivane katjone metala. Primenom multivarijantnih statističkih metoda analizirani su korelacioni odnosi između ključnih fizičko-hemijskih parametara i koncentracionih nivoa rezidula katjona teških, lakih i semimetala. Faktorskom analizom (PCA) i klaster analizom sa dendogramima tumačeni, analizirani i diskutovani su dobijeni rezultati. Za optimalnog uočavanja korelacionih odnosa primenjeno je unapređeno rangiranje određenih skupova podataka (interkorelacije ključnih fizičko-hemijskih parametara i rezidua katjona metala) i grafički prikazanih Haseovih dijagrama primenom DART softvera (Decision Analysis by Ranking Techniques) za definisani model procene uticaja raspodele katjona toksičnih metala u heterogenom sistemu tečno/čvrsto na kvalitet površinskih voda., In the doctoral thesis are evaluated inter correlational results of key physicochemical parameters and metal cations in surface water of Danube, Tisa (on three selected representative sampling points) and canal Danube-Tisa-Danube (on two sampling sites). In the canal Danube-Tisa-Danube are also followed residual metal cations concentrations in sediment. Based on metal cations presence data in heterogeneous system liquid/solid for the first time partitioning processes constants are calculated for selected metal cations. Appling multivariate statistical methods correlations between key physicochemical parameters and concentration levels of residual heavy, light and semimetals cations are analysed. Using factorial analyse (PCA) and cluster analyse with dendograms obtained results were interpreted, analysed and discussed. For optimal comprehension of correlations, advanced method ranking of finite order sets is applied (inter correlations key physicochemical parameters and residual metal cations) and graphically shown Hasse diagrams obtained by DART software (Decision Analysis by Ranking Techniques) for defined impact assessment model of toxic metal cations partitioning in heterogeneous system liquid/solid for surface water quality.

Non-coding SNPs in the protein tyrosine phosphatase non-receptor type 2 (PTPN2) locus have been linked with several autoimmune diseases, including rheumatoid arthritis, type I diabetes, and inflammatory bowel disease. However, the functional consequences of these SNPs are poorly characterized. Herein, we show in blood cells that SNPs in the PTPN2 locus are highly correlated with DNA methylation levels at four CpG sites downstream of PTPN2 and expression levels of the long non-coding RNA (IncRNA) LINC01882 downstream of these CpG sites. We observed that LINC01882 is mainly expressed in T cells and that anti-CD3/CD28 activated naive CD4(+) T cells downregulate the expression of LINC01882. RNA sequencing analysis of LINC01882 knockdown in Jurkat T cells, using a combination of antisense oligo-nucleotides and RNA interference, revealed the upregulation of the transcription factor ZEB1 and kinase MAP2K4, both involved in IL-2 regulation. Overall, our data suggests the involvement of LINC01882 in T cell activation and hints towards an auxiliary role of these non-coding SNPs in autoimmunity associated with the PTPN2 locus.

[ES] El objetivo de este trabajo es el desarrollo de una aplicación móvil de realidad aumentada desarrollada bajo las nuevas librerías ARCore de Google. Estará enfocada en el ámbito de la salud y su finalidad será dar apoyo psicológico a lo largo de la terapia que atraviesa un paciente menor de edad con cáncer. La motivación para emprender el desarrollo de esta aplicación, parte de la idea de trabajar y aprender el funcionamiento de nuevas e innovadoras tecnologías. Actualmente el mercado de las aplicaciones de salud se encuentra en pleno auge y dentro de este sector existe una deficiencia de aplicaciones centradas en pacientes que deben aprender y comprender como conllevar una enfermedad grave como puede ser el cáncer. Este tipo de enfermedades pueden afectar gravemente a nivel psicológico al paciente, hasta el punto de no querer afrontarla y por tanto rendirse ante ella. La aplicación se ha desarrollado en su totalidad con Unity y en el lenguaje C#. Como resultado, se ha obtenido una aplicación de uso sencillo e intuitivo que interactúa con el usuario cuando reconoce un patrón relacionado con uno de los procedimientos aplicados al paciente a lo largo de la enfermedad, por ejemplo, un gotero, un plato de comida, una camilla, etc. Tras finalizar esta aplicación, se han asentado numerosas destrezas adquiridas a lo largo de la carrera y aprendido nuevas tecnologías como qué es la realidad aumentada, su funcionamiento y lo más importante, su gran utilidad en el ámbito de la salud y el gran apoyo que brinda tanto a pacientes como a profesionales médicos., [CA] L'objectiu d'este treball és el desenrotllament d'una aplicació mòbil de realitat augmentada desenrotllada davall les noves llibreries ARCore de Google. Estarà enfocada a l'àmbit de la salut i la seua finalitat serà donar suport psicològic al llarg de la teràpia que travessa un pacient menor d'edat amb càncer. La motivació per a emprendre el desenrotllament d'esta aplicació, part de la idea de treballar i aprendre el funcionament de noves i innovadores tecnologies. Actualment el mercat de les aplicacions de salut es troba en ple auge i dins d'este sector hi ha una deficiència d'aplicacions centrades en pacients que han d'aprendre i comprendre com comportar una malaltia greu com pot ser el càncer. Este tipus de malalties poden afectar greument nivell psicològic al pacient, fins al punt de no voler afrontar-la i per tant rendirse davant d'ella. L'aplicació s'ha desenrotllat en la seua totalitat amb Unity i en el llenguatge C#. Com resultat, s'ha obtingut una aplicació d'ús senzill i intuïtiu que interactua amb l'usuari quan reconeix un patró relacionat amb un dels procediments aplicats al pacient al llarg de la malaltia, per exemple, un goter, un plat de menjar, una llitera, etc. Després de finalitzar esta aplicació, s'han assentat nombroses destreses adquirides al llarg de la carrera i aprés noves tecnologies com què és la realitat augmentada, el seu funcionament i el més important, la seua gran utilitat en l'àmbit de la salut i el gran suport que brinda tant a pacients com a professionals metges., [EN] The objective of this work is the development of a mobile application which will incorporate augmented reality developed under the new ARCore libraries of the company Google. It will be focused on the field of health and its purpose will be to provide psychological support throughout the therapy that a sick patient goes through. The motivation to undertake the development of this application, part of the idea of working and learning the operation of new and innovative technologies. Currently the market of health applications are booming and within this sector there is a deficiency of applications focused on patients who must learn and understand how to lead a serious disease such as cancer. This type of illnesses can seriously affect the patient psychologically, to the point of not wanting to face it and therefore surrender to it. The application has been developed in its entirety with Unity and in the C # language. As a result, an application of simple and intuitive use has been obtained that interacts with the user when it recognizes a pattern related to one of the procedures applied to the patient throughout the illness, for example a dropper, a food plate, a stretcher, etc. After completing this application, they have settled numerous skills acquired throughout the career and learned new technologies such as what is augmented reality, its operation and most importantly, its great utility in the field of health and the great support it provides both to patients and to medical professionals.

Este proyecto añade un bloque de visualización objetiva al proyecto de telepresencia del Grupo de Imagen de la UPC que permite a una usuaria visualizar una escena remota, capturada con 3 cámaras RGBD, a través de unas gafas de realidad virtual (visualización subjetiva). El bloque desarrollado en este trabajo, añade una cámara RGBD en la sala donde se encuentra la usuaria de las gafas para aportar una visualización en tercera persona u objetiva de la interacción entre la usuaria y la sala remota. Se hace, pues, una transformación de la captura de la sala de visualización para conseguir un registro, rotación, escala y traslación, que reflejen correctamente la interacción., This project adds an objective visualization block to the telepresence project of the Image Group at UPC that lets a user visualize a remote scene, captured trough 3 RGBD cameras, with the help of a pair of virtual reality glasses (subjective visualization). The developed block in this report, adds a RGBD camera in the room where the user of the glasses is in order to provide a third person or objective view of the interaction between the user and the remote room. The capture of the visualization room is transformed to achieve a procedure for the registration, rotation, scale and translation, which correctly reflects the interaction., Aquest projecte afegeix un bloc de visualització objectiva al projecte de telepresència del Grup d'Imatge de la UPC que permet a una usuària visualitzar una escena remota, capturada amb 3 càmeres RGBD, a través d'unes ulleres de realitat virtual (visualització subjectiva). El bloc desenvolupat en aquest treball, afegeix una càmera RGBD a la sala on es troba la usuària de les ulleres per aportar una visualització en tercera persona o objectiva de la interacció entre la usuària i la sala remota. Es fa, doncs, una transformació de la captura de la sala de visualització per aconseguir un registre, rotació, escala i translació, que reflecteixin correctament la interacció.

Aquest projecte es basa en l'elaboració i utilització d'aplicacions de realitat augmentada de manera transversal en els diferents nivells de l'educació secundària, també implicaria diferents àmbits però principalment orientat al tecnològic. L'objectiu és treure-li el major rendiment a les TIC i reduir la taxa d'alumnes de baix rendiment. Una proposta en què els alumnes dels primers cursos dissenyin objectes 3d amb un programa senzill, els de 3r i 4t confeccionin l'aplicació, per poder visualitzar-los en 3d i R.A. Tots els programes plantejats per a aquest projecte són lliures. Aquesta aplicació també l'aprofitarien en l'àmbit artístic, per visualitzar millor una figura i dibuixar-la en diferents vistes, o en el científic per a la visualització de diversos elements. En l'aspecte psico-pedagògic propicia el constructivisme, fent que l'alumne construeixi els seus propis objectes, li ajuda a visualitzar formes abstractes i també aquesta dinàmica pot ser útil per motivar l'alumnat així com per experimentar amb les noves tecnologies i no només actuar com a usuaris.

Chronic inflammatory autoimmune diseases leading to target tissue destruction and disability are not only causing increase in patients' suffering but also contribute to huge economic burden for the society. General increase in life expectancy and high prevalence of these diseases both in elderly and younger population emphasize the importance of developing safe and effective vaccines. In this review, at first the possible mechanisms and risk factors associated with chronic inflammatory autoimmune diseases, such as rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE) and type 1 diabetes (T1D) are discussed. Current advances in the development of vaccines for such autoimmune diseases, particularly those based on DNA, altered peptide ligands and peptide loaded MHC II complexes are discussed in detail. Finally, strategies for improving the efficacy of potential vaccines are explored. © 2018 Elsevier Ltd, Funding text: KSN would like to thank Southern Medical University, Guangzhou, PR China for startup grant (C1034211). We acknowledge team grant from Guangdong province (201001Y04675344) and matching grant from Dongguan city, PR China.

Objectives: RANK ligand (RANKL) is involved in destruction and osteoporosis in RA. In this study, the relationships between RANKL and ACPA, anti-carbamylated protein antibodies (anti-CarP), cytokines and chemokines were analysed in individuals before the onset of RA symptoms, and their associations with radiological findings at disease onset were assessed. Methods: This was a case-control study performed within the Medical Biobank of Northern Sweden that included 470 pre-symptomatic individuals [334 women and 136 men; mean (S.D.) age 52.3 (9.4) years] using blood samples donated before symptom onset (pre-dating time; 5.0 years) and 96 controls (60 women and 36 men). Plasma was analysed for RANKL (BioVendor, Karasek, Brno, Czech Republic), anti-CCP2 antibodies (Eurodiagnostics, Malmo, Sweden), anti-CarP antibodies (in-house ELISA), ACPA specificities (ISAC-platform, Phadia AB, Uppsala, Sweden) and cytokines/chemokines (Meso Scale Discovery methods, Rockville, MD, USA). Radiographs of hands and feet were graded using the Larsen score. Results: The concentration of RANKL was higher in the pre-symptomatic individuals compared with controls; mean (S.E.M.): 0.50 (0.03) vs 0.22 (0.02) nmol/l (P < 0.001). The concentration increased gradually over time until symptom onset but appeared later than ACPA/RF/anti-CarP antibodies. Positivity for these antibodies yielded higher levels of RANKL compared with seronegativity (P < 0.001). RANKL concentrations were significantly associated with IL-6 and IL-10 concentrations. The combination of positivity for RANKL and anti-CarP antibodies resulted in a higher Larsen score at diagnosis beta = 6.18 (95% CI: 0.93, 11.43; P = 0.022). Conclusion: RANKL concentrations were increased several years before symptom onset for RA, particularly in ACPA/RF/anti-CarP-positive individuals, all detectable earlier than RANKL. Positivity for RANKL and anti-CarP antibodies yielded the highest Larsen score at disease onset.