Search

Despite the multiple and convincing evidence of the existence of dark matter (DM) in our Universe, its detection is one of the most pressing questions in particle physics. As of today, there is no unambiguous hint which could clarify the particle nature of DM. For these reasons, a huge experimental effort is ongoing, trying to realize experiments which can probe the particle properties of DM. In particular, direct search experiments are trying to cover the largest possible mass range, from a few MeVs up to TeVs. Particularly suited for the sub-GeV mass region are detectors containing light nuclei, which are sensitive to the scattering of light DM candidates. Among them, we investigate a carbon-based absorber to explore DM masses down to the MeV region. Thanks to their cryogenic properties (high Debye temperature and long-lived phonon modes), carbon-based materials operated as low temperature calorimeters could reach an energy threshold in the eV range and would allow for the exploration of new parameters of the DM–nucleus cross section. Despite several proposals, the possibility of operating a carbon-based cryogenic detector is yet to be demonstrated. In this contribution, the preliminary results obtained with a diamond absorber operated with a TES temperature sensor will be reported. The potential of such a detector in the current landscape of DM searches will also be illustrated.

BackgroundEnvironmental air pollution has been associated with disruption of the immune system at a molecular level.ObjectivesThe primary aim of the present study is to describe the association between long-term exposure to air pollution and risk of developing immune-mediated conditions.MethodsWe conducted a retrospective observational study on a nation-wide dataset of women and men. Diagnoses of various immune-mediated diseases were retrieved. Data on the monitoring of PM10 and PM2.5 concentrations were retrieved from the Italian institute of environment protection and research (ISPRA). The long-term average PMs concentrations were the exposure of interest. Every study subject was linked to a PMs exposure value, which resulted from the average concentration of urban, rural and near-traffic stations of the subject residency from January 2013 to November 2020. Patients were linked to the nearest air quality station through ZIP code centroids. Generalized linear models were employed to determine the relationship between autoimmune diseases prevalence and PM. The fully adjusted model included age, body mass index (BMI), menopause, glucocorticoid treatment, treatment with adjuvant hormone therapy for breast or prostate cancer, specialty of the physician that entered the data and macro-area of residency (stratified as a categorical variable: northern Italy, central Italy and southern Italy.Results81,363 subjects were included in the study. We found a positive association between PM10 and the risk of autoimmune diseases (ρ +0.007, p 0.014). Every 10 µg/m3 increase in PM10 concentration was associated with an incremental 7% risk of having autoimmune disease. Exposure to PM10 above 30 µg/m3 and PM2.5 above 20 µg/m3 was associated with a 12% and 13% higher risk of autoimmune disease pooled together, respectively (aOR 1.12, 95% CI 1.05-1.20 and aOR 1.13, 95% CI 1.06-1.20). Exposure to PM10 was associated with an increased risk of rheumatoid arthritis (aOR 1.408, 95% CI 1.271-1.560) but no other autoimmune diseases, whereas exposure to high levels of PM2.5 were associated with an increased risk of rheumatoid arthritis (aOR 1.559, 95% CI 1.401-1.734), CTDs (aOR 1.147, 95% CI 1.024-1.286) and IBDs (1.206, 95% CI 1.028-1.415) but no other autoimmune diseases.ConclusionLong-term exposure to air pollution was associated with higher risk of developing autoimmune diseases, in particular rheumatoid arthritis, CTDs and IBD. Chronic exposure to levels above the threshold for human protection was associated with a 10% higher risk of developing immune-mediated diseases.Disclosure of InterestsGiovanni Adami Shareholder of: Galapagos, Theramex, Marco Pontalti: None declared, Camilla Benini: None declared, Angelo Fassio: None declared, Eugenia Bertoldo: None declared, Davide Gatti: None declared, Maurizio Rossini Shareholder of: Abbvie, Amgen, Bms, Eli Lilly, Galapagos, Novartis, Pfizer, Sandoz, Theramex, Ucb.

BackgroundScar imaging echocardiography with ultrasound multi-pulse scheme (eSCAR) is a novel technique allowing detection of myocardial scars. eSCAR has never been explored in patients with systemic sclerosis (SSc).ObjectivesThe aim of our study was to examine whether eSCAR may detect subclinical myocardial fibrosis in SSc.MethodsIn this cross-sectional study conducted between 11/2020 and 02/2021, consecutive SSc patients from the University of Verona underwent cardiovascular disease (CVD) screening procedures including standard transthoracic echocardiography (TTE) and myocardial scars detection through the eSCAR technique. We excluded patients with prior history of structural heart disease and pulmonary hypertension. To validate eSCAR findings, we assessed myocardial function through global longitudinal strain (GLS) analysis by speckle tracking echocardiography (STE). We also conducted a case-control study comparing eSCAR findings in randomly selected SSc patients and non-SSc controls matched 1:1 for age, sex and number of CVD risk factors. The primary outcome was the proportion of patients with myocardial scars. Principal component analysis (PCA) was used to determine main eSCAR patterns. Multivariable linear regression analysis was used to minimise confounding.ResultsScar imaging echocardiography revealed that 42/92 (44%) SSc patients had myocardial scars involving a median [25th-75th percentile] of 4 [1-7] segments. PCA identified that myocardial scars localised mostly at the inferior and septal segments (inferoseptal pattern; Figure 1). STE validation confirmed that GLS was significantly reduced in SSc patients with inferoseptal scars (Table 1). Otherwise, all standard echocardiography measures were normal in both groups. In multivariable regression analysis, prior digital ulcerations (B=0.41, 95% CI 0.008 to 0.809, p=0.045) and body mass index (B=-0.06, 95% CI -0.113 to -0.015, p=0.012) were both significantly and independently associated with inferoseptal myocardial scars. Myocardial scars were found in 38% of SSc patients and no matched controls (pTable 1.Comparison of speckle tracking echocardiography (longitudinal myocardial strain) in eSCAR-positive (inferoseptal pattern) and eSCAR-negative (no inferoseptal pattern) patients.Speckle tracking echocardiographyeSCAR-positive (n= 8)eSCAR-negative (n=31)P-valueGLS global (%)- 20.24 (2.39)- 20.42 (3.65)0.895GLS 4-chambers (%)- 20.66 (1.91)- 20.09 (4.12)0.720GLS 2-chambers (%)- 23.02 (5.23)- 21.97 (3.89)0.924GLS 3-chambers (%)- 17.11 (2.60)- 19.31 (5.26)0.015GLS apical- anterior- 19.60 (6.12)- 17.72 (4.42)0.857- inferior- 26.89 (7.79)- 23.65 (5.46)0.581- lateral- 18.91 (2.04)- 18.13 (5.12)0.508- septal- 22.68 (7.14)- 21.76 (7.04)0.844GLS basal- anterior- 23.35 (3.82)- 22.75 (8.36)0.752- anteroseptal- 14.09 (4.74)- 18.66 (7.46)0.109- inferior- 22.69 (8.49)- 22.78 (6.94)0.818- lateral- 19.99 (7.68)- 22.55 (7.01)0.218- septal- 14.26 (4.63)- 18.07 (8.79)0.081GLS mid- inferior- 23.09 (6.12)- 22.58 (5.07)0.917- septal- 14.80 (5.69)- 17.50 (7.53)0.056- anterior- 20.54 (3.28)- 19.73 (6.520.026- anteroseptal- 14.70 (4.96)- 18.13 (5.20)0.010- lateral- 18.64 (5.79)- 20.09 (5.73)0.270Data are reported as mean (S.D.). GLS, global longitudinal strain.Figure 1.ConclusionThis simple ultrasound technique allows detection of myocardial dysfunction associated with scars in SSc patients, or its absence in matched controls. Patients with prior digital ulcerations and low body weight have the strongest association with inferoseptal myocardial scars. eSCAR may help detect subclinical myocardial fibrosis in SSc.Disclosure of InterestsNone declared

BackgroundSarcopenia is a progressive and generalized skeletal muscle loss associated with falls, fractures, physical disability, and mortality, described as age-related or secondary. Systemic inflammatory diseases, such as rheumatoid arthritis (RA), are well-known causes of secondary sarcopenia. However, the exact prevalence of sarcopenia in patients with RA is still unknown, partly due to the heterogeneous definitions of sarcopenia adopted in different studies.ObjectivesTo assess the prevalence of sarcopenia in a cohort of patients affected by RA, and to evaluate the influence of age, sex, comorbidity, disease duration and activity, antibody status and therapies on sarcopenia.MethodsWe conducted a retrospective observational study on adult patients affected by RA undergoing evaluation at our outpatient clinic from January 2009 and July 2021. All patients underwent dual-energy X-ray absorptiometry (DXA) for assessment of body composition; diagnosis of sarcopenia was defined using Skeletal Muscle Mass Index (SMI), as proposed by consensus EWGSOP2 (1). We collected relevant demographic, clinical, therapeutic, and laboratory data at the time of DXA. We excluded patients affected by neoplastic disorders and/or malnutrition. Binary logistic regression analysis was employed to define predictors and protective factors of developing sarcopenia.ResultsA total of 266 patients (82.7% women) with a median age of 58.4 (IQR 14.4) years were included in the study. The prevalence of sarcopenia was 27.44%. From the binary logistic regression analysis, we found that the use of oral glucocorticoids (GCs) at a daily dose > 3.25 mg of prednisone-equivalent was significantly associated with sarcopenia (β 0.68, p = 0.047, aOR 1.98, 95% CI 1.009 – 3.881) (Figure 1). We found a significant inverse correlation between conventional disease-modifying antirheumatic drug (c-DMARDs) and sarcopenia (β -0.71, p = 0.027) as well. Age, sex, disease duration, mean disease activity - expressed as disease activity score based on 28 joints (DAS-28), erosive and seropositive disease - and biologic disease-modifying antirheumatic drug (b-DMARDs) therapy were not predictors of sarcopenia, albeit seropositive status showed a correlation trend with increased prevalence of sarcopenia (p = 0.092).Figure 1.ConclusionOur study showed that sarcopenia is a common complication in RA. Glucocorticoid therapy was associated with an increased prevalence of sarcopenia, while c-DMARDs acted as protective factors, possibly decreasing chronic inflammation. No correlation was found with b-DMARDs, possibly due to association with longer and more aggressive rheumatic disease.References[1]Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48:16–31Disclosure of InterestsNone declared

BackgroundSystemic Sclerosis (SSc) is an autoimmune disease characterized by vasospasm and microvascular involvement. Iloprost (ILO), a prostaglandin analogous, is used for the treatment of SSc-related Raynaud’s Phenomenon and digital ulcers. The indicated dosage is 0-5-2 ng/kg/min for 6-8 hours and the maximum dose is decided upon the patient’s tolerance.ObjectivesOur study aims to analyse ILO infusion tolerance and possible predictive factors in patients with SSc.MethodsWe evaluated patients with SSc beginning ILO iv treatment between 2004 and 2021. We assessed the maximum tolerated ILO iv infusion rate, the incidence of adverse events (AEs) and the need for symptomatic therapy during the dose-finding sessions. We collected relevant demographic and medical data at the beginning of ILO iv treatment. Statistical analysis were performed to assess possible predictors of maximum tolerated ILO infusion rate and AEs.ResultsWe retrospectively analysed 113 patients. The median ILO infusion rate at the end of the dose-finding process was 0.88 ng/kg/min (IQR 0.37). We found a significant inverse correlation between ILO infusion rate and body mass index (BMI) at the beginning of treatment. BMI was negatively associated with ILO infusion rate (β -0.29, p = 0.001) after correction for relevant confounding factors. Subjects in the upper BMI tertile (BMI above 25) had a lower tolerance to ILO compared with subjects in the lower BMI tertile BMI below 22 (p=0.002). Disease pattern, disease duration, age at the onset of disease, mean blood pressure, gender, smoking habits, combination therapy with calcium channel blocker or endothelin inhibitors were not predictors of ILO tolerance. AEs during ILO titration occurred in 47.8% of patients, of whom 22.2% presented concomitant hypotension. The most common AEs were headache, nausea, vomiting, diarrhoea, oedema, hypotension, and symptomatic therapy was needed in half of the patients at least once. Overweight patients (BMI >26) presented a 13-fold increased risk of developing AEs during ILO titration (adjusted odd ratio 13.979 95% CI 2.359-82.845).ConclusionOur study showed that only a higher BMI was associated with lower ILO infusion rate tolerance and higher AEs rate, underlying a possible BMI-dependent endothelial dysfunction possibly mediated by endothelin receptor expression. Individual ILO regimens still need to be tailored to the patient.Disclosure of InterestsNone declared

BackgroundSo far, few studies provided detailed data for the incidence of disease flare after the vaccination against Coronavirus (Covid)-19 in patients with psoriatic arthritis (PsA). Results from small cohorts report an incidence of flares after Covid-19 vaccination of 0-7.7% and disease activity does not seems to be influenced by Covid-19 vaccination in patients with PsA. However, since PsA is a highly fluctuating disease with prolonged remission and irregular reactivation, it is difficult to establish a causal relationship between the Covid-19 vaccination and disease flares.ObjectivesTo define the impact of Covid-19 vaccination and disease activity on the incidence of disease flare in patients with psoriatic arthritis (PsA).MethodsWe prospectively evaluated patients with PsA in remission or low-disease activity candidate to receive Covid-19 vaccination with mRNA vaccines, collecting demographic, clinical, and therapeutic data and assessing DAPSA 28, PCR before and after vaccination. We assessed flares using patients and clinician concordance. We retrospectively evaluated flare incidence in the same timeframe of the previous year. We performed statistical analysis to find possible predictors of flares after vaccination.ResultsA total of 57 patients with PsA were prospectively evaluated, and retrospective analysis was possible for 53 of them. DAPSA 28 and CRP did not differ significantly before and after the vaccination. The incidence of flares in the two periods (2020 vs 2021) did not differ significantly (18.8% vs 8.8%, p=0.166). We found a higher basal mean DAPSA 28 in patients who flared up after vaccination (7.3 vs 4.1, p-value 0.046). Only having a flare in the previous year was associated with a higher chance of recurrence after Covid-19 vaccination (p=0.02) in the logistic regression analysis, while other predictors (age, gender, disease activity, ongoing DMARD therapy, ongoing bDMARD therapy) did not.ConclusionOur findings suggest that, in patients with PsA, disease activity could be the main driver of disease flares rather than Covid-19 vaccination.References[1]Furer V, Eviatar T, Zisman D, et al. Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study. Ann Rheum Dis. 2021, 10:1330-1338.[2]Geisen UM, Berner DK, Tran F, et al. Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort. Ann Rheum Dis. 2021, 10:1306-1311.[3]Machado PM, Lawson-Tovey S, Strangfeld A, et al. Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry. Ann Rheum Dis 2021 Epub ahead of print.[4]Braun-Moscovici Y, Kaplan M, Braun M, et al (2021) Disease activity and humoral response in patients with inflammatory rheumatic diseases after two doses of the Pfizer mRNA vaccine against SARS-CoV-2. Ann Rheum Dis 80:1317–1321.[5]Spinelli FR, Favalli EG, Garufi C, et al. Low frequency of disease flare in patients with rheumatic musculoskeletal diseases who received SARS-CoV-2 mRNA vaccine. Arthritis Res Ther 2022, 24:21.Disclosure of InterestsNone declared

BackgroundEnvironmental air pollution has been associated with disruption of bone health at a molecular level. Particulate matter (PM) exposure can simultaneously stimulate bone resorption and halt bone formation.ObjectivesThe primary aim of the present study is to describe the association between long-term exposure to PM and osteoporosis in a large cohort of women at high risk of fracture.MethodsClinical, demographic and densitometric data were extracted from the DeFRAcalc79 dataset, which gathers data on women at risk for osteoporosis. Data on the monitoring of PM10 and PM2.5 concentrations were retrieved from the Italian institute of environment protection and research (Istituto Superiore per la Protezione e la Ricerca Ambientale, ISPRA). Every study subject was linked to a PM exposure value, which resulted from the average concentration of urban, rural and near-traffic stations of the subject residency (ZIP code centroids 25 km) from January 2013 to December 2019. Generalized linear models with robust estimators were employed to determine the relationship between BMD and PM long-term exposure. We sequentially adjusted for confounders. Model 1 included age, body mass index (BMI), presence of prevalent fragility fractures, family history of vertebral or hip fractures, and menopause. Model 2 was further adjusted for glucocorticoid treatment and comorbidities. Model 3 (main model) added to model 2 the macro-area of residency (stratified as a categorical variable: northern Italy, central Italy and southern Italy).Results59,950 women from 110 Italian provinces were included in the study. PM 2,5 exposure was negatively associated with T-score levels at the femoral neck (β -0.005, 95 CI -0.007 to -0.003) and lumbar spine (β -0.003, 95% CI -0.006 to -0.001). Chronic exposure to PM2.5 above 25 μg/m3 was associated with a 16% higher risk of having osteoporotic T-score at any site (aOR 1.161, 95% CI 1.105 to 1.220), exposure to PM10 above 30 μg/m3 was associated with a 15% higher risk of having osteoporotic T-score at any site (aOR 1.148, 95% CI 1.098 to 1.200).ConclusionLong-term exposure to air pollution was associated with higher risk of osteoporosis. Femoral neck site seemed to be more susceptible to the detrimental effect of PM exposure than lumbar spine site.Disclosure of InterestsGiovanni Adami Shareholder of: Galapagos, Theramex, Camilla Benini: None declared, Angelo Fassio: None declared, Eugenia Bertoldo: None declared, Ombretta Viapiana: None declared, Davide Gatti: None declared, Maurizio Rossini Shareholder of: Abbvie, Amgen, Bms, Eli Lilly, Galapagos, Novartis, Pfizer, Sandoz, Theramex, Ucb.

BackgroundThe effects of cholecalciferol supplementation on the regulation of inflammatory cytokines are still unclear.ObjectivesThis is a preliminary analysis on exploratory outcomes the DIBA/11 RCT [1,2] and aimed to compare the effects on serum inflammatory cytokines of three different regimes of cholecalciferol supplementation in vitamin D-deficient subjects.MethodsWe evaluated, in healthy subjects affected by vitamin D deficiency (defined as 25OHDSerum TNFα, interleukin-6 (IL6), interleukin-17 (IL17) and interleukin-10 (IL10) were dosed at baseline, Day 28, 53, 84 and 112. This study was approved by the institutional research committee (protocol identification: DIBA/11,EudraCT Number:2017-000194-36). Supported by Abiogen Pharma, Italy).ResultsA total of 75 subjects were randomized to receive one supplementation regimen. The descriptive of the sample at baseline and relative cytokines levels at the various observation points are reported in Table 1. The absolute changes of IL6, IL17 and IL10 are depicted in Figure 1. No significant differences were found among the three groups. TNFα was undetectable at baseline and at any time point.Table 1.anthropometrics and laboratory parameters at baseline (mean values ± standard deviation)ParameterAll patients (N=75)Daily 10.000 Ui(N = 25)Weekly 50.000 Ui(n = 25)Biweekly 100.000 Ui(N = 25)p-value (ANOVA)M:F31:4412:137:1812:13NSAge (years)34.1 ± 10.230.2 ± 9.936.7 ± 8.735.4 ± 11.00.059Body Weight (kg)66.7 ± 12.465.8 ± 13.267.8 ± 10.866.6 ± 13.7NSBMI23.1 ± 2.622.55 ± 2.723.8 ± 2.222.8 ± 2.7NSBaseline 25OHD (ng/mL)13.5 ± 3.714.6 ± 3.912.8 ± 313.5 ± 4.1NSBaseline IL-6 (pg/mL)1.3 ± 1.20.9 ± 0.61.4 ± 1.61.6 ± 1.3NSBaseline IL-17 (pg/mL)0.4 ± 1.80.7 ± 30.2 ± 1.10.2 ± 0.7NSBaseline IL-10 (pg/mL)0.9 ± 0.90.8 ± 0.71.2 ± 1.20.8 ± 0.7NSFigure 1.absolute changes of IL17, IL6 and IL10. *pConclusionIn the overall cohort we found slight decreases in serum IL6 and IL17 serum levels. No differences were found among groups.References[1]Fassio A, Adami G, Rossini M, et al. Pharmacokinetics of Oral Cholecalciferol in Healthy Subjects with Vitamin D Deficiency: A Randomized Open-Label Study. Nutrients. 2020;12(6).[2]Fassio A, Gatti D, Rossini M, et al. Pharmacodynamics of Oral Cholecalciferol in Healthy Individuals with Vitamin D Deficiency: A Randomized Open-Label Study. Nutrients. 2021;13(7):2293.Disclosure of InterestsAngelo Fassio: None declared, Davide Gatti Speakers bureau: Amgen, Celgene Eli-Lilly, MSD-Italia, Organon, UCB., Paid instructor for: Amgen, Celgene Eli-Lilly, MSD-Italia, Organon, UCB., Matteo Gatti: None declared, Maurizio Rossini Speakers bureau: Abiogen, Amgen, Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Grunenthal, MSD, Novartis, Pfizer, Sanofi, Sandoz, Theramex, UCB., Eugenia Bertoldo: None declared, Giovanni Adami: None declared

In this work, a first cryogenic characterization of a scintillating $$\hbox {LiAlO}_{2}$$ LiAlO 2 single crystal is presented. The results achieved show that this material holds great potential as a target for direct dark matter search experiments. Three different detector modules obtained from one crystal grown at the Leibniz-Institut für Kristallzüchtung (IKZ) have been tested to study different properties at cryogenic temperatures. Firstly, two 2.8 g twin crystals were used to build different detector modules which were operated in an above-ground laboratory at the Max Planck Institute for Physics (MPP) in Munich, Germany. The first detector module was used to study the scintillation properties of $$\hbox {LiAlO}_{2}$$ LiAlO 2 at cryogenic temperatures. The second achieved an energy threshold of ($$213.02\pm 1.48$$ 213.02 ± 1.48 ) eV which allows setting a competitive limit on the spin-dependent dark matter particle-proton scattering cross section for dark matter particle masses between $$350\,\hbox {MeV/c}^{2}$$ 350 MeV/c 2 and $$1.50\,\hbox {GeV/c}^{2}$$ 1.50 GeV/c 2 . Secondly, a detector module with a 373 g $$\hbox {LiAlO}_{2}$$ LiAlO 2 crystal as the main absorber was tested in an underground facility at the Laboratori Nazionali del Gran Sasso (LNGS): from this measurement it was possible to determine the radiopurity of the crystal and study the feasibility of using this material as a neutron flux monitor for low-background experiments.

A search for resonant absorption of solar axions by $^{169}$Tm nuclei was carried out. A newly developed approach involving low-background cryogenic bolometer based on Tm$_3$Al$_5$O$_{12}$ crystal was used that allowed for significant improvement of sensitivity in comparison with previous $^{169}$Tm based experiments. The measurements performed with $8.18$ g crystal during $6.6$ days exposure yielded the following limits on axion couplings: $|g_{A\gamma} (g_{AN}^0 + g_{AN}^3) \leq 1.44 \times 10^{-14}$ GeV$^{-1}$ and $|g_{Ae} (g_{AN}^0 + g_{AN}^3) \leq 2.81 \times 10^{-16}$., Comment: 7 pages, 5 figures

To cope with the foreseen demand for tungsten-based TESs in the current and future phases of the CRESST experiment, we investigated the possibility to implement a reliable, simple and reproducible fabrication method using sputtering. In this contribution, we present the method under development for tungsten deposition using conventional magnetron sputtering with xenon as sputtering gas. TESs with transition temperatures ($$T_c$$Tc) down to 15 mK have been obtained with transition widths smaller than 1 mK. We also give a first assessment on the reproducibility of the process and present the potential for tuning of the $$T_c$$Tc.

A newly developed experimental technique based on 169Tm-containing cryogenic bolometer detector was employed in order to perform the search for solar axions. The inclusion of target material into the active detector volume allowed for significant increase in sensitivity to axion parameters. A short 6.6 days measurement campaign with 8.18 g detector crystal yielded the following limits on axion couplings: | g A γ ( g A N 0 + g A N 3 ) ≤ 1.44 × 10 − 14 GeV − 1 and | g A e ( g A N 0 + g A N 3 ) ≤ 2.81 × 10 − 16 . The achieved results demonstrate high scalability potential of presented experimental approach.

Cryogenic Rare Event Search with Superconducting Thermometers (CRESST) is a long-standing direct dark matter detection experiment with cryogenic detectors located at the underground facility Laboratori Nazionali del Gran Sasso in Italy. CRESST-III, the third generation of CRESST, was specifically designed to have a world-leading sensitivity for low-mass dark matter (DM) (less than 2 GeV/$$\hbox {c}^{2}$$c2) to probe the spin-independent DM-nucleus cross section. At present, a large part of the parameter space for spin-independent scattering off nuclei remains untested for dark matter particles with masses below few GeV/$$\hbox {c}^{2}$$c2 although many motivated theoretical models having been proposed. The CRESST-III experiment employs scintillating $$\hbox {CaWO}_{{4}}$$CaWO4 crystals of $$\sim$$∼ 25 g as target material for dark matter interactions operated as cryogenic scintillating calorimeters at $$\sim$$∼ 10 mK. CRESST-III first data taking was successfully completed in 2018, achieving an unprecedented energy threshold for nuclear recoils. This result extended the present sensitivity to DM particles as light as $$\sim$$∼ 160 MeV/$$\hbox {c}^{2}$$c2. In this paper, an overview of the CRESST-III detectors and results will be presented.

The $^{169}$Tm nuclide has first nuclear level at 8.41 keV with magnetic type transition to the ground state and, therefore, can be used as a target nucleus for the search of resonant absorption of solar axions. We plan to use a Tm-containing crystal of a garnet family Tm$_3$Al$_5$O$_{12}$ as a bolometric detector in order to search for the excitation of the first nuclear level of $^{169}$Tm via the resonant absorption of solar axions. With this perspective in mind, a sample of the Tm$_3$Al$_5$O$_{12}$ crystal was grown and tested for its bolometric and optical properties. Measurements of chemical and/or radioactive contaminations were performed as well. In this paper we present the test results and estimate the requirements for a future low-background experimental setup., Comment: 9 pages, 6 figures, 3 tables

In this work, we want to highlight the potential of lithium as a target for spin-dependent dark matter search in cryogenic experiments, with a special focus on the low-mass region of the parameter space. We operated a prototype detector module based on a $$\hbox {Li}_2\hbox {MoO}_4$$ target crystal in an above-ground laboratory. Despite the high background environment, the detector sets a competitive limit on spin-dependent interactions of dark matter particles with protons and neutrons for masses between $$0.8~\hbox {GeV/c}^2$$ and $$1.5~\hbox {GeV/c}^2$$ .

Background:Environmental air pollution has been linked to the pathogenesis of Rheumatoid Arthritis (RA). Nevertheless, evidence linking higher concentrations of air pollutants with the risk of RA reactivations is missing.Objectives:The objective of the present study was to determine the association between RA flares and air pollution.Methods:We collected longitudinal data of patients affected by RA and of the daily concentration of air pollutants in the Verona area. We designed a case-crossover study. In case-crossover studies, instead of obtaining information from two groups (cases and controls), the exposure information is obtained comparing two different periods of time in the same group of patients followed longitudinally. We compared the exposure to pollutants in the 30-day and 60-day periods preceding an arthritic flare referent to the 30-day and 60-day preceding a low-disease activity visit. Flare was defined as an increase in DAS28-CRP of >1.2 points with current DAS28-CRP ≥3.2 (OMERACT definition).Results:888 patients with RA with 3,396 follow-up visits were included in the study. 13,636 daily air pollution records were retrieved. We found an exposure-response relationship between the concentration of air pollutants and the risk of having abnormal CRP levels (Figure 1). Patients exposed to greater concentrations of air pollutants were at higher risk of having CRP levels ≥5 mg/L. Patients exposed to PM10 concentrations ≥50 μg/m3 had a 70% higher risk of having CRP levels ≥5 mg/L (OR 1.696 95% CI, 1.245-2.311). Among RA patients, 440 patients (49.5%) had at least 2 follow-up visits with a difference in DAS28-CRP of more than 1.2 points (with current DAS28-CRP ≥3.2), serving as our sample for the case-crossover study. Concentrations of CO, NO, NO2, NOx, PM10, PM2.5 and O3 were higher in the 60-day period preceding a flare (Table 1). Sensitivity analyses considering geometric mean and cumulative concentrations yielded similar results (data not shown). Remarkably, we found that the cumulative exposure to NO2 in the 60 days preceding a flare was approximately 500 µg/m3 higher than the low disease activity visit, an exposure that equates to approximately to 200 passively smoked cigarettes (3.5 cigarettes per day on a 60-day period).Table 1.Case-crossover study. Mean concentrations (mean and Area Under the Curve) of air pollutants in the 60 days before low-disease activity visit and flare visit (DAS28-CRP difference >1.2)PollutantControl period (low disease activity, n=440)Hazard period (flare, n=440)p valueCO μg/m3Mean0.380.420.001AUC22.0024.530.001NO μg/m3Mean19.2324.110.002AUC1,120.531,403.880.002NO2μg/m3Mean30.9132.440.042AUC1,800.961,892.050.040NOxμg/m3Mean60.3469.350.004AUC3,515.774,041.060.004PM10 μg/m3Mean31.2133.650.011AUC1,789.221,942.520.005O3μg/m3Mean31.0833.790.002AUC1,776.371,934.350.001PM2.5 μg/m3Mean23.0824.740.018AUC1,272.611,403.60Figure 1.Odds of having abnormal CRP serum levels (≥5 mg/L) at different exposures of PM10 and PM2.5 (mean concentration in the 60 days before assessment)Conclusion:We found a striking association between air pollution and RA disease severity and reactivations in a cohort of patients followed over a 5-year period. The exposure to high levels of air pollutants was associated with increased CRP levels and a higher risk of experiencing a flare of arthritis. This excessive risk was evident at very low levels of exposure, even below the proposed threshold for the protection of human health. Our study has important and direct consequences. In order to reduce the burden of RA, public and environmental health policy makers should aim to diminish gaseous and PM emissions to a larger extent as currently recommended.Disclosure of Interests:None declared

The CRESST-III experiment searches for direct interactions of dark matter with ordinary matter. The main event signature would be a nuclear recoil inside one of the scintillating CaWO4 crystals. Operating the crystals as cryogenic calorimeters provides a phonon signal as measure of the deposited energy. The simultaneous readout of both signals is used to actively discriminate backgrounds. CRESST-III focuses on the sub-GeV/c2 mass region where the sensitivity is driven by the threshold. In the first data taking campaign of CRESST-III from 2016-2018 an unprecedented low threshold of 30.1 eV for nuclear recoils was obtained. In this contribution, we will report the status of the experiment and the latest results.

In the current direct dark matter search landscape, the leading experiments in the sub-GeV mass region mostly rely on cryogenic techniques which employ crystalline targets. One attractive type of crystals for these experiments is those containing lithium, due to the fact that $$^7\hbox {Li}$$7Li is an ideal candidate to study spin-dependent dark matter interactions in the low mass region. Furthermore, $$^6\hbox {Li}$$6Li can absorb neutrons, a challenging background for dark matter experiments, through a distinctive signature which allows the monitoring of the neutron flux directly on site. In this work, we show the results obtained with three different detectors based on $$\hbox {LiAlO}_2$$LiAlO2, a target crystal never used before in cryogenic experiments.

The original version of this article unfortunately contains mistakes.

Background Therapy of oligoarticular JIA is based on intrarticular injections of steroids, methotrexate and biotechnological therapy. ANAs-positive oligoarticular JIA patients with an early onset of disease have a consistent risk to develop uveites. Objectives The primary aim of this study is to evaluate longitudinally the effect of non-systemic therapy and of systemic immmunomodulating drugs (e.g MTX) on ANAs in JIA patients; secondary occurance of iridocyclitis was evaluated. Methods Monocentric retrospective not randomised study of 40 patients affected by oligoarticular JIA (ILAR classification) with ANA positivity at the baseline (T0, time of diagnosis). Patient of Group 1 received only intra-articular infiltrations or NSAID. Patients of Group 2 were treated with DMARDs (most of them with subcutaneous MTX 15 mg/m2/week) or MTX +biotechnlogical therapies. The assay for ANAs (I.I.F.) was assessed in all patients at T0, at T1 (12 months) and T2 (24 months). At 24 months was also recorded the occurence of uveitis during the follow up. Exclusion criteria were the ANAs negativity at T0 and other subgroups of JIA. Results Twenty-one patients (52,5%) were treated with non-systemic therapy (Group 1), and ninenteen (47,5%) with systemic immunomodulating therapy (Group 2). In Group 2 fifteen subjects were treated with MTX, one with MTX plus cyclosporine, one with only cyclosporine, two with MTX plus biotechnological agent (etarnecept and adalimumab). At T1, in Group 1 only one patient out of 20 (4,8%) became ANAs negative versus 42,1% (8/19) of patients in Group 2 (p 0.0033). At T2 the incidence of ANAs positivity did not change in Group 1 (only 1/21 ANAs negative), while 42,1% of patients treated with systemic therapies were ANA negative (p 0.006). Three patients were lost at the follow up. The two patients who received bDMARDs in addition to MTX remained ANAs-positive both in T1 and T2. At the end of follow-up period eight uveitis have occured, six in ANAs positive patients of Group 1 (6/21, 28,5%) and two in ANA negatives patients in Group 2 (2/19, 10,5%). Conclusions ANAs-positive patients treated with methotrexate seems to have higher possibility to became ANAs-negative versus patients treated with non-systemic immunomodulating therapy. It’s known that MTX might prevent onset of uveitis in JIA, as shown in our results. Demostrating a negativization of antinuclear antibodies using MTX therapy could help to add a role of this drug in the disease history of the oligoarthritis. Disclosure of Interest None declared

Background Acute rheumatic fever is a nonsuppurative sequela that occurs two to four weeks following group A beta-hemolytic Streptococcus (GABHS) pharyngitis. Despite its decline in incidence in Europe, rheumatic fever still represents a serious healthcare concern. The most common manifestations are arthritis and carditis, followed by chorea, erythema marginatum, and subcutaneous nodules. The diagnosis of ARF is clinical and requires satisfaction of revised Jones criteria as well as evidence of a recent streptococcal infection. Objectives Aim of this study was to highlight new emerging features of disease clinical presentation. Methods Data regarding patients who fulfilled the Revised Jones Criteria for acute rheumatic fever were retrospectively collected from January 1996 and July 2017. The following clinical and demographic data were obtained: patient sex, birth date, age at presentation, clinical manifestations, evolution of cardiac involvement after therapy. Results 35 patients (19 males, 16 females) were included. The mean age at diagnosis 7,9±4 years (range 2–17). Carditis was the most frequent manifestation, occurring in 31 patients (89%). Other common symptoms were fever (91%), artrhtiris (43%) or arthralgias (54%) and chorea (20%). In 6 out of 7 patients chorea occurred together with carditis. Cardiac auscultation revealed new pathologic murmurs only in 49% of cases. Echocardiography detected cardiac involvement in the absence of auscultatory findings (subclinical carditis) in 11 patients at the time of diagnosis. In 3 cases ultrasound examination became positive within 4 weeks. Throat cultures were negative in 37% of cases. Anti-streptolysin O (ASO) and anti-desoxyribonuclease B (ADB) antibodies titers did not bear correlation with the severity of cardiac involvement. Conclusions In our casistic, carditis was the most common and worrysome manifestation of ARF. Detection of cardiac involvement is still challenging and echocardiography testing should be performed even in the absence of abnormal auscultation findings. If the initial ultrasound is negative but clinical suspiciun remains high, US investigation should be repeated, given that rheumatic carditis can evolve over weeks to months. Early detection and treatment of manifestations improves outcome as in all the cases of this series. Streptococcal serology is most helpful in the diagnosis of ARF because culture or detection of the organism is usually no longer possible by the time ARF presents. The severity of clinical manifestations, particularly of carditis, does not correlate strictly with ASO and ADB titer. Sydenham chorea, which usually has a longer latent period (up to 6 months), tends to occur earlier in the disease course, presenting in the acute phase in this series. References [1] Gewitz MH, et al. Revision of the Jones Criteria for the Diagnosis of Acute Rheumatic Fever in the Era of Doppler Echocardiography A Scientific Statement From the American Heart Association. Circulation. 2015May 19;131(20):1806–18. [2] Parks T, et al. ASO titer or not? When to use streptococcal serology: a guide for clinicians. Eur J Clin Microbiol Infect Dis. 2015May;34(5):845–9. Disclosure of Interest None declared

Building on the successful experience in operating the DarkSide-50 detector, the DarkSide Collaboration is going to construct DarkSide-20k, a direct WIMP search detector using a two-phase Liquid Argon Time Projection Chamber (LAr TPC) with an active (fiducial) mass of 23 t (20 t). This paper describes a preliminary design for the experiment, in which the DarkSide-20k LAr TPC is deployed within a shield/veto with a spherical Liquid Scintillator Veto (LSV) inside a cylindrical Water Cherenkov Veto (WCV). This preliminary design provides a baseline for the experiment to achieve its physics goals, while further development work will lead to the final optimization of the detector parameters and an eventual technical design. Operation of DarkSide-50 demonstrated a major reduction in the dominant 39Ar background when using argon extracted from an underground source, before applying pulse shape analysis. Data from DarkSide-50, in combination with MC simulation and analytical modeling, shows that a rejection factor for discrimination between electron and nuclear recoils of $>3 \times 10^{9}$ is achievable. This, along with the use of the veto system and utilizing silicon photomultipliers in the LAr TPC, are the keys to unlocking the path to large LAr TPC detector masses, while maintaining an experiment in which less than $< 0.1$ events (other than $\nu$ -induced nuclear recoils) is expected to occur within the WIMP search region during the planned exposure. DarkSide-20k will have ultra-low backgrounds than can be measured in situ, giving sensitivity to WIMP-nucleon cross sections of $1.2 \times 10^{-47}$ cm2 ( $1.1 \times 10^{-46}$ cm2) for WIMPs of 1 TeV/c2 (10 TeV/c2) mass, to be achieved during a 5 yr run producing an exposure of 100 t yr free from any instrumental background.

International audience; We report on the cryogenic characterization of Red Green Blue - High Density (RGB-HD) SiPMs developed at Fondazione Bruno Kessler (FBK) as part of the DarkSide program of dark matter searches with liquid argon time projection chambers. A cryogenic setup was used to operate the SiPMs at varying temperatures and a custom data acquisition system and analysis software were used to precisely characterize the primary dark noise, the correlated noise, and the gain of the devices. We demonstrate that FBK RGB-HD SiPMs with low quenching resistance (RGB-HD-LRq) can be operated from 40 K to 300 K with gains in the range 10(5) to 10(6) and noise rates at a level of around 1 Hz/mm(2).

Summary A series of 1000 cases was selected, on the basis of a clinical andlor post-mortem diagnosis of cancer, out o f 4927 autopsies performed at the Institute of Pathologic Anatomy and Histopathology of Turin University. The comparison between clinical and post-mortem diagnoses pointed to an overall concordance with regard to the correct identification of a malignancy as the underlying cause of death of 75%; if the correct identification of type and primary site of the tumor was also taken into account, the concordance was only 56%. The rate of false-positive and false-negative diagnoses, the confirmation rate and sensitivity index of clinical diagnoses, and the error of estimate of the overall frequency of the different types of tumors were computed. Pancreas, liver and biliary tract tumors appear to be the most difficult to identify correctly during life; also lung, stomach and colorectal cancers, lymphomas and leukemias show fairly high rate of clinical errors. Breast cancer, tumors of the nervous system and colorectal cancers appear to be overnotified. These results seem to underscore the necessity of being very careful in drawing conclusions on the frequency and distribution of the different types of cancer on the basis of current mortality statistics.

Summary The lung concentration of coated and uncoated mineral fibres of more than 10 μm in length was determined by light microscopy in 57 autopsied subjects (23 out of which professionally exposed to asbestos) with pleural plaques but no other asbestos-related diseases. Comparisons were made with 57 controls matched for sex, age and smoking habits, who did not show any asbestos-associated diseases or history of previous occupational exposure. Subjects with pleural plaques had a median concentration of coated fibres consistently greater than that observed in those without. However, no substantial differences were found between the two studied groups when uncoated and total fibres were considered. The present study suggests that the factors related to the fibre coating and to the pleural plaque formation may be indirectly connected, but not necessarily restricted to the number and nature of the fibres, or to the professional or environmental conditions of exposure.