Peroxide-based crosslinking of solid silicone rubber, part II: The counter-intuitive influence of dicumylperoxide concentration on crosslink effectiveness and related network structure

Application of elastomers in general demands the conversion of their soluble networks into crosslinked structures. This abrupt change causes several modifications, both in the atomic/molecular level and at the macro-scale. In this study, solid silicone rubber (high molecular weight poly(dimethylsiloxane)), was crosslinked with dicumylperoxide (DCP), a widely used crosslinking agent by the rubber industry. The changes caused by different DCP concentrations were investigated, aiming to bring attention to the molecular transformations, usually neglected when processing-oriented studies are conducted. DCP concentration showed a limited contribution to the network's molecular dynamics, which was found to be mainly dominated by entanglements. The dominance of entanglements over other molecular constraints, like crosslink points, justifies the threshold and counter-intuitive behavior of tensile and hardness properties. However, differences were found in the crystallization ability after crosslinking, when the more crosslink points were introduced, the lower the crystallinity was and the less stable the PDMS crystallites were. In addition to providing a deeper understanding of an industrially applied rubber system n terms of the effective concentration of DCP, and the reasoning behind such concentration, the findings of this study add to the state-of-the-art comprehension of elastomeric networks, and how they behave on a molecular level

A core set of risk factors in individuals at risk of rheumatoid arthritis: a systematic literature review informing the EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis

Background There is significant interest in determining risk factors in individuals at risk of rheumatoid arthritis (RA). A core set of risk factors for clinical arthritis development has not been defined. Methods A literature search and systematic literature review (SLR) was conducted to identify risk factors in individuals at risk of RA using Medline, Embase, PubMed and Central databases. Results 3854 articles were identified by the literature search. After screening of titles, 138 abstracts were reviewed and 96 articles finally included. Fifty-three articles included data on risk factors including autoantibodies, subclinical inflammation on imaging, clinical features, serum and cellular biomarkers and genetic markers. Risk factors were dependent on the at-risk population. There was good evidence for serum anticitrullinated protein antibodies (ACPA) levels, as risk factors for arthritis in all at-risk populations (n=13 articles). Subclinical inflammation on ultrasound (n=12) and MRI (n=6) was reported as a risk factor in multiple studies in at-risk individuals with musculoskeletal (MSK) symptoms and undifferentiated arthritis (UA). Clinical features were reported as a risk factor in at-risk individuals with MSK symptoms and UA (n=13). Other risk factors, including serum and cellular markers were less frequently reported. Conclusions Risk factors for arthritis development in RA are specific to the at-risk population. Serum ACPA confers risk in all populations; subclinical inflammation on imaging and clinical features confer risk in at-risk individuals with MSK symptoms. This SLR informed the EULAR taskforce for points to consider on conducting clinical trials and studies in individuals at risk of RA

BAERLIN2014 -The influence of land surface types on and the horizontal heterogeneity of air pollutant levels in Berlin

Urban air quality and human health are among the key aspects of future urban planning. In order to address pollutants such as ozone and particulate matter, efforts need to be made to quantify and reduce their concentrations. One important aspect in understanding urban air quality is the influence of urban vegetation which may act as both emitter and sink for trace gases and aerosol particles. In this context, the "Berlin Air quality and Ecosystem Research: Local and long-range Impact of anthropogenic and Natural hydrocarbons 2014" (BAERLIN2014) campaign was conducted between 2 June and 29 August in the metropolitan area of Berlin and Brandenburg, Germany. The predominant goals of the campaign were (1) the characterization of urban gaseous and particulate pollution and its attribution to anthropogenic and natural sources in the region of interest, especially considering the connection between biogenic volatile organic compounds and particulates and ozone; (2) the quantification of the impact of urban vegetation on organic trace gas levels and the presence of oxidants such as ozone; and (3) to explain the local heterogeneity of pollutants by defining the distribution of sources and sinks relevant for the interpretation of model simulations. In order to do so, the campaign included stationary measurements at urban background station and mobile observations carried out from bicycle, van and airborne platforms. This paper provides an overview of the mobile measurements (Mobile BAERLIN2014) and general conclusions drawn from the analysis. Bicycle measurements showed micro-scale variations of temperature and particulate matter, displaying a substantial reduction of mean temperatures and particulate levels in the proximity of vegetated areas compared to typical urban residential area (background) measurements. Van measurements extended the area covered by bicycle observations and included continuous measurements of O3, NOx, CO, CO2 and point-wise measurement of volatile organic compounds (VOCs) at representative sites for traffic- and vegetation-affected sites. The quantification displayed notable horizontal heterogeneity of the short-lived gases and particle number concentrations. For example, baseline concentrations of the traffic-related chemical species CO and NO varied on average by up to ±22.2 and ±63.5 %, respectively, on the scale of 100 m around any measurement location. Airborne observations revealed the dominant source of elevated urban particulate number and mass concentrations being local, i.e., not being caused by long-range transport. Surface-based observations related these two parameters predominantly to traffic sources. Vegetated areas lowered the pollutant concentrations substantially with ozone being reduced most by coniferous forests, which is most likely caused by their reactive biogenic VOC emissions. With respect to the overall potential to reduce air pollutant levels, forests were found to result in the largest decrease, followed by parks and facilities for sports and leisure. Surface temperature was generally 0.6–2.1 °C lower in vegetated regions, which in turn will have an impact on tropospheric chemical processes. Based on our findings, effective future mitigation activities to provide a more sustainable and healthier urban environment should focus predominantly on reducing fossil-fuel emissions from traffic as well as on increasing vegetated areas

Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors : a systematic literature research

Objectives: Review of efficacy and safety of Janus kinase (JAK) inhibition in immune-mediated inflammatory diseases (IMIDs). Methods: A systematic literature research (SLR) of all publications on JAK inhibitors (JAKi) treatment published until March 2019 using MEDLINE, EMBASE and the Cochrane Library. Efficacy and safety were assessed in randomised controlled trials (RCTs), integrating long-term extension periods additionally for safety evaluation. Results: 3454 abstracts were screened with 85 included in the final analysis (efficacy and RCT safety: n=72; safety only: n=13). Efficacy of RCTs investigating tofacitinib (TOFA, n=27), baricitinib (BARI, n=9), upadacitinib (UPA, n=14), filgotinib (FILGO, n=7), decernotinib (DEC, n=3) and peficitinib (PEF, n=7) was evaluated. Six head-to-head trials comparing JAKi with tumour necrosis factor inhibitors (TNFi) were included. Efficacy of JAKi was shown in rheumatoid arthritis (RA) for all agents, psoriatic arthritis (TOFA, FILGO), ankylosing spondylitis (TOFA, FILGO), systemic lupus erythematosus (BARI), chronic plaque psoriasis (TOFA, BARI, PEF), ulcerative colitis (TOFA, UPA), Crohn’s disease (UPA, FILGO) and atopic dermatitis (TOFA, BARI, UPA). Safety analysis of 72 RCTs, one cohort study and 12 articles on long-term extension studies showed increased risks for infections, especially herpes zoster, serious infections and numerically higher rates of venous thromboembolic events. No increased malignancy rates or major adverse cardiac events were observed. Conclusion: JAKi provide good efficacy compared to placebo (and to TNFi in RA and Pso) across various IMIDs with an acceptable safety profile. This SLR informed the task force on points to consider for the treatment of IMIDs with JAKi with the available evidence

Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a consensus statement

Objectives: Janus kinase inhibitors (JAKi) have been approved for use in various immune-mediated inflammatory diseases. With five agents licensed, it was timely to summarise the current understanding of JAKi use based on a systematic literature review (SLR) on efficacy and safety. Methods: Existing data were evaluated by a steering committee and subsequently reviewed by a 29 person expert committee leading to the formulation of a consensus statement that may assist the clinicians, patients and other stakeholders once the decision is made to commence a JAKi. The committee included patients, rheumatologists, a gastroenterologist, a haematologist, a dermatologist, an infectious disease specialist and a health professional. The SLR informed the Task Force on controlled and open clinical trials, registry data, phase 4 trials and meta-analyses. In addition, approval of new compounds by, and warnings from regulators that were issued after the end of the SLR search date were taken into consideration. Results: The Task Force agreed on and developed four general principles and a total of 26 points for consideration which were grouped into six areas addressing indications, treatment dose and comedication, contraindications, pretreatment screening and risks, laboratory and clinical follow-up examinations, and adverse events. Levels of evidence and strengths of recommendations were determined based on the SLR and levels of agreement were voted on for every point, reaching a range between 8.8 and 9.9 on a 10-point scale. Conclusion: The consensus provides an assessment of evidence for efficacy and safety of an important therapeutic class with guidance on issues of practical management

EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis

Background Despite growing interest, there is no guidance or consensus on how to conduct clinical trials and observational studies in populations at risk of rheumatoid arthritis (RA). Methods An European League Against Rheumatism (EULAR) task force formulated four research questions to be addressed by systematic literature review (SLR). The SLR results informed consensus statements. One overarching principle, 10 points to consider (PTC) and a research agenda were proposed. Task force members rated their level of agreement (1–10) for each PTC. Results Epidemiological and demographic characteristics should be measured in all clinical trials and studies in at-risk individuals. Different at-risk populations, identified according to clinical presentation, were defined: asymptomatic, musculoskeletal symptoms without arthritis and early clinical arthritis. Study end-points should include the development of subclinical inflammation on imaging, clinical arthritis, RA and subsequent achievement of arthritis remission. Risk factors should be assessed at baseline and re-evaluated where appropriate; they include genetic markers and autoantibody profiling and additionally clinical symptoms and subclinical inflammation on imaging in those with symptoms and/or clinical arthritis. Trials should address the effect of the intervention on risk factors, as well as progression to clinical arthritis or RA. In patients with early clinical arthritis, pharmacological intervention has the potential to prevent RA development. Participants’ knowledge of their RA risk may inform their decision to participate; information should be provided using an individually tailored approach. Conclusion These consensus statements provide data-driven guidance for rheumatologists, health professionals and investigators conducting clinical trials and observational studies in individuals at risk of RA

BAERLIN2014-stationary measurements and source apportionment at an urban background station in Berlin, Germany

The "Berlin Air quality and Ecosystem Research: Local and long-range Impact of anthropogenic and Natural hydrocarbons" (BAERLIN2014) campaign was conducted during the 3 summer months (June-August) of 2014. During this measurement campaign, both stationary and mobile measurements were undertaken to address complementary aims. This paper provides an overview of the stationary measurements and results that were focused on characterization of gaseous and particulate pollution, including source attribution, in the Berlin-Potsdam area, and quantification of the role of natural sources in determining levels of ozone and related gaseous pollutants. Results show that biogenic contributions to ozone and particulate matter are substantial. One indicator for ozone formation, the OH reactivity, showed a 31% (0.82 +/- 0.44 s(-1) and 75% (3.7 +/- 0.90 s(-1) contribution from biogenic non-methane volatile organic com-pounds (NMVOCs) for urban background (2.6 +/- 0.68 s(-1) and urban park (4.9 +/- 1.0 s(-1) location, respectively, emphasizing the importance of such locations as sources of biogenic NMVOCs in urban areas. A comparison to NMVOC measurements made in Berlin approximately 20 years earlier generally show lower levels today for anthropogenic NMVOCs. A substantial contribution of secondary organic and inorganic aerosol to PM10 concentrations was quantified. In addition to secondary aerosols, source apportionment analysis of the organic carbon fraction identified the contribution of biogenic (plant-based) particulate matter, as well as primary contributions from vehicles, with a larger contribution from diesel compared to gasoline vehicles, as well as a relatively small contribution from wood burning, linked to measured levoglucosan

Development and external validation of a clinical prediction model for functional impairment after intracranial tumor surgery

OBJECTIVE Decision-making for intracranial tumor surgery requires balancing the oncological benefit against the risk for resection-related impairment. Risk estimates are commonly based on subjective experience and generalized num-bers from the literature, but even experienced surgeons overestimate functional outcome after surgery. Today, there is no reliable and objective way to preoperatively predict an individual patient's risk of experiencing any functional impair-ment. METHODS The authors developed a prediction model for functional impairment at 3 to 6 months after microsurgical resection, defined as a decrease in Karnofsky Performance Status of >= 10 points. Two prospective registries in Swit- zerland and Italy were used for development. External validation was performed in 7 cohorts from Sweden, Norway, Germany, Austria, and the Netherlands. Age, sex, prior surgery, tumor histology and maximum diameter, expected major brain vessel or cranial nerve manipulation, resection in eloquent areas and the posterior fossa, and surgical approach were recorded. Discrimination and calibration metrics were evaluated. RESULTS In the development (2437 patients, 48.2% male; mean age +/- SD: 55 +/- 15 years) and external validation (2427 patients, 42.4% male; mean age +/- SD: 58 +/- 13 years) cohorts, functional impairment rates were 21.5% and 28.5%, respectively. In the development cohort, area under the curve (AUC) values of 0.72 (95% CI 0.69-0.74) were observed. In the pooled external validation cohort, the AUC was 0.72 (95% CI 0.69-0.74), confirming generalizability. Calibration plots indicated fair calibration in both cohorts. The tool has been incorporated into a web-based application available at https://neurosurgery.shinyapps.io/impairment/. CONCLUSIONS Functional impairment after intracranial tumor surgery remains extraordinarily difficult to predict, al- though machine learning can help quantify risk. This externally validated prediction tool can serve as the basis for case by-case discussions and risk-to-benefit estimation of surgical treatment in the individual patient.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update

Background: Targeting interleukin (IL)-6 has become a major therapeutic strategy in the treatment of immune-mediated inflammatory disease. Interference with the IL-6 pathway can be directed at the specific receptor using anti-IL-6Rα antibodies or by directly inhibiting the IL-6 cytokine. This paper is an update of a previous consensus document, based on most recent evidence and expert opinion, that aims to inform on the medical use of interfering with the IL-6 pathway. Methods: A systematic literature research was performed that focused on IL-6-pathway inhibitors in inflammatory diseases. Evidence was put in context by a large group of international experts and patients in a subsequent consensus process. All were involved in formulating the consensus statements, and in the preparation of this document. Results: The consensus process covered relevant aspects of dosing and populations for different indications of IL-6 pathway inhibitors that are approved across the world, including rheumatoid arthritis, polyarticular-course and systemic juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still’s disease, Castleman’s disease, chimeric antigen receptor-T-cell-induced cytokine release syndrome, neuromyelitis optica spectrum disorder and severe COVID-19. Also addressed were other clinical aspects of the use of IL-6 pathway inhibitors, including pretreatment screening, safety, contraindications and monitoring. Conclusions: The document provides a comprehensive consensus on the use of IL-6 inhibition to treat inflammatory disorders to inform healthcare professionals (including researchers), patients, administrators and payers