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Background Increased cardiovascular risk has been suggested for selected autoimmune disorders. Yet, for many conditions, evidence is insufficient to design more targeted prevention measures and guide clinical decisions. Methods We used linked primary and secondary electronic health records from the Clinical Practice Research Datalink (CPRD) to assemble a cohort of individuals newly diagnosed with any of 19 autoimmune disorders between 01/01/2000 and 31/12/2017 and free of cardiovascular disorders (CVD) up to 12 months after diagnosis, and up to five individuals matched on age, sex and socioeconomic status, with follow-up until 30/06/2019. We investigated incidence of nine cardiovascular outcomes and used cox-proportional hazards models to examine differences in patients with and without autoimmune disorders accounting for known cardiovascular risk factors. Findings We identified 432,883 individuals with autoimmune disorders and 2,159,350 matched controls. Of these, 104,504 people with and 450,195 without autoimmune disorders developed incident CVD during a median of 5.3 [interquartile range: 2.6, 9.6] years of follow-up. Patients with one or more autoimmune disorders had higher risk of cardiovascular outcomes: adjusted hazard ratio (HR) [95% confidence interval (CI)] 1.34 [1.31, 1.37]. This relationship held for every individual cardiovascular disorder and increased progressively with the number of autoimmune disorders present. Among autoimmune disorders, those associated with systemic inflammation, such as type I diabetes (2.09 [1.91, 2.28]), systemic sclerosis (2.90 [2.29, 3.67]) and systemic lupus erythematosus (2.21 [1.96, 2.50]) presented with highest overall cardiovascular risk (Figure). Interpretation Autoimmune disorders are associated with a high risk of developing cardiovascular outcomes. These findings warrant targeted cardiovascular prevention measures for patients with autoimmune disorders and further research into pathophysiological mechanisms underlying these complications. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie (grant agreement No 843267) and from the European Society of Cardiology (grant number App000037070).

Background The peak of the global COVID-19 pandemic has not yet been reached, and many countries face the prospect of a second wave of infections before effective vaccinations will be available. After an initial phase of viral replication, some patients develop a second illness phase in which the host thrombotic and inflammatory responses seem to drive complications. Severe COVID-19 disease is linked to high mortality, hyperinflammation, and a remarkably high incidence of thrombotic events. We hypothesize a crucial pathophysiological role for the contact pathway of coagulation and the kallikrein-bradykinin pathway. Therefore, drugs that modulate this excessive thromboinflammatory response should be investigated in severe COVID-19. Methods In this adaptive, open-label multicenter randomized clinical trial, we compare low molecular weight heparins at 50 IU anti-Xa/kg twice daily—or 75 IU anti-Xa twice daily for intensive care (ICU) patients—in combination with aprotinin to standard thromboprophylaxis in hospitalized COVID-19 patients. In the case of hyperinflammation, the interleukin-1 receptor antagonist anakinra will be added on top of the drugs in the interventional arm. In a pilot phase, the effect of the intervention on thrombotic markers (D-dimer) will be assessed. In the full trial, the primary outcome is defined as the effect of the interventional drugs on clinical status as defined by the WHO ordinal scale for clinical improvement. Discussion In this trial, we target the thromboinflammatory response at multiple levels. We intensify the dose of low molecular weight heparins to reduce thrombotic complications. Aprotinin is a potent kallikrein pathway inhibitor that reduces fibrinolysis, activation of the contact pathway of coagulation, and local inflammatory response. Additionally, aprotinin has shown in vitro inhibitory effects on SARS-CoV-2 cellular entry. Because the excessive thromboinflammatory response is one of the most adverse prognostic factors in COVID-19, we will add anakinra, a recombinant interleukin-1 receptor antagonist, to the regimen in case of severely increased inflammatory parameters. This way, we hope to modulate the systemic response to SARS-CoV-2 and avoid disease progressions with a potentially fatal outcome. Trial registration The EU Clinical Trials Register 2020-001739-28. Registered on April 10, 2020.

Vanassche, T (corresponding author), Katholieke Univ Leuven, Dept Cardiovasc Sci, Ctr Mol & Vasc Biol, Leuven, Belgium. Univ Hosp Leuven, Dept Cardiovasc Sci, Leuven, Belgium. thomas.vanassche@uzleuven.be

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Background:Advances in therapeutics and treatment strategies for Rheumatoid Arthritis (RA) have improved clinical outcomes. Although these advances also impact the well-being as shown in many patient-reported outcomes, still a sizeable number of patients in clinical remission report a reduced well-being.Objectives:To explore factors that contribute to well-being in patients with early RA.Methods:Patients from the 2-year pragmatic treat-to-target Care in Early Rheumatoid Arthritis (CareRA) trial were included. Patients were treated intensively, with a combination of csDMARDs and glucocorticoid remission induction schemes, except one group treated with MTX monotherapy.Eight different validated questionnaires including the Arthritis Self-Efficacy Scale (ASES), the multidimensional Fatigue Inventory (MFI), the Pittsburgh Sleep Quality Index (PSQI) the Revised Illness Perception Questionnaire (IPQ-R), the Utrecht Coping List (UCL), the Short Form 36 (SF-36), RA Quality of Life questionnaire (RA-QOL) and the Social Support List (SSL) were taken. Questionnaires were obtained at baseline, at week 16, 52 and 104 except for the IPQ and UCL, which were only taken at baseline and week 16.Three patients` groups were created including all patients, patients in remission (DAS28crp < 2.6) and not in remission. Regression models were constructed to define well-being at week 16, 52 and 104. The Patient Global Assessment (PGA) on a Visual Analogue Scale 0-100 (VAS) was chosen as a proxy for well-being (score 0-100). As predictors, all subscales of the 8 validated questionnaires, summing to 84 variables, with and without the VAS for Pain (VAS-Pain) were used in 18 models (3 patient groups, 3 time points, with/without VAS-Pain) in total. Data reduction used forward, backward and stepwise selection based on the Aikake information criteria. Data was checked for influential observations by Cook’s distance and for multicollinearity by variance inflation factors (threshold = 5). Influential observations were removed one observation every time. Highly correlated variables were deleted by backward selection (α=5%). Missing data was handled by multiple imputation using CART with 15 iterations.Results:In total, 379 patients were included. Table 1 gives the number of variables and the associated R2. In the 9 models defining well-being without VAS-Pain, 53 variables were used at least once. Most common variables were bodily pain (n=8) and social function (n=5) of the SF-36, and positive emotions (n=4) of the SSL. In the 9 models with VAS-Pain, 31 variables were used at least once. Most common variables were vitality (n=3) and social function (n=3) of the SF-36, and identity (n=3) of the IPQ-R. Model content was heterogenous regarding patient population and time.R2and number of variables in each model of well-beingAll patientsPatients in remissionPatients not in remissionR2#R2#R2#week 1652%1339%753%6week 16 with VAS-Pain78%469%680%5week 5244%844%757%12week 52 with VAS-Pain84%584%692%2week 10440%1339%862%10week 104 with VAS-Pain81%782%486%11R2= coefficient of determination, the proportion of the variance in the dependent variable that is predictable from the independent variable(s). # = number of variables selected in regression modelConclusion:Well-being is apparently difficult to define uniformly as many factors contribute to it. As already known, well-being, defined by PGA, and VAS-Pain are highly associated, even in patients in remission where pain levels should be theoretically lower. Other well-being definitions could lead to different results and should be further explored.Disclosure of Interests:Diederik De Cock: None declared, Tianna Poffe: None declared, Geert Verbeke: None declared, Veerle Stouten: None declared, Sofia Pazmino: None declared, Delphine Bertrand: None declared, Johan Joly: None declared, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies

Concerns in regard to thermal discomfort experienced by cattle are increasing, especially in the summer time. It is important to determine whether or not pastured beef cattle would make use of shade during sunny circumstances in a temperate climate. If so, scientifically based guidelines may need to be formulated for translation into legislation aiming to protect animal welfare. Approximately 255 beef cattle on 18 pastures were observed from July 2010 through November 2010 in central Belgium. Pastures having either natural or artificial shelter for animal protection but similar with respect to agricultural and climatological characteristics were included in the study. The analysis of data focused on the effect of weather conditions on sheltering behavior of cattle, with pasture as a random factor. During sunny weather, ambient temperature had a significant influence on the use of shade (P0.0001): the greater the environmental temperature was, the more cattle on a pasture were located in a shaded area. Ambient temperature (Ta) and relative humidity (RH) both tended to have a positive relation with shade use. However, the expected impact of their combined effect was not found, probably because of the strong negative correlation between RH and Ta (r = -0.7122) in the studied region. Greater wind speed (WS) reduced the need for shade, even at a greater Ta (P0.0001). Both Ta and solar radiation (RAD) influenced use of shade, but the interaction or combined effect was not significant. The variability of shade use between the pastures in this study could be explained by the surface of shade present on the pasture. It is rather self-evident that cows made more use of shade when a greater percentage of the surface area was shaded, but the presence of remaining nonshaded area kept the alternative choice reliable. On the basis of the fact that more cattle being observed in a shaded area was associated with a higher dry air temperature, it can be concluded that providing shelter could also be valuable for pastured cattle living in a temperate region.

Surgical castration of male piglets without anesthesia is a routine management practice conducted on commercial pig farms. For animal welfare reasons, it would be beneficial to develop methods of practical pain relief. The objective of this study was to evaluate the effect of providing CO₂ anesthesia before castration on the behavior of piglets for up to 8 d after castration in comparison with piglets castrated without anesthesia. In 3 successive replicates, the behavior of 186 male piglets castrated with (n = 95) or without (n = 91) anesthesia was observed for up to 8 d after castration. All piglets in a given replicate were castrated on the same day, before 8 d of age. Behavioral observations were carried out in accordance with a continuous focal sampling procedure that began immediately after castration and continued for a period of 1 wk. Barrows anesthetized with CO₂ before castration displayed more interactive behaviors during the overall observation period than the other barrows (P = 0.0412), which may indicate better welfare. Assessing all observation periods separately, differences in activity at the udder, lying, walking, and interactive behaviors appeared to support the beneficial effect of providing CO₂ anesthesia before castration. However, these differences varied over time between treatment groups. The most important conclusion was that piglets castrated with or without CO₂ anesthesia displayed behaviors indicative of pain and discomfort for up to 6 d after castration. Therefore, additional analgesia may be necessary to eliminate the long-term pain caused by castration even in piglets anesthetized with CO₂ before castration.

We report a patient in whom 11 years after the treatment of a breast tumour, bilateral ovarian metastases were disclosed. Surgical exploration confirmed unique ovarian metastases within a 'clean' abdomen and pelvis. The particularities of this case compared with the literature are the rather long interval of 11 years and the fact that no other metastases were present. The literature indeed reveals that most of the patient with ovarian metastases are premenopausal, have bilateral involvement; the ovarian metastases occur within a few years and are frequently accompanied by other metastases.

Au moment ou la chronique precedente1 fut publiee, l’Aristoteles Latinus n’en etait plus a l’etat d’un simple projet. Six volumes etaient deja a la disposition des interesses; on etait donc en droit d’esperer que ce vaste projet, lance par K. Michalski et patronne depuis 1930 par l’Union Academique Internationale, serait un jour realise.

The photolithographic principle and know-how of controlling the optical characteristics of thermally evaporated pure bismuth layers have been combined in the development of a new silverless metal/photoresist composite film for professional photography. A correlation exists between the spectral distribution of the specular reflection density of these films and the packing density of the evaporated layers. The photographic performance profile is also discussed.

The relative rates of hydrogen and deuterium abstraction by chlorine atoms from H2–D2, CH4–CD4, and C2H6–C2D6 in direct competition have been studied by a mass spectrometer technique permitting direct determinations of rates. The pair CHCl3–CDCl3 was investigated by a substitution—addition competition with C2Cl4. Data were obtained between 300° and 475°K, and values of kH/kD ranged between 3.64 and 10.9 for CH4/CD4, 2.37 to 2.69 for C2H6/C2D6, 1.58 to 2.26 for CHCl3/CDCl3, and 4.7 to 8.9 for H2/D2. For the family of reactions involving C–H–Cl, an extensive series of model calculations were made by the ``bond‐energy—bond‐order'' method. The expected variation of activation energy with heat of reaction was computed and compared with experiment. The expected variation of kinetic isotope effect with both temperature and heat of reaction was computed for a range of conditions much wider than these experiments. Simple activated complex theory predicts several strong trends of kinetic isotope effect with heat of...

The goal of this development was a stationary, standby, diesel engine alternator set in the 20 to 30kW capacity range that can be applied in telephone offices without the need for a dedicated engine room. It was further desired to minimize the effort of application engineering, installation and building modification for this set. The result of the development is an automatic engine alternator set utilizing a lightweight, high-speed, automotive diesel engine in a vertical configuration. Included in the set's enclosure are transfer switch control; meters and alarms; starting and control batteries and their rectifiers; output circuit breaker; fuel handling system that will take fuel directly from a buried tank; radiator cooling system; and exhaust gas silencer system. The set is contained in a sound attenuating enclosure that is 34" wide, 36" deep and 85" high. The set does not consume either room air or add any significant heat load to the room.