Bayesian clustering of multiple zero-inflated outcomes

Several applications involving counts present a large proportion of zeros (excess-of-zeros data). A popular model for such data is the hurdle model, which explicitly models the probability of a zero count, while assuming a sampling distribution on the positive integers. We consider data from multiple count processes. In this context, it is of interest to study the patterns of counts and cluster the subjects accordingly. We introduce a novel Bayesian approach to cluster multiple, possibly related, zero-inflated processes. We propose a joint model for zero-inflated counts, specifying a hurdle model for each process with a shifted Negative Binomial sampling distribution. Conditionally on the model parameters, the different processes are assumed independent, leading to a substantial reduction in the number of parameters as compared with traditional multivariate approaches. The subject-specific probabilities of zero-inflation and the parameters of the sampling distribution are flexibly modelled via an enriched finite mixture with random number of components. This induces a two-level clustering of the subjects based on the zero/non-zero patterns (outer clustering) and on the sampling distribution (inner clustering). Posterior inference is performed through tailored Markov chain Monte Carlo schemes. We demonstrate the proposed approach on an application involving the use of the messaging service WhatsApp. This article is part of the theme issue 'Bayesian inference: challenges, perspectives, and prospects'

INTEGRIN ALPHA2BBETA3 GENE POLYMORPHISM AND THE MICROVASCULAR SYSTEM IN SCLERODERMA

Background: Immunosuppression induced by drugs administrated to patients with autoimmune diseases can affect the course of HBV infection, both in terms of reactivation and precipitation of a pre-existing chronic hepatitis (1, 2). Anti TNF-α drugs have been recently reported to be safe in patients with potentially occult hepatitis B (3). Objectives: At the best of our knowledge, the role of traditional DMARDs in altering the course of HBV infection has not yet been assessed. In our study we evaluated this role. Methods: 148 non HCV-infected patients with autoimmune rheumatic disease (i.e. Rheumatoid arthritis, 78; psoriatic arthritis, 36; systemic vasculitides, 14; Sjogren syndrome and UCTD, 11; systemic lupus erythematosus, 9) were assessed for HBV markers at baseline and followed for 5-31 months (median 21 months). They were administered the following DMARDS: methotrexate (MTX)74; azatioprine 30; cyclosporine A (CyA) 16; leflunomide 12; mofetil mycophenolate 5; middle or high steroid dose 8; cyclophosphamide 1; MTX+CyA 2. Patients undergoing low-risk treatments(1), including hydroxychloroquine, sulfasalazine and low dose steroids were excluded. Results: At baseline 9 (6%) were HBsAg positive; 22 (15%) were HBsAb and HBcAb positive; 11 (7.4%) were HBcAb positive (without HBsAg or HBsAb); 5 (3.4%) were HBsAb positive (without HBcAb) because of a previous vaccination. During treatment, abnormal liver function test (LFT) were detected in 42 patients: 29(52.7%) were drug-related; 9 (16.4%) were due to a coexisting autoimmune liver dysfunction; 1 (1.8) was due to a steatosis; 3 (5.5%) were due to a HBV infection reactivation: 2 among the 9 HBsAg positive patients (22%), and 1 among the 33 potential occult HBV carriers (3%). Conclusions: Spontaneous flares in chronic hepatitis B have been reported (4). Zacharakis et al (5) found 4 cases (2%) of reactivation among 195 HBsAg positive inactive carriers. In our cohort 3 cases of HBV reactivation occurred (2 out of 9 HBsAg positive carriers, and 1 out of 33 potential occult carriers). National and International guidelines suggest a careful assessment of HBV infection in rheumatic patients undergoing immunosuppressive therapies. Our data support the safety of such drugs pointing out a low prevalence (3%) of HBV reactivation in potentially occult carriers

Field validation of innovative feeds targeting gut integrity and feces quality in rainbow trout Oncorhynchus mykiss

Solid waste production from rainbow trout (Oncorhynchus mykiss) farms is known to increase in wintertime, possibly as a result of reduced dry matter digestibility at low temperatures. At the same time the quality of the feces changes, in that their stability in water seems to decrease and they fall apart in water as whitish flakes. Gut histology performed on trout sampled in wintertime highlighted some pathohistological changes, which may be related to the above mentioned effects. A specifically formulated diet targeting enhanced digestibility and gut protection has been proved in lab scale to significantly reduce volume of feces produced under simulated winter conditions. Following further refinement of the formulation, a field trial was set up with 57000 rainbow trout (average initial weight 150-200 g) fed in duplicate either a control (CD) or an experimental (Defender-GE) diet. The trial was carried out under natural winter conditions in Northern Italy (average temperature 6and lasted 80 days. The fish fed Defender-GE showed higher growth rate (+14% when expressed as Thermal Growth Coefficient) and lower Feed Conversion Ratio (-24%) compared to the control ones. As a result, the feeding cost per kg biomass gain decreased by 12% for the units fed Defender-GE. Hystological analyses confirmed that this latter diet exerted a protective effect towards the intestinal epithelium, possibly enhancing lipid and therefore energy absorption. Feces quality dramatically improved in fish fed Defender-GE, with higher stability of fecal pellets,as such in turns reducing suspended solids in water. A specifically formulated diet may therefore be a tool to enhance gut integrity and improve feces quality in rainbow trout under winter conditions, while supporting growth rates and reducing feeding costs

Reduced type I collagen gene expression by skin fibroblasts of patients with systemic sclerosis after one treatment course with rituximab

Objective. There is evidence that B lymphocytes play a role in the pathogenesis of systemic sclerosis (scleroderma). Stimulatory autoantibodies targeting and activating normal human fibroblasts in vitro have been demonstrated in sera from scleroderma patients. Rituximab is a monoclonal antibody which selectively targets and depletes CD20+ B lymphocytes. We investigated the biological effects of rituximab in six patients affected by scleroderma with severe skin involvement. Methods. Six patients with severe skin fibrosis, unresponsive to immunosuppressive treatment, were treated with 375 mg/m2 per week of intravenous rituximab for a total of four doses. Serum stimulatory autoantibodies to the PDGF receptor were detected. Fibroblast activation was evaluated in fibroblasts grown from skin biopsies performed at baseline and at months 3 and 6 post-treatment. The modified Rodnan's skin score, health assessment questionnaire (HAQ) and visual analogic scale (VAS) for global wellness and B lymphocyte count were performed monthly. Results. A significant reduction of anti- PDGF receptor autoantibodies was observed in the serum of all patients 3 months after treatment. Fibroblasts showed a significant downregulation of type I collagen gene expression and of the intracellular signalling triggered by anti-PDGFR autoantibodies. A decrease of the skin score and an improvement of disability indexes matched with the in vitro results. A single course of rituximab reduced scleroderma fibroblast activation in vitro and the serum levels of anti-PDGFR stimulatory autoantibodies. Conclusion. These data provide further evidence of B-cell involvement in the pathogenesis of scleroderma. Targeting B cells may be a promising treatment for scleroderma patients, and controlled clinical trials are warranted. \ua9 Clinical and Experimental Rheumatology 2015

Alveolar haemorrhage in ANCA-associated vasculitis: Long-term outcome and mortality predictors

Introduction: Alveolar haemorrhage (AH) is considered an important cause of morbidity and early mortality in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV). Objectives: The aim of this study was to identify predictors of outcome in patients with AH-AAV and to evaluate outcome and causes of death in this subset. Materials and methods: A multicenter retrospective study was conducted in 29 Italian Centers. Clinicians were asked to recruit all patients diagnosed with AAV-associated AH during the last 10 years, from 2007 to 2016. Univariate and multivariable analysis were performed. Results: One-hundred and six patients were included (median age at onset of 55 years [IQR 42\u201367]). The majority were ANCA-positive (PR3 57.1%, MPO 33.7%) and 72.6% had also renal involvement. At presentation, anaemia was shown in 97 (92.4%) patients, hemoptysis in 54 (51.9%), respiratory failure in 68 (66.7%), of whom 48 (70.6%), requiring respiratory support. At the end of the 37 months [IQR 13\u201377] follow-up, 19/106 (17.9%) patients were dead. The main causes of death were active disease and infections. By stepwise regression analysis, age >65 years (HR 3.66 [95% CI 1.4\u20139.51], p = 0.008) and the need for respiratory support (HR 4.58 [95% CI 1.51\u201313.87], p = 0.007) at AH onset were confirmed to be predictive of mortality. Conclusions: Predictors of outcome in AAV-AH were determined. Factors related to the patient's performance status and the severity of the lung involvement strongly influenced the outcome. Balancing harms and benefits for the individual patient in induction and maintenance treatment strategies is crucial