Regularized brain reading with shrinkage and smoothing

Functional neuroimaging measures how the brain responds to complex stimuli. However, sample sizes are modest, noise is substantial, and stimuli are high dimensional. Hence, direct estimates are inherently imprecise and call for regularization. We compare a suite of approaches which regularize via shrinkage: ridge regression, the elastic net (a generalization of ridge regression and the lasso), and a hierarchical Bayesian model based on small area estimation (SAE). We contrast regularization with spatial smoothing and combinations of smoothing and shrinkage. All methods are tested on functional magnetic resonance imaging (fMRI) data from multiple subjects participating in two different experiments related to reading, for both predicting neural response to stimuli and decoding stimuli from responses. Interestingly, when the regularization parameters are chosen by cross-validation independently for every voxel, low/high regularization is chosen in voxels where the classification accuracy is high/low, indicating that the regularization intensity is a good tool for identification of relevant voxels for the cognitive task. Surprisingly, all the regularization methods work about equally well, suggesting that beating basic smoothing and shrinkage will take not only clever methods, but also careful modeling.Comment: Published at http://dx.doi.org/10.1214/15-AOAS837 in the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Hawkes process as a model of social interactions: a view on video dynamics

We study by computer simulation the "Hawkes process" that was proposed in a recent paper by Crane and Sornette (Proc. Nat. Acad. Sci. USA 105, 15649 (2008)) as a plausible model for the dynamics of YouTube video viewing numbers. We test the claims made there that robust identification is possible for classes of dynamic response following activity bursts. Our simulated timeseries for the Hawkes process indeed fall into the different categories predicted by Crane and Sornette. However the Hawkes process gives a much narrower spread of decay exponents than the YouTube data, suggesting limits to the universality of the Hawkes-based analysis.Comment: Added errors to parameter estimates and further description. IOP style, 13 pages, 5 figure

Study of rare gases in geothermal waters from Herculane area, Romania

In the south-western part of Romania there is a long and deep fissure following the Cerna river canyon as well as many transversal fissures, especially placed in the region of Herculane Spa. The geothermal water sources (springs and drillings), always accompanied by large amounts of gases, are located where these fissures cross. The presence of granite rocks at the surface is another remarkable characteristic of this area. Nitrogen and methane are the main components of emanated gases, and high helium and radon concentrations were also found. The composition of the gases was determined by using a Dempster mass spectrometer. The radon content from these gases and the rate of radon exhalation from the ground were determined by gamma spectrometry method. The argon isotopes were analyzed by means of a quadrupole mass spectrometer (AMP-4). In the vicinity of transversal fissures, the radon exhalation rates present higher values from all measurements in this area. The ratio 4HeO20NeD400 is a very good indicator of the fact that these gases are not contaminated with atmospheric air and therefore the gases come from depth. The 4HeO40Ar and 40ArO36Ar ratios suggest that the helium in these sources may have a non-negligible part of primordial helium arising from the earth mantle

Multistep, sequential control of the trafficking and function of the multiple sulfatase deficiency gene product, SUMF1 by PDI, ERGIC-53 and ERp44.

Sulfatase modifying factor 1 (SUMF1) encodes for the formylglicine generating enzyme, which activates sulfatases by modifying a key cysteine residue within their catalytic domains. SUMF1 is mutated in patients affected by multiple sulfatase deficiency, a rare recessive disorder in which all sulfatase activities are impaired. Despite the absence of canonical retention/retrieval signals, SUMF1 is largely retained in the endoplasmic reticulum (ER), where it exerts its enzymatic activity on nascent sulfatases. Part of SUMF1 is secreted and paracrinally taken up by distant cells. Here we show that SUMF1 interacts with protein disulfide isomerase (PDI) and ERp44, two thioredoxin family members residing in the early secretory pathway, and with ERGIC-53, a lectin that shuttles between the ER and the Golgi. Functional assays reveal that these interactions are crucial for controlling SUMF1 traffic and function. PDI couples SUMF1 retention and activation in the ER. ERGIC-53 and ERp44 act downstream, favoring SUMF1 export from and retrieval to the ER, respectively. Silencing ERGIC-53 causes proteasomal degradation of SUMF1, while down-regulating ERp44 promotes its secretion. When over-expressed, each of three interactors favors intracellular accumulation. Our results reveal a multistep control of SUMF1 trafficking, with sequential interactions dynamically determining ER localization, activity and secretion

Advanced Glycation End Products are Increased in the Skin and Blood of Patients with Severe Psoriasis

Psoriasis is frequently associated with metabolic comorbidities. Advanced glycation end products (AGEs) are highly oxidant, biologically active compounds that accumulate in tissues in association with hyperglycaemia, hyperlipidaemia and oxidative stress. This is a cross-sectional case-control study involving 80 patients with mild/severe psoriasis and 80 controls matched for age, sex and body mass index (40 with severe eczema, 40 healthy individuals). Patients and healthy individuals with a smoking habit, diabetes, dyslipidaemia, hypercholesterolaemia, hypertension or who were under systemic treatment were excluded from the study. Skin AGEs were measured in normal-appearing skin by a standard fluorescence technique, and blood AGEs (total AGEs, pentosidine and AGEs receptor) by enzyme-linked immunosorbent assay. Levels of cutaneous AGEs (p < 0.04), serum AGEs (p < 0.03) and pentosidine (p < 0.05) were higher in patients with severe psoriasis. Cutaneous AGEs correlated well with serum AGEs (r = 0.93, p < 0.0001) and with Psoriasis Area and Severity Index score (r = 0.91, p < 0.0001). Receptor levels were lower (p < 0.001) in severe psoriasis, and inversely correlated with disease severity (r = –0.71, p < 0.0002). Patients with severe psoriasis have accumulation of skin and serum AGEs, independent of associated metabolic disorders

POS1221 SARS-COV2 SEROLOGY SCREENING IN SPONDYLOARTHRITIS PATIENTS IN NORTH-EASTERN ITALY: A PILOT STUDY

Background:Serology could help defining the real extent of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV2) diffusion in the population, especially in individuals considered at higher risk of SARS-CoV2 infection (COVID-19), such as Spondiloarthritis (SpA) patients undergoing immunosuppressive therapy or health care workers (HCW). In fact, COVID-19 detection is complicated by the fact that many patients can be asymptomatic. In these cases, it has also been suggested that a weaker immune response might be elicited.In this context, the role of anti-cytokine targeted therapy –commonly used as treatment in SpA- is uncertain, as it is not clear whether it is detrimental or protective towards severe disease forms.Objectives:The aim of the study was to explore the potential role of serology in detecting previous contact with SARS-CoV2 in SpA patients and HCW, and compare the frequency of positive findings with a control population.Methods:Consecutive patients affected by axial or peripheral SpA, classified according to Assessment of SpondyloArthritis international Society (ASAS) criteria and undergoing cytokine-targeted therapy, as well as HCW and controls from the pre-COVID-19 era (control group, 2015) were recruited. In SpA patients, disease activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) and Disease Activity Score on 28-joint-count (DAS28).Sera from all patients were analysed through chemiluminescent analytical system (CLIA) for the presence of IgG and IgM anti-SARS-CoV2. Patients with a positive serological test (either IgM or IgG) additionally underwent real time Polymerase Chain Reaction (RT-PCR) in nasopharyngeal swabs in order to test for active infection. In SpA patients, serology was repeated after 3 months. Data across the 3 groups were compared by ANOVA or Chi-square, while comparison between 2 groups were conducted by Wilcoxon signed rank test or Chi-Square, for continuous and categorical data respectively. P ≤ 0.05 were considered as significant.Results:A total of 396 patients were recruited: 200 SpA, 95 HCW and 101 healthy controls. SpA patients were mostly (54%) males, with mean age 49.6 ±14.7 years, and all were treated with anti-TNFα (78%), anti-IL-17 (9%) and anti-IL-23 drugs (7%), or small molecules (6%). Their disease activity level was moderate-low as assessed by ASDAS (1.95 ±0.98) and DAS28 (2.33 ±2.02). Among HCW and controls, 35% and 62% were male, with mean age 46.7 ±12.9 and 50.6±10.6 respectively.Positive serology (IgM or IgG, or both) was found in 12.5% SpA patients, 8.4% HCW, 0% controls (p=0.001). Among these, IgM titres were higher in the SpA group than in HCW (2.76±2.94 versus 0.80±0.67 KU/L, p= 0.016), while IgG mean titres were lower in the SpA group than in HCW (0.88±3.18 KU/L versus 1.05±0.88, p= 0.035). SpA patients with positive serology more frequently reported COVID-19 like symptoms than those with negative serology (20% vs 4%, p=0.009) and 2 had COVID-19 as confirmed by RT-PCR, none with a severe disease course. None of the HCW reported symptoms or tested positive by RT-PCR. In the SpA patients, at 3 months, the mean IgM titre decreased from 2.76±2.93 to 2.38±2.95 (p=0.001), while the IgG titres decreased from 0.89±3.25 to 0.31±0.87 (p=ns). Interestingly, the IgM or IgG titer at a single-patient level did not seem to change much in terms of absolute value (Figure 1), except in one patient, with documented COVID-19 (positive RT-PCR), in whom IgG level even decreased at 3 months.Conclusion:Serology revealed that exposure to COVID-19 in SpA patients, as well as HCW, was higher than expected based on reported symptoms. Targeted anti-cytokine therapy could act as a protective factor for a severe disease course in SpA patients. However, in this population, IgG and IgM titres did not change in a clinically significant manner at 3 months, and patient did not seem to develop an immune profile consistent with durable response. This result could be due to a weaker immune response in mild infections, but further studies are warranted to clarify the pathophysiology beyond these observations.Figure 1.Disclosure of Interests:Augusta Ortolan: None declared, Chiara Cosma: None declared, Mariagrazia Lorenzin: None declared, Giacomo Cozzi: None declared, Andrea Doria Speakers bureau: Novartis, Abbvie, Pfizer, MSD, Janssen, Glaxosmithkline, Mario Plebani: None declared, Roberta Ramonda Speakers bureau: Novartis, Abbvie, Pfizer, MSD, Jansse