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Three-pion Bose-Einstein correlations measured in proton-proton collisions
No full textA study on the Bose-Einstein correlations for triplets of same-sign pions is presented. The analysis is performed using proton-proton collisions at a centre-of-mass energy of s = 7 TeV, recorded by the LHCb experiment, corresponding to an integrated luminosity of 1.0 fb-1. For the first time, the results are interpreted in the core-halo model. The parameters of the model are determined in regions of charged-particle multiplicity. This measurement provides insight into the nature of hadronisation in terms of coherence, being consistent with the presence of coherent emission of pions
Divergent Morphologies and Common Signaling Features of Active and Inactive Oncogenic RHOA Mutants in Yeast
No full textRHOA, a member of the Rho family of small GTPases, harbors recurrent mutations in diverse cancers, but how these mutations cause their cellular effects remains poorly understood. To investigate their cellular consequences, we expressed oncogenic RHOA variants (R5Q, G17V, C16R, and A161P) in Saccharomyces cerevisiae, substituting for the essential yeast homologue RHO1. While the E40Q variant failed to complement RHO1 deletion, other mutants supported viability and enabled phenotypic characterization. All four variants conferred myriocin resistance, suggesting activation of the membrane stress response pathway, but induced no major changes in growth or caspofungin sensitivity. Using high-dimensional image analysis, we quantified 501 morphological parameters and applied principal component analysis and linear discriminant analysis to determine distinct phenotypic profiles. Gain-of-function (C16R and A161P) and loss-of-function (R5Q and G17V) mutants formed separate morphological clusters, indicating functional divergence. Our yeast model enabled systematic dissection of the functions of RHOA mutants and highlighted the utility of morphology-based approaches to characterize context-dependent mechanisms of oncogenesis.</p
Role of Intestinal Fatty Acid Binding Protein in Diagnosing Adhesive Small Bowel Obstruction:A Pilot Study
No full textINTRODUCTION: The incidence of adhesive small bowel obstruction (ASBO) after abdominal surgery is 2.4%. Delay in surgery increases morbidity and mortality. Plasma intestinal fatty acid binding protein (I-FABP) levels indicate intestinal damage and may guide treatment. The aim of this study was to investigate whether plasma I-FABP levels may optimize selection of patients requiring surgery presenting with ASBO. METHODS: Patients with suspected ASBO underwent a contrast swallow. If bowel transit was absent after 8 h, surgery was performed. I-FABP levels were assessed at several moments. Data were analyzed by comparing groups based on bowel transit, ischemia, and positive or negative laparotomies. Furthermore, a true operative group (patients with mechanical obstruction during surgery and patients needing operative treatment who deceased due to non-operative treatment) was compared to a true non-operative group (patients with negative laparotomies and patients successfully treated with non-operative treatment). RESULTS: Median I-FABP levels were higher in patients without bowel transit (1,207 pg/mL) than in patients with bowel transit (589 pg/mL, p = 0.01). Median I-FABP levels in the negative laparotomy group (301 pg/mL) showed a trend to significance compared to the positive laparotomy group (1,177 pg/mL, p = 0.05). There was no significant difference between the true operative group (1,150 pg/mL) and the true non-operative group (664 pg/mL) or between proven ischemia (975 pg/mL) and no ischemia (921 pg/mL). CONCLUSION: I-FABP might help identify ASBO patients in whom surgery can be postponed
Psychometric Evaluation of the Borderline Personality Disorder Checklist
No full textBACKGROUND: Borderline Personality Disorder (BPD) is a severe and disabling condition. The Borderline Personality Disorder Checklist (BPDCL) was designed to specifically assess the subjective burden of a patient due to BPD symptoms. Various translations have been developed, but an assessment of the psychometric properties of these translations is needed. The aim was to examine the psychometric qualities of the BPDCL across different languages (i.e., Italian, Dutch, German, Spanish, English, and Greek). METHODS: Secondary data was used by reaching out to various researchers, who administered the BPDCL in previous studies. Five studies (N = 3199) conducted in Spain, Germany, Italy, the Netherlands, Australia, England, and Greece, were included in the current data set. The BPDCL was administered to BPD patients (N = 1131), Axis I disorder patients (N = 57), patients with other personality disorders (N = 225), and healthy controls (N = 1786). Item analyses and analyses assessing the known-groups and convergent validity were performed to investigate the psychometric properties of the checklist. RESULTS: Each version of the BPDCL, differing in language, demonstrated high-reliability coefficients (Cronbach's Alpha ranged from 0.93 to 0.96 and was 0.96 for the entire sample). The correlations between the BPDCL and other instruments, used in the studies, were weak to strong. Correlations greater than 0.55 were observed between the BPDCL and the scales BPDSI, SCL-90 and the BSI. In addition, the BPDCL seems to differentiate well between diagnostic groups. BPD patients scored the highest, followed by patients with other personality disorders, who in turn scored higher than Axis I disorder patients and healthy controls. CONCLUSIONS: In general, the BPDCL possesses good psychometric properties and seems to be an adequate self-report instrument to measure the subjective burden of BPD patients
The Cost of Anonymity in the Sharing Economy:Consumers Distrust and Avoid Sellers Without Profile Photos
No full textSharing economy platforms, such as Airbnb, encourage sellers to display profile photos and other personal information to increase consumer trust and engagement. However, research has shown that consumers rely on this information to discriminate against sellers with certain characteristics (e.g., ethnic minorities). Some sharing economy sellers may therefore choose not to display a profile photo because they wish to conceal their appearance or social identity to prevent discrimination or other unfavorable treatment by consumers or because of general privacy concerns. In four preregistered studies with samples from the United States, United Kingdom, and the Netherlands, we examined the consequences of withholding profile profiles. We tested how the presence (vs. absence) of personal photos affects consumer trust and preferences for different sellers. Three experimental studies (total = 380) suggest that consumers distrust and avoid hosts without a profile photo. In Study 4, we analyzed 461 ride-sharing listings and found that drivers with a profile photo charge higher prices for otherwise equivalent rides. In sum, our results suggest that sharing economy sellers face a tradeoff between anonymity and earning opportunities
Neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy in resectable and borderline resectable pancreatic cancer (PREOPANC-2):a multicentre, open-label, phase 3 randomised trial
No full textBACKGROUND: The PREOPANC-2 trial aimed to evaluate whether neoadjuvant FOLFIRINOX improved overall survival compared with neoadjuvant gemcitabine-based chemoradiotherapy followed by adjuvant gemcitabine in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC). METHODS: In this investigator-initiated, open-label, nationwide, phase 3 randomised trial, patients aged 18 years or older with resectable or borderline resectable PDAC and a WHO performance status of 0 or 1 were enrolled across 19 Dutch centres. Patients in the FOLFIRINOX (FFX) group received FOLFIRINOX (85 mg/m intravenous oxaliplatin, 180 mg/m intravenous irinotecan, 400 mg/m intravenous leucovorin, followed by a 400 mg/m intravenous fluorouracil bolus and then continuous infusion at 2400 mg/m intravenously over 46 h every 14 days for eight cycles) followed by surgery without adjuvant treatment. Patients in the chemoradiotherapy (CRT) group received three cycles of neoadjuvant gemcitabine (1000 mg/m intravenously on days 1, 8, and 15 of each 28-day cycle and on days 1 and 8 only for cycles one and three) combined with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle only, followed by surgery and four cycles of adjuvant gemcitabine. Randomisation (1:1) was done using a minimisation technique and stratified by resectability status (resectable vs borderline resectable disease) and centre. The primary endpoint was overall survival in the modified intention-to-treat population, after excluding ineligible patients. Data on race and ethnicity were not collected. This trial is registered with EudraCT (2017-002036-17) and is complete. FINDINGS: From June 5, 2018, to Jan 28, 2021, 375 patients were randomly assigned to the FFX group (n=188) or the CRT group (n=187). Six patients (three per group) were excluded due to ineligibility (n=4) or immediate withdrawal of informed consent after randomisation (n=2). 208 (56%) of 369 patients were male and 161 (44%) were female. After a median follow-up of 42·3 months (IQR 35·7-48·7), median overall survival was 21·9 months (95% CI 17·7-27·0) in the FFX group versus 21·3 months (16·8-25·5) in the CRT group (HR 0·88 [95% CI 0·69-1·13], p=0·32). The most common grade 3-4 adverse events were neutropenia (43 [25%] of 175 in the FFX group vs 38 [22%] of 176 in the CRT group), diarrhoea (41 [23%] vs two [1%]), and leukopenia (14 [8%] vs 26 [15%]). Serious adverse events occurred in 85 (49%) patients in the FFX group compared with 75 (43%) in the CRT group (p=0·26). Adverse events of grades 3 or worse occurred in 117 (67%) patients in the FFX group versus 106 (60%) patients in the CRT group (p=0·20). Treatment-related deaths occurred in two (1%) patients in the FFX group (multi-organ failure and intestinal mucositis) and one (1%) patient in the CRT group (upper gastrointestinal haemorrhage). INTERPRETATION: This randomised trial did not show a difference in overall survival between neoadjuvant FOLFIRINOX and neoadjuvant gemcitabine-based chemoradiotherapy in patients with resectable or borderline resectable PDAC. Both neoadjuvant treatment regimens may be considered in these patients. FUNDING: Dutch Cancer Society and ZonMw
Development and validation of a Disease Activity index for PSoriatic Arthritis based on 44 joints (DAPSA44)
No full textOBJECTIVES: This study aims to develop a modified Disease Activity index for PSoriatic Arthritis (DAPSA) score using the 44-joint count instead of the 66 swollen/68 tender joint counts (SJC/TJC) in patients with spondyloarthritis (SpA) (axial SpA [axSpA], peripheral SpA [pSpA], and psoriatic arthritis [PsA]) and evaluate its construct validity. METHODS: Patients with axSpA, pSpA, and PsA included in the Assessment of SpondyloArthritis international Society-PerSpA (PERipheral involvement in SpondyloArthritis) study were randomly allocated 1:2 stratified for diagnosis and country into a derivation and validation cohort. For all patients, the 66SJC/68TJC were available, from which the SJC44/TJC44 were extracted. The derivation cohort was used to calculate the conversion factors for SJC66/TJC68 into SJC44/TJC44 to obtain the DAPSA44 using mixed-effects linear regression models. The validation cohort assessed the DAPSA44 construct validity through the agreement between continuous original-DAPSA/DAPSA44 (intraclass correlation coefficient [ICC]) and DAPSA disease activity states (weighted-kappa), Bland-Altman plot, Spearman correlations between original-DAPSA/DAPSA44 and external constructs, and discrimination between known groups (standardised mean differences [SMDs]) after stratifying patients into active/inactive based on a combination of patient global assessment (=5/<5) and SJC (=1/0 or =2/<2). RESULTS: A total of 4121 patients (65% axSpA, 10% pSpA, and 25% PsA) were included. Conversion factors from the derivation cohort (n = 1364) for TJC and SJC were 1.30 and 1.34, respectively. The validation cohort (n = 2757) analyses showed almost-perfect agreement between original-DAPSA and DAPSA44 (ICC 0.98, kappa 0.95). Spearman correlation coefficients between DAPSA44 and external constructs fell within the predefined 0.3-wide range of corresponding original-DAPSA coefficients. DAPSA44 demonstrated excellent discriminatory ability (SMD > 0.8) across all scenarios of active/inactive disease. CONCLUSIONS: These findings support the use of DAPSA44 as a comparable tool to the original DAPSA for assessing disease activity due to peripheral arthritis in SpA, especially in situations where only a reduced joint count is available
The independent and combined effects of smoking and chronic obstructive pulmonary disease on body mass index trajectories
No full textLow body mass index (BMI) is a common feature of severe chronic obstructive pulmonary disease (COPD) but in the general population, cigarette smoking is also associated with low body weight. Many people with COPD remain smokers after diagnosis, and it is unclear whether low BMI is because of the disease itself or its most common risk factor. We aim to assess the independent and combined effects of smoking and COPD on BMI trajectories. 27,651 patients without COPD and 25,990 with COPD from The Health Improvement Network (2005-2019) were grouped into: never-smokers, former smokers, sustained quitters, intermittent smokers, and continuous smokers (ten total COPD-smoking status groups). BMI trajectories over 10-year time horizon were modeled by these status groups using multivariable mixed-effect models adjusted for age (in continuous years), sex, Townsend score (a measure of material deprivation), alcohol consumption (yes/no), exacerbation history (yes/no, only for COPD patients) and any history of asthma, cancer, chronic kidney disease, diabetes, or cardiovascular disease (yes/no). Individuals with COPD who smoked at baseline (intermittent, sustained quitter, or continuous smokers) had a lower initial BMI (27.1 kg/m² [26.9-27.3]; 26.6 [26.4-26.9]; 26.2 [26.0-26.4], respectively) than non-COPD controls in the same smoking categories (28.0 [26.6-28.2]; 27.6 [27.2-27.9]; 26.7 [26.4-26.9]). Current smokers had lower initial BMIs than never and former smokers, regardless of COPD status. In individuals with COPD, compared to former smokers, continuous smokers lost weight faster (-0.071 kg/m²/year [-0.097 to -0.045]; p < 0.001), while quitters gained weight (0.266 [0.233 to 0.298]; p < 0.001). Non-COPD controls showed similar but less pronounced patterns when continuous smokers and quitters (-0.059 [-0.090 to -0.028] and 0.213 [0.173 to 0.254], respectively; both p < 0.001) were compared to former smokers. Those with a baseline BMI of < 30 also showed a decrease in longitudinal BMI, especially among COPD patients. COPD patients had lower baseline BMI than controls, but BMI trajectories were similar between groups, with continuous smokers losing weight faster and quitters gaining weight. These findings suggest that smoking behaviour significantly influences weight loss in COPD, emphasizing its importance in clinical evaluations and nutritional support consultations
