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The optimal treatment for patients with asymptomatic carotid artery stenosis is under debate. Since best medical treatment (BMT) has improved over time, the benefit of carotid endarterectomy (CEA) or carotid artery stenting (CAS) is unclear. Randomised data comparing the effect of CEA and CAS versus BMT alone are absent. We aimed to directly compare CEA plus BMT with CAS plus BMT and both with BMT only.SPACE-2 was a multicentre, randomised, controlled trial at 36 study centres in Austria, Germany, and Switzerland. We enrolled participants aged 50-85 years with asymptomatic carotid artery stenosis at the distal common carotid artery or the extracranial internal carotid artery of at least 70%, according to European Carotid Surgery Trial criteria. Initially designed as a three-arm trial including one group for BMT alone (with a randomised allocation ratio of 2·9:2·9:1), the SPACE-2 study design was amended (due to slow recruitment) to become two substudies with two arms each comparing CEA plus BMT with BMT alone (SPACE-2a) and CAS plus BMT with BMT alone (SPACE-2b); in each case in a 1:1 randomisation. Participants and clinicians were not masked to allocation. The primary efficacy endpoint was the cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years. The primary safety endpoint was any stroke or death from any cause within 30 days after CEA or CAS. The primary analysis was by intention-to treat, which included all randomly assigned patients in SPACE-2, SPACE-2a, and SPACE-2b, analysed using meta-analysis of individual patient data. We did two-step hierarchical testing to first show superiority of CEA and CAS to BMT alone then to assess non-inferiority of CAS to CEA. Originally, we planned to recruit 3640 patients; however, the study had to be stopped prematurely due to insufficient recruitment. This report presents the primary analysis at 5-year follow-up. This trial is registered with ISRCTN, number ISRCTN78592017.513 patients across SPACE-2, SPACE-2a, and SPACE-2b were recruited and surveyed between July 9, 2009, and Dec 12, 2019, of whom 203 (40%) were allocated to CEA plus BMT, 197 (38%) to CAS plus BMT, and 113 (22%) to BMT alone. Median follow-up was 59·9 months (IQR 46·6-60·0). The cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years (primary efficacy endpoint) was 2·5% (95% CI 1·0-5·8) with CEA plus BMT, 4·4% (2·2-8·6) with CAS plus BMT, and 3·1% (1·0-9·4) with BMT alone. Cox proportional-hazard testing showed no difference in risk for the primary efficacy endpoint for CEA plus BMT versus BMT alone (hazard ratio [HR] 0·93, 95% CI 0·22-3·91; p=0·93) or for CAS plus BMT versus BMT alone (1·55, 0·41-5·85; p=0·52). Superiority of CEA or CAS to BMT was not shown, therefore non-inferiority testing was not done. In both the CEA group and the CAS group, five strokes and no deaths occurred in the 30-day period after the procedure. During the 5-year follow-up period, three ipsilateral strokes occurred in both the CAS plus BMT and BMT alone group, with none in the CEA plus BMT group.CEA plus BMT or CAS plus BMT were not found to be superior to BMT alone regarding risk of any stroke or death within 30 days or ipsilateral stroke during the 5-year observation period. Because of the small sample size, results should be interpreted with caution.German Federal Ministry of Education and Research (BMBF) and German Research Foundation (DFG).

Organic farming is a promising but still debated option to ensure sustainable agriculture. However, whether organic farming fosters synergies or mitigates tradeoffs between biodiversity, ecosystem services and crop production has rarely been quantified. Here, we investigate relationships between multitrophic diversity (14 taxa above and belowground), yield, natural pest control and soil quality (14 proxies of ecosystem services) in organic and conventional vineyards along a landscape gradient. Organic farming enhanced biodiversity and pest control, but decreased wine production. Compared to conventional systems, multitrophic diversity was 15 % higher, and pest control services were 9 % higher in organic systems, while wine production was 11 % lower. Regardless of management type, we found a strong tradeoff between wine production and pest control, but not between wine production and biodiversity. The landscape context was not a strong moderator of organic farming effects across taxa groups and ecosystem services, but affected specific taxa and ecosystem services, especially natural pest control. Our study reveals that wine production and biodiversity conservation do not necessarily exclude each other, which implies the existence of a safe operating space where biodiversity and wine production can be combined. We conclude that organic farming can contribute to improve the sustainability of viticulture, but needs to be complemented by management options at the local and landscape scales in order to fully balance biodiversity conservation with the simultaneous provision of multiple ecosystem services., This research was funded by the research project SECBIVIT, which was funded through the 2017–2018 Belmont Forum and BiodivERsA joint call for research proposals, under the BiodivScen ERA-Net COFUND program, with the funding organizations: Agencia Estatal de Investigación (Ministerio de Ciencia e Innovación/Spain, grant PCI2018-092938; MCIN/AEI/10.13039/501100011033); Austrian Science Fund (FWF) (grant number I 4025-B32); Federal Ministry of Education and Research (BMBF/Germany) (grant number 031A349I); French National Research Agency (ANR); Netherlands Organization for Scientific Research (NWO); National Science Foundation (grant #1850943); and Romanian Executive Agency for Higher Education, Research, Development, and Innovation Funding (UEFISCDI). The authors also acknowledge the support of the ECOPHYTO 2+ Plan under the grant X4IN33VI (OPERA project) as well as the support the French National Research Agency (ANR) under the grant 20-PCPA-0010 (PPR Vitae, Cultivating the grapevine without pesticides: towards agroecological wine-producing socio-ecosystems). We thank Evelyne Thys and Hugo Hernandez for their help in field sampling, Lionel Delbac for the Lobesia botrana rearing, Alexis Saintilan for identifying pollinators, and Edith Gruber for identifying earthworms.

Summary The introduction of disease-modifying anti-rheumatic drug therapies for treating children and adolescents with chronic arthritis (ie, juvenile idiopathic arthritis [JIA]) has revolutionised care and outcomes. The biologic revolution continues to expand, with ever-changing immunological targets coming to market after basic research and clinical trials. The first class of biologics that was beneficial for children with JIA was tumour necrosis factor (TNF) inhibitors. If used early and aggressively, TNF inhibitors are capable of inducing disease remission for most of the seven subtypes of JIA, with the exception of systemic JIA (which more frequently responds to interleukin [IL]-1 or IL-6 inhibition). Nevertheless, there are still subsets of patients with JIA with disease that is difficult to treat or who develop extra-articular features that require a different therapeutic approach. Although finding an effective biological therapy for individual children with JIA can be trial and error, ongoing research and clinical trials are providing insight into a more personalised approach to care. In addition, redefining the JIA classification, in part based on shared similarities with various adult arthritides, could allow for extrapolation of knowledge from studies in adults with chronic arthritis.

Future automated vehicles may be equipped with external Human-Machine Interfaces (eHMIs). Currently, little is known about the effect of the perspective of the eHMI message on crossing decisions of pedestrians. We performed an experiment to examine the effects of images depicting eHMI messages of different perspectives (egocentric from the pedestrian’s point of view: WALK, DON’T WALK, allocentric: BRAKING, DRIVING, and ambiguous: GO, STOP) on participants’ (N = 103) crossing decisions, response times, and eye movements. Considering that crossing the road can be cognitively demanding, we added a memory task in two-thirds of the trials. The results showed that egocentric messages yielded higher subjective clarity ratings than the other messages as well as higher objective clarity scores (i.e., more uniform crossing decisions) and faster response times than the allocentric BRAKING and the ambiguous STOP. When participants were subjected to the memory task, pupil diameter increased, and crossing decisions were reached faster as compared to trials without memory task. Regarding the ambiguous messages, most participants crossed for the GO message and did not cross for the STOP message, which points towards an egocentric perspective taken by the participant. More lengthy text messages (e.g., DON’T WALK) yielded a higher number of saccades but did not cause slower response times. We conclude that pedestrians find egocentric eHMI messages clearer than allocentric ones, and take an egocentric perspective if the message is ambiguous. Our results may have important implications, as the consensus among eHMI researchers appears to be that egocentric text-based eHMIs should not be used in traffic.

Sustainable land use in agricultural landscapes is essential to counteract the global decline of biodiversity, as well to ensure ecosystem services like natural pest control. Phytoseiid mites are key natural enemies of pest mites in vineyards but how local management and landscape context affect phytoseiid mites remains poorly known. In this study, we examined the effects of farming systems, inter-row management and landscape composition on phytoseiid mite communities in 156 vineyards across five European wine-growing regions. Our results showed that phytoseiid communities were mainly dominated by one or two phytoseiid species across Europe and that local management was a major factor affecting population densities. According to the wine-growing regions, phytoseiid mite densities benefited from integrated pest management or conventional farming compared to organic farming and from spontaneous vegetation cover compared to seeded cover crops. Moreover, mite densities benefited from increasing proportions of vineyards at the landscape scale. The farming systems effects were most likely related to the positive impact of the lower pesticide use in integrated and conventional vineyards. The positive effect of spontaneous vegetation cover could be related to a better supply of nutritive pollen as food resource compared to seeded cover crops, which depends on the plant species in the inter-row. Our findings indicated accordingly that a reduced pesticide use, and inter-row management are crucial factors for promoting pest control by predatory mites in European vineyards. Moreover, the proportion of viticultural area in the landscape is a considerable factor to retain stable phytoseiid mite populations., This research was funded by the research project SECBIVIT, which was funded through the 2017-2018 Belmont Forum and BiodivERsA joint call for research proposals, under the BiodivScen ERA-Net COFUND program, with the funding organizations: Agencia Estatal de Investigación (Ministerio de ciencia e innovación/ES/Grant #10.13039/501100011033), Austrian Science Fund (AT/Grant #I 4025-B32), Federal Ministry of Education and Research and Projektträger VDI/VDE Innovation + Technik GmbH (DE), French National Research Agency (FR), Netherlands Organisation for Scientific Research (NL), National Science Foundation (US/Grant #1850943) and Romanian Executive Agency for Higher Education, Research, Development and Innovation Funding (RO).

Additive manufacturing is becoming increasingly important for industrial applications. Especially laser powder bed fusion processes play a decisive role. However, the technology often lacks in reliability and part quality due to complex process interactions and disturbing influences. To counteract these limitations, a flexible and high-dynamic control of relevant process parameters, taking into account the transient process conditions, is indispensable. Currently, the most process parameters are often kept constant, since the used control systems do not offer real-time capable interfaces for intervention. To enable the adjustment of parameters during the process, an open control architecture for galvanometer scanners and laser sources was developed. The architecture is based on an industrial control system in combination with a field-programmable gate array (FPGA) communicating via a real-time fieldbus. The novel control architecture is used to integrate a model-based feedforward control, adjusting the laser power, scan speed and scan strategy based on the current powder bed temperature calculated by a two-dimensional thermal model during run time. An integrated learning algorithm autonomously tunes the process parameters during the manufacturing process and determines the optimal combination of laser power, scan speed and powder bed temperature to achieve a homogeneous melt pool. On average, the standard deviation of the powder bed temperature along the scan path was reduced by 48% for the simulated test cases.

Noninfectious inflammatory eye diseases (NIIEDs), such as uveitis, is a general term used to describe a complex mix of acute, chronic, allergic, and inflammatory disorders. Prior literature has established that, in addition to severe clinical burden, NIIEDs is associated with significant economic burden for US payers; however, no literature provides a current estimate of the economic burden associated with patients with high-cost NIIEDs. This study aimed to better understand the cost and resource use distribution and predictors of patients with high-cost NIIEDs.This retrospective cohort study selected adult patients with NIIEDs from a large US administrative claims database between 2006 and 2015. Among the included patients, total all-cause health care costs were calculated for a randomly selected 12-month period. Patients in the top 20% of total all-cause health care costs were identified as high-cost patients; the remaining patients were identified as lower-cost patients. Patient demographic characteristics, clinical characteristics, cost, and health care resource utilization (HRU) were compared. Logistic regression models were used to determine characteristics associated with high-cost patients.Patients with NIIEDs (n = 14,879) were categorized into 2976 high-cost and 11,903 lower-cost patients. High-cost patients with NIIEDs were significantly more likely to experience blindness, cataract, cystoid macular degeneration, retinal detachment, and visual disturbances during the follow-up period than the lower-cost patients (all P 0.05). The high-cost patients accounted for ~77% of the total all-cause health care spend. High-cost patients incurred an average annual total health care cost of $59,873, and the top 1 percentile incurred $349,967 during the follow-up period. Hospitalization was a key cost driver among the high-cost patients, accounting for 50% of the total cost among the top 1 percentile of patients. High-cost patients were more likely to have specific autoimmune diseases, inpatient admission, and use of biologic and immunosuppressant agents.A small segment of patients with NIIEDs consumed most resources. This study identified several predictors based on patient characteristics and HRU that may help inform the profile of patients with NIIEDs with the highest health care needs. As such, patients with a given profile can be selected for targeted interventions by clinicians to potentially help improve quality of care and to reduce costs.

Objective: To translate and validate the Brazilian Portuguese version of the Transition Readiness Assessment Questionnaire in a population of adolescents and young adults with chronic rheumatologic disorders. This questionnaire evaluates the patient's readiness for making the transition from the pediatric health service to adult care. Methods: The four‐phase methodology for the translation and validation of generic questionnaires was followed, including translation, back‐translation, pilot testing and clinical validation of the final tool. The confirmatory factor analysis was used for clinical validation and the Cronbach's alpha coefficient was used to assess the overall internal consistency of the final tool. Results: A total of 150 patients with a mean age of 17.0 years (SD = 2.2 years, range 14–21 years) were enrolled for the final tool validation. Of those, 71 patients had juvenile systemic lupus erythematosus (47.3%), 64 had juvenile idiopathic arthritis (42.7%), and 15 had juvenile dermatomyositis (10%). During the confirmatory factor analysis, the dimension “Talking with providers” consisting of two questions, was considered as not fitting the translated questionnaire due to a very high ceiling effect and was therefore excluded. All other translated items favorably contributed to the overall consistency of the final tool; removing that dimension did not result in a substantial increase in Cronbach's alpha, which was 0.776. Conclusions: The Brazilian Portuguese version of the Transition Readiness Assessment Questionnaire was validated in a population of transitional patients with chronic rheumatologic disorders, after one dimension from the original questionnaire was excluded. It is a non‐specific disease questionnaire; thus, it can be used to evaluate the transition readiness of Brazilian patients with other chronic diseases. Resumo: Objetivo: Traduzir para o português brasileiro e validar o Questionário de Avaliação do Preparo para a Transição em uma população de adolescentes e adultos jovens com doenças reumáticas crônicas. Este questionário avalia o preparo do paciente para realizar a transição do serviço de saúde pediátrico para a assistência ao adulto. Métodos: Seguimos a metodologia de quatro etapas para a tradução e validação de questionários genéricos que inclui tradução, retrotradução, teste piloto e validação clínica do instrumento final. Utilizamos Análise Fatorial Confirmatória e Coeficiente Alfa de Cronbach para testar a validade do instrumento e sua consistência interna. Resultados: Responderam ao questionário traduzido e adaptado 150 pacientes. A média de idade foi de 17,0 anos (DP = 2,2 anos, variação 14‐21 anos). Tinham o diagnóstico de lúpus eritematoso sistêmico juvenil 71 pacientes (47,3%), 64 (42,7%) artrite idiopática juvenil e 15 (10%) dermatomiosite juvenil. Durante a análise fatorial confirmatória, a dimensão “Falando com a Equipe Médica” contendo duas questões teve que ser removida devido à presença de expressivo efeito teto. Todas as outras questões restantes contribuíram favoravelmente para aumentar a consistência interna do questionário, obteve‐se um Coeficiente Alfa de Cronbach de 0,776. Conclusões: O Questionário de Avaliação do Preparo para a Transição na sua versão em português brasileiro pode ser validado em uma população de pacientes com doenças reumáticas crônicas em transição, com a exclusão de uma dimensão do questionário original. Por ser um questionário não específico para doenças reumáticas, poderá ser utilizado para avaliar o preparo para a transição de outros pacientes brasileiros com doenças crônicas. Keywords: Transition readiness tool, TRAQ, Brazil, Rheumatology, Adolescent health services, Research in health services, Palavras‐chave: Avaliação do preparo para a transição, TRAQ, Brasil, Reumatologia, Serviços de saúde do adolescente, Pesquisa em serviços de saúde

Type 2 diabetes is associated with increased mortality. There is some data that sulphonylurea therapy may contribute to this.To compare all-cause 3-year mortality of patients on sulphonylurea monotherapy to that of patients on metformin monotherapy after adjusting for potential confounders.We searched the Maltese national electronic database for diabetes treatment in April 2014. This is an electronic database of all treatment that patients are prescribed through the local National Health Service. We identified patients on metformin or sulphonylurea monotherapy and linked this to the national mortality database and the laboratory information system.There were 25,792 persons who were on treatment for diabetes in April 2014. Of these, 9977 were on metformin monotherapy and 1717 on sulphonylurea monotherapy. This cohort was followed up until April 2017. There were 2518 deaths (9.76%) during this period, giving an average of 32.5 deaths per 1000 persons with diabetes. Logistic regression showed that persons on sulphonylurea monotherapy were 2.03 (95% CI 1.68-2.44, p .001) times more likely to die within 3 years than persons on metformin monotherapy, after adjusting for age, eGFR and HbA1c. The logistic regression model was statistically significant, p .001. Additional adjustment for LDL-cholesterol, HDL-cholesterol and urinary albumin-creatinine ratio did not alter the results.Our data shows that sulphonylurea monotherapy is associated with higher all-cause mortality when compared to metformin monotherapy after adjusting for potential confounders.