Direct laser-written optomechanical membranes in fiber Fabry-Perot cavities

Integrated micro and nanophotonic optomechanical experiments enable the manipulation of mechanical resonators on the single phonon level. Interfacing these structures requires elaborate techniques limited in tunability, flexibility, and scaling towards multi-mode systems. Here, we demonstrate a cavity optomechanical experiment using 3D-laser-written polymer membranes inside fiber Fabry-Perot cavities. Vacuum coupling strengths of ~ 30 kHz to the fundamental megahertz mechanical mode are reached. We observe optomechanical spring tuning of the mechanical resonator by tens of kHz exceeding its linewidth at cryogenic temperatures. The extreme flexibility of the laser writing process allows for a direct integration of the membrane into the microscopic cavity. The direct fiber coupling, its scaling capabilities to coupled resonator systems, and the potential implementation of dissipation dilution structures and integration of electrodes make it a promising platform for fiber-tip integrated accelerometers, optomechanically tunable multi-mode mechanical systems, or directly fiber-coupled systems for microwave to optics conversion.Comment: 10 pages, 5 figure

Cross-Coupling Reactions of Monosubstituted Tetrazines

A Ag-mediated Pd-catalyzed cross-coupling method for 3-bromo-1,2,4,5-tetrazine with boronic acids is presented. Electronic modification of the 1,1′-bis(diphenylphosphine)ferrocene (dppf) ligand was found to be crucial for good turnover. Using this fast method, a variety of alkyl-, heteroatom-, and halide-substituted aryl- and heteroaryl-tetrazines were prepared (29 examples, up to 87% yield)

Embolization with the Amplatzer Vascular Plug in TIPS Patients

Vessel embolization can be a valuable adjunct procedure in transjugular intrahepatic portosystemic shunt (TIPS). During the creation of a TIPS, embolization of portal vein collaterals supplying esophageal varices may lower the risk of secondary rebleeding. And after creation of a TIPS, closure of the TIPS itself may be indicated if the resulting hepatic encephalopathy severely impairs mental functioning. The Amplatzer Vascular Plug (AVP; AGA Medical, Golden Valley, MN) is well suited for embolization of large-diameter vessels and has been employed in a variety of vascular lesions including congenital arteriovenous shunts. Here we describe the use of the AVP in the context of TIPS to embolize portal vein collaterals (n = 8) or to occlude the TIPS (n = 2)

Activated particulate organic matter as a carbon source for denitrification in RAS.

Sustainable aquaculture supplies fish products to market to meet the increasing need of fish and fish products in human diet and industry. Recirculating aquaculture systems (RAS), in which there is constant reuse of water, offer an extremely resource-efficient way to produce fish. Yet, RAS also need a constant water filtration in order to achieve adequate water parameters and finally quality products. Efforts to increase the effectiveness of the nitrification biofilters and denitrification reactors and to decrease the amount of solid waste in form of fish faeces and waste diet from a RAS are central research topics in this field. The present study aimed: 1) To analyze how efficiently fish use the inputs to the RAS system and the content of what is lost (e.g. in fish faeces, foam, waste diet etc) within waste products from a RAS, 2) To determine if filtered particulate organic matter, otherwise disposed of as waste, may be used as carbon source in a recycling procedure within RAS and, 3) To evaluate the effectiveness of ozone-activated particulate organic matter when used by denitrification bacteria as external carbon source. An experiment was conducted in which individuals of European seabass Dicentrarchus labrax, kept in a RAS, were fed ad libitum with commercial feeds and the amount of solid waste (according to the feeds inputs) from the drum filter and the protein skimmer were determined, sampled before and after feeding and analyzed to examine their carbon, nitrogen and organic matter content (e.g. aminoacids, fatty acids) tested against the commercial feed used. Organic matter content was determined by gas chromatography and mass spectrometry. The sampled particulate organic matter from the drum filter was subsequently treated with ozone over various time intervals and its content analyzed to quantify simple carbon substrates feasible for use as carbon source by bacteria in the denitrification reactor. Ozone is commonly used for disinfection purpose and to clear the water from organic compounds responsible of the high turbidity of the water in RAS. It is as well toxic for living organism when higher levels leak to the system. The ozonized samples were tested against commercial carbon sources commonly used for RAS-denitrification at a laboratory scale with the aim of test it later on in a real system. The final objective is to evaluate the performance of denitrification reactors using ozone-activated particulate organic matter and to determine its influence on the growth performance of the studied species under these conditions as well as on the efficiency of the denitrification process. We expect to optimize RAS by recycling the particulate organic matter filtered out from the RAS and to find out the best ozone treatment time for obtaining an efficient denitrification and no collateral damage to the reared organisms or to the bacteria in denitrification reactors and nitrification biofilters. Preliminary results of this pilot study will be presented

Job Satisfaction and Chronic Stress of General Practitioners and Their Teams: Baseline Data of a Cluster-Randomised Trial (IMPROVEjob)

Background: A high prevalence of poor job satisfaction and high chronic stress is documented for general practitioners (GPs) and non-physician practice staff from various countries. The reasons are multifactorial and include deficits in leadership, communication and workflows. This publicly funded study evaluates the effectiveness of the newly developed participatory, interdisciplinary, and multimodal IMPROVEjob intervention on improving job satisfaction among GPs and practice personnel. Here, we report the baseline characteristics of the participating GPs and practice assistants, focusing on job satisfaction and perceived chronic stress. Methods: The IMPROVEjob study was performed as a cluster-randomised, controlled trial (cRCT) with German GP practices in the North Rhine Region. The IMPROVEjob intervention comprised two leadership workshops (one for practice leaders only; a second for leaders and practice assistants), a toolbox with supplemental printed and online material, and a nine-month implementation phase supported by IMPROVEjob facilitators. The intervention addressed issues of leadership, communication, and work processes. During study nurse visits, participants completed questionnaires at baseline and after nine months follow up. The primary outcome was the change in job satisfaction as measured by the respective scale of the validated German version of the Copenhagen Psychosocial Questionnaire (German COPSOQ, version 2018). Perceived chronic stress was measured using the Trier Inventory of Chronic Stress (TICS- SSCS). Results: Recruitment of 60 practices was successful: 21 were solo, 39 were group practices. At baseline, n = 84 practice owners, n = 28 employed physicians and n = 254 practice assistants were included. The mean age of all participants was 44.4 (SD = 12.8). At baseline, the job satisfaction score in the total sample was 74.19 of 100 (±14.45) and the perceived chronic stress score was 19.04 of 48 (±8.78). Practice assistants had a significantly lower job satisfaction than practice owners (p < 0.05) and employed physicians (p < 0.05). In the regression analysis, perceived chronic stress was negatively associated with job satisfaction (b= -0.606, SE b = 0.082, p < 0.001, ICC = 0.10). Discussion: The degree of job satisfaction was similar to those in other medical professionals published in studies, while perceived chronic stress was markedly higher compared to the general German population. These findings confirm the need for interventions to improve psychological wellbeing in GP practice personnel

Twenty-year outcome and association between early treatment and mortality and disability in an inception cohort of patients with rheumatoid arthritis: Results from the Norfolk Arthritis Register

Objective – To describe the outcome of patients with rheumatoid arthritis (RA) over 20 years from symptom onset; to assess the association between early treatment (DMARDs/steroids) and mortality and disability over follow-up. Methods – Patients from the Norfolk Arthritis Register recruited from 1990-94 who met the 2010 ACR/EULAR RA criteria at baseline were included in this analysis. Demographic/clinical variables were collected at baseline and years 1-3, 5, 7, 10, 15 and 20. Disease activity (swollen/tender joint counts (SJC/TJC)), disability (HAQ) and mortality over 20 years are described. Association between treatment group (early treatment (ET) = treatment ≤6 months after symptom onset; late treatment (LT) = treatment >6 months; never treatment (NT) = no treatment) and mortality and disability were assessed using weighted pooled logistic regression and weighted multilevel mixed-effects linear regression respectively. Inverse weights were used to account for indication/censoring confounding. Results – This study included 602 patients with RA (median (IQR) age = 56 (44, 68) years; 65.9% women). Median disease activity was low over follow-up (SJC 1-3, TJC 3-6). Median HAQ rose after year 1 but remained at low/moderate levels (median 1.25 after year 10). There was reduced mortality risk in the ET and LT compared to NT group. ET group had comparable HAQ to NT group over follow-up (β 0.03, 95% CI -0.06, 0.12); LT group had increased disability (LT vs NT β 0.10, 95% CI 0.02, 0.17). Conclusion – This study indicates the importance of early treatment regarding long-term outcomes of patients with RA. This article is protected by copyright. All rights reserved

Cardiovascular training improves fitness in patients with ankylosing spondylitis

Objective: Several studies suggest that patients with ankylosing spondylitis (AS) have an increased risk of cardiovascular disease. This study aimed to evaluate the effects of a 12-week individually heart rate-monitored, moderately intensive cardiovascular training on cardiovascular fitness and perceived disease activity in AS patients. Methods: Patients diagnosed with AS according to modified New York criteria were to either 'cardiovascular training' or 'attention control'. The training group performed three cardiovascular trainings per week. All participants attended one weekly usual care flexibility training. Attention control contained regular discussion groups on coping strategies. Adherence was self-monitored. Assessments were performed at baseline and after the intervention period of 3 months. Physical fitness was the primary endpoint, measured in watts using a submaximal bicycle test following the PWC75% protocol. All analyses controlled for gender, age, body mass index, baseline fitness and physical activity levels, and BASDAI. Results: Of 106 AS patients enrolled, 40% were women, mean age was 49 (SD +/-12) years. 76.5% of the training group reported exercising at least three times a week. At 3 month follow-up, fitness level in the training group was significantly higher than in the control group (90.32 (SD 4.52) vs.109.84 (SD 4.72) respectively, p=0.001), independent of other covariates. Average BASDAI total score was 0.31 points lower (p = 0.31) in the training group, reaching significance for the 'peripheral pain' subscore (1.19; p=0.01), but not for 'back pain' or 'fatigue'. Conclusions: Cardiovascular training, in addition to flexibility exercise, increased fitness in AS patients and reduced their peripheral pain

Systematic RNA-interference in primary human monocyte-derived macrophages: A high-throughput platform to study foam cell formation

Macrophage-derived foam cells are key regulators of atherogenesis. They accumulate in atherosclerotic plaques and support inflammatory processes by producing cytokines and chemokines. Identifying factors that regulate macrophage lipid uptake may reveal therapeutic targets for coronary artery disease (CAD). Here, we establish a high-throughput screening workflow to systematically identify genes that impact the uptake of DiI-labeled low-density lipoprotein (LDL) into monocyte-derived primary human macrophages. For this, monocytes isolated from peripheral blood were seeded onto 384-well plates, solid-phase transfected with siRNAs, differentiated in vitro into macrophages, and LDL-uptake per cell was measured by automated microscopy and quantitative image analysis. We applied this workflow to study how silencing of 89 genes impacts LDL-uptake into cells from 16 patients with CAD and 16 age-matched controls. Silencing of four novel genes (APOC1, CMTM6, FABP4, WBP5) reduced macrophage LDL-uptake. Additionally, knockdown of the chemokine receptor CXCR4 reduced LDL-uptake, most likely through a G-protein coupled mechanism that involves the CXCR4 ligand macrophage-induced factor (MIF), but is independent of CXCL12. We introduce a high-throughput strategy to systematically study gene function directly in primary CAD-patient cells. Our results propose a function for the MIF/CXCR4 signaling pathway, as well as several novel candidate genes impacting lipid uptake into human macrophages