COMBINATIONAL MIXTURES OF MULTIPARAMETER DISTRIBUTIONS

We introduce combinatorial mixtures - a flexible class of models for inference on mixture distributions whose component have multidimensional parameters. The key idea is to allow each element of the component-specific parameter vectors to be shared by a subset of other components. This approach allows for mixtures that range from very flexible to very parsimonious, and unifies inference on component-specific parameters with inference on the number of components. We develop Bayesian inference and computation approaches for this class of distributions, and illustrate them in an application. This work was originally motivated by the analysis of cancer subtypes: in terms of biological measures of interest, subtypes may be characterized by differences in location, scale, correlations or any of the combinations. We illustrate our approach using data on molecular subtypes of lung cancer

Olive Oil and Nuts in Rheumatoid Arthritis Disease Activity

Few observational studies investigated the relationship between single food groups and disease activity in rheumatoid arthritis (RA). Within a recent Italian cross-sectional study (365 patients, median age: 58.46 years, 78.63% females), we focused on two food groups, olive oil and nuts, representing vegetable sources of fatty acids. Disease activity was measured with Disease Activity Score on 28 joints based on C-reactive protein (DAS28-CRP) and the Simplified Disease Activity Index (SDAI). Robust linear and logistic regression models included tertile-based consumption categories of each food group and several confounders. Stratified analyses were performed by disease severity or duration. Higher consumption of both food groups exerted a favorable effect on disease activity, significant only for olive oil (Beta: -0.33, p-value: 0.03) in the linear regression on the overall sample. This favorable effect was stronger in the more severe or long-standing forms of RA (p-value for heterogeneity <0.05, especially for disease severity). Significant ORs were as low as ~0.30 for both food groups, strata (i.e., more severe and long-standing RA), and disease activity measures. Mean DAS28-CRP significantly decreased by ~0.70 for olive oil and ~0.55 for nuts in the two strata; mean SDAI significantly decreased by 3.30 or more for olive oil in the two strata. Globally, the beta coefficients doubled, and the ORs halved (in absolute values) for both food groups, reaching significance in 12 of the 16 available models fitted to the more severe or long-standing RA strata. More compromised forms of RA may benefit from increasing consumption of olive oil, olives, and nuts

CAP2 dimerization regulates cofilin in synaptic plasticity and Alzheimer's disease

Abstract Regulation of actin cytoskeleton dynamics in dendritic spines is crucial for learning and memory formation. Hence, defects in the actin cytoskeleton pathways are a biological trait of several brain diseases, including Alzheimer's Disease. Here, we describe a novel synaptic mechanism governed by the cyclase-associated protein 2 (CAP2), which is required for structural plasticity phenomena and completely disrupted in Alzheimer's Disease. We report that the formation of CAP2 dimers through its Cys32 is important for CAP2 binding to cofilin and for actin turnover. The Cys32-dependent CAP2 homodimerization and association to cofilin are triggered by long-term potentiation and are required for long-term potentiation-induced cofilin translocation into spines, spine remodelling and the potentiation of synaptic transmission. This mechanism is specifically affected in the hippocampus, but not in the superior frontal gyrus, of both Alzheimer's Disease patients and APP/PS1 mice, where CAP2 is down-regulated and CAP2 dimer synaptic levels are reduced. Notably, CAP2 levels in the cerebrospinal fluid are significantly increased in Alzheimer's Disease patients but not in subjects affected by frontotemporal dementia. In Alzheimer's Disease hippocampi, cofilin association to CAP2 dimer/monomer is altered and cofilin is aberrantly localized in spines. Taken together, these results provide novel insights into structural plasticity mechanisms that are defective in Alzheimer's Disease

Machine learning in clinical and epidemiological research: isn't it time for biostatisticians to work on it?

In recent years, there has been a widespread cross-fertilization between Medical Statistics and Machine Learning (ML) techniques

Selection of modalities, prescription, and technical issues in children on peritoneal dialysis

Peritoneal dialysis (PD) is widely employed as a dialytic therapy for uraemic children, especially in its automated form (APD), that is associated with less burden of care on patient and family than continuous ambulatory PD. Since APD offers a wide range of treatment options, based on intermittent and continuous regimens, prescription can be individualized according to patient’s age, body size, residual renal function, nutritional intake, and growth-related metabolic needs. Transport capacity of the peritoneal membrane of each individual patient should be assessed, and regularly monitored, by means of standardized peritoneal function tests validated in pediatric patients. To ensure maximum recruitment of peritoneal exchange area, fill volume should be scaled to body surface area and adapted to each patient, according to clinical tolerance and intraperitoneal pressure. PD solutions should be employed according to their biocompatibility and potential ultrafiltration capacity; new pH-neutral, glucose-free solutions can be used in an integrated way in separate dwells, or by appropriately mixing during the same dialytic session. Kinetic modelling software programs may help in the tailoring of PD prescription to individual patients’ characteristics and needs. Owing to advances in the technology of new APD machines, greater programming flexibility, memorized delivery control, and tele-dialysis are currently possible

Folate intake and the risk of oral cavity and pharyngeal cancer: A pooled analysis within the International Head and Neck Cancer Epidemiology Consortium: Folate Intake and the Risk of OPC

There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPC), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. This study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium

Natural vitamin C intake and the risk of head and neck cancer: A pooled analysis in the International Head and Neck Cancer Epidemiology Consortium: Vitamin C and head and neck cancer

Evidence of associations between single nutrients and head and neck cancer (HNC) is still more limited and less consistent than that for fruit and vegetables. However, clarification of the protective mechanisms of fruit and vegetables is important to our understanding of HNC etiology

Estimating and explaining the effect of education and income on head and neck cancer risk : INHANCE consortium pooled analysis of 31 case-control studies from 27 countries

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels