RF Design of the X-band Linac for the EuPRAXIA@SPARC_LAB Project

We illustrate the RF design of the X-band linac for the upgrade of the SPARC_LAB facility at INFN-LNF (EuPRAXIA@SPARC_LAB). The structures are travelling wave (TW) cavities, working on the 2π/3 mode, fed by klystrons with pulse compressor systems. The tapering of the cells along the structure and the cell profiles have been optimized to maximize the effective shunt impedance keeping under control the maximum value of the modified Poynting vector, while the couplers have been designed to have a symmetric feeding and a reduced pulsed heating. In the paper we also present the RF power distribution layout of the accelerating module and a preliminary mechanical design

Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma

Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE

Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of three new genome-wide association studies (GWAS) and one prior scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of nine promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; $P=2.33x10^{-21}$), rs2523607 at 6p21.33 (HLA-B; $2.40x10^{-10}$), rs79480871 at 2p23.3 (NCOA1; $P=4.23x10^{-8}$), and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; $P=9.98x10^{-13}$ and $P=3.63x10^{-11}$, respectively). These data provide substantial new evidence for genetic susceptibility to this B-cell malignancy, and point towards pathways involved in immune recognition and immune function in the pathogenesis of DLBCL

Predictors of emergency department referral in patients using out-of-hours primary care services

Out of hours (OOH) doctors could manage many cases limiting the inappropriate accesses to ED. However the possible determinants of referral to ED by OOH doctors are poorly studied. We aimed to characterize patients referred from the OOH to ED service in order to explore the gate-keeping role of OOH service for hospital emergency care and to facilitate future research in improving its cost-effectiveness. A retrospective study was made through data collection of 5217 contacts in a local OOH service in the North-East of Italy (from 10/01/2012 to 03/31/2013). Only 8.7% (=454 people) of the total contacts were referred to ED. In the multivariate analysis, the significant predictors of being sent to ED were: age; residence in nursing home (odds ratios (OR)=2.00, 95%CI: 1.30-3.10); being visited by a OOH physician (OR=2.64, 95%CI: 2.09-3.34). Taking infections as reference, cardiovascular diseases (OR=18.31, 95%CI: 12.01-27.90), traumas (OR=8.75, 95%CI: 5.36-14.26) and gastrointestinal conditions (OR=7.69, 95%CI: 4.70-11.91) increased the probability to be referred to ED. OOH service addresses several common medical conditions in community-dwelling and in nursing home context, supporting its filtering function for the ED access. The main reasons of ED referral, as shown by our study, could be a crucial aspect in general population education in order to avoid the overcrowding of the ED

Combination of mucosa-exposure device and computer-aided detection for Adenoma Detection during Colonoscopy: a randomized trial

Background & aims: Both Computer-aided detection (CADe)- assisted and Endocuff-assisted colonoscopy have shown to increase adenoma detection. We investigated the performance of the combination of the two tools compared to CADe-assisted colonoscopy alone to detect colorectal neoplasias during colonoscopy in a multicenter randomized trial. Methods: Men and women undergoing colonoscopy for CRC screening, polyp surveillance, or clincial indications at 6 centers in Italy and Switzerland were enrolled. Patients were assigned (1:1) to colonoscopy with the combinations of CADe (GI-Genius, Medtronic) and a mucosal exposure device (Endocuff Vision -ECV-, Olympus) or to CADe-assisted colonoscopy alone (control group). All detected lesions were removed and sent to histopathology for diagnosis. The primary outcome was adenoma detection rate (ADR, the percentage of patients with at least 1 histologically proven adenoma or carcinoma). Secondary outcomes were adenomas detected per colonoscopy, advanced adenomas and serrated lesions detection rate, the rate of unnecessary polypectomies (polyp resection without histologically proven adenomas), and withdrawal time. Results: From July 1, 2021 to May 31, 2022, 1316 subjects were randomized and eligible for analysis; 660 to the ECV group, 656 to control group). The ADR was significantly higher in the ECV group (49.6%) than in the control group (44.0%) (relative risk [RR], 1.12; 95% confidence interval [CI], 1.00-1.26; p = 0.04). Adenomas detected per colonoscopy were significantly higher in the ECV group (mean, 0.94+0.54) than in the control group (0.74+0.21) (incidence rate ratio, 1.26; 95% CI: 1.04-1.54; p: 0.02). The two groups did not differ in term of detection of advanced adenomas and serrated lesions. There was no significant difference between groups in withdrawal time (9.01±2.48 seconds for the ECV group vs 8.96 ±2.24 for controls; P = 0.69) or proportion of subjects undergoing unnecessary polypectomies (RR: 0.89; 95% CI: 0.69-1.14. p: 0.38). Conclusions: The combination of CADe and EndocuffVision during colonoscopy increases ADR and adenomas detected per colonoscopy without increasing withdrawal time compared to CADe alone. Clinicaltrials: gov no: NCT04676308

RF Design of the X-band Linac for the EuPRAXIA@SPARC_LAB Project

We illustrate the RF design of the X-band linac for the upgrade of the SPARC_LAB facility at INFN-LNF (EuPRAXIA@SPARC_LAB). The structures are travelling wave (TW) cavities, working on the 2π/3 mode, fed by klystrons with pulse compressor systems. The tapering of the cells along the structure and the cell profiles have been optimized to maximize the effective shunt impedance keeping under control the maximum value of the modified Poynting vector, while the couplers have been designed to have a symmetric feeding and a reduced pulsed heating. In the paper we also present the RF power distribution layout of the accelerating module and a preliminary mechanical design

Association between autism spectrum disorder and inflammatory bowel disease: a systematic review and meta-analysis

Children with autism spectrum disorder (ASD) are frequently diagnosed with co-occurring medical conditions including inflammatory bowel disease (IBD). To investigate the association, we conducted a systematic review registered in PROSPERO (ID:CRD42021236263) with a random-effects meta-analysis. We searched PubMed, Embase, and PsycInfo (last search on January 25, 2021), and manually searched relevant publications. We included observational studies measuring the association between ASD and IBD. The primary outcome was the association (odds ratio, OR) between ASD and later development of IBD. Sensitivity analyses were conducted by quality, confounding adjustment, and study design. We performed meta-regression analyses and assessed heterogeneity, publication bias, and quality of studies with the Newcastle-Ottawa Scale. Overall, we included six studies consisting of eight datasets, including over 11 million participants. We found that ASD was significantly associated with subsequent incident IBD (any IBD, OR = 1.66, 95% confidence interval[CI] = 1.25–2.21, p < 0.001; ulcerative colitis, OR = 1.91, 95%CI = 1.41–2.6, p < 0.001; Crohn's disease, OR = 1.47, 95%CI = 1.15–1.88, p = 0.002). ASD and IBD were also associated regardless of temporal sequence of diagnosis (any IBD, OR = 1.57, 95%CI = 1.28–1.93, p < 0.001; ulcerative colitis, OR = 1.7, 95%CI = 1.36–2.12, p < 0.001; Crohn's disease, OR = 1.37, 95%CI = 1.12–1.69, p = 0.003). Sensitivity analyses confirmed the findings of the main analysis. Meta-regression did not identify any significant moderators. Publication bias was not detected. Quality was high in four datasets and medium in four. In conclusion, our findings highlight the need to screen for IBD in individuals with ASD, and future research should identify who, among those with ASD, has the highest risk of IBD, and elucidate the shared biological mechanisms between ASD and IBD

Artificial intelligence and colonoscopy experience: lessons from two randomised trials

BACKGROUND AND AIMS: Artificial intelligence has been shown to increase adenoma detection rate (ADR) as the main surrogate outcome parameter of colonoscopy quality. To which extent this effect may be related to physician experience is not known. We performed a randomised trial with colonoscopists in their qualification period (AID-2) and compared these data with a previously published randomised trial in expert endoscopists (AID-1). METHODS: In this prospective, randomised controlled non-inferiority trial (AID-2), 10 non-expert endoscopists (<2000 colonoscopies) performed screening/surveillance/diagnostic colonoscopies in consecutive 40-80 year-old subjects using high-definition colonoscopy with or without a real-time deep-learning computer-aided detection (CADe) (GI Genius, Medtronic). The primary outcome was ADR in both groups with histology of resected lesions as reference. In a post-hoc analysis, data from this randomised controlled trial (RCT) were compared with data from the previous AID-1 RCT involving six experienced endoscopists in an otherwise similar setting. RESULTS: In 660 patients (62.3±10 years; men/women: 330/330) with equal distribution of study parameters, overall ADR was higher in the CADe than in the control group (53.3% vs 44.5%; relative risk (RR): 1.22; 95% CI: 1.04 to 1.40; p<0.01 for non-inferiority and p=0.02 for superiority). Similar increases were seen in adenoma numbers per colonoscopy and in small and distal lesions. No differences were observed with regards to detection of non-neoplastic lesions. When pooling these data with those from the AID-1 study, use of CADe (RR 1.29; 95% CI: 1.16 to 1.42) and colonoscopy indication, but not the level of examiner experience (RR 1.02; 95% CI: 0.89 to 1.16) were associated with ADR differences in a multivariate analysis. CONCLUSIONS: In less experienced examiners, CADe assistance during colonoscopy increased ADR and a number of related polyp parameters as compared with the control group. Experience appears to play a minor role as determining factor for ADR. TRIAL REGISTRATION NUMBER: NCT:04260321