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Background: Many studies have shown that socioeconomic position (SEP) is associated with the incidence of malignant tumors at different sites. This study aims to estimate the association between educational level (as proxy for SEP) and cancer incidence and to understand whether the observed associations might be partially explained by lifestyle behaviors. Methods: The analyses were performed on data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, globally and by sex. We used Cox proportional hazards models together with mediation analysis to disentangle the total effect (TE) of educational level [measured through the Relative Index of Inequality (RII)] on cancer incidence into pure direct (PDE) and total indirect (TIE) effect, unexplained and explained by mediators, respectively. PDE and TIE were then combined to compute the proportions mediated (PM). Results: After an average of 14 years of follow-up, 52,422 malignant tumors were ascertained. Low educated participants showed higher risk of developing stomach, lung, kidney (in women), and bladder (in men) cancers, and, conversely, lower risk of melanoma and breast cancer (in post-menopausal women), when compared with more educated participants. Mediation analyses showed that portions of the TE of RII on cancer could be explained by site-specific related lifestyle behaviors for stomach, lung, and breast (in women). Conclusions: Cancer incidence in Europe is determined at least in part by a socioeconomically stratified distribution of risk factors. Impact: These observational findings support policies to reduce cancer occurrence by altering mediators, such as lifestyle behaviors, particularly focusing on underprivileged strata of the population.

Testing for the SARS-CoV-2 infection is critical for tracking the spread of the virus and controlling the transmission dynamics. In the early phase of the pandemic in Italy, the decentralized healthcare system allowed regions to adopt different testing strategies. The objective of this paper is to assess the impact of the extensive testing of symptomatic individuals and their contacts on the number of hospitalizations against a more stringent testing strategy limited to suspected cases with severe respiratory illness and an epidemiological link to a COVID-19 case. A Poisson regression modelling approach was adopted. In the first model developed, the cumulative daily number of positive cases and a temporal trend were considered as explanatory variables. In the second, the cumulative daily number of swabs was further added. The explanatory variable, given by the number of swabs over time, explained most of the observed differences in the number of hospitalizations between the two strategies. The percentage of the expected error dropped from 70% of the first, simpler model to 15%. Increasing testing to detect and isolate infected individuals in the early phase of an outbreak improves the capability to reduce the spread of serious infections, lessening the burden of hospitals.

Adherence to the Mediterranean diet (MD) has a preventive effect on colorectal cancer (CRC). Several biological mechanisms have been hypothesized to explain this effect, but the involvement of clinical mediators has not been experimentally proven. We examined the role of abdominal adiposity (i.e., waist-to-hip ratio, WHR) as a potential mediator of the relationship between the MD and CRC in the Italian centres of the European Prospective Investigation into Cancer and Nutrition. We evaluated the effect of the Italian Mediterranean Index (IMI) on WHR and of WHR on CRC risk. We then estimated the natural indirect effect (NIE, mediated by WHR) and the pure direct effect (PDE, unmediated) of IMI on CRC risk using mediation analyses, considering age, sex, education, physical activity, smoking and EPIC centre as confounders. Increased IMI was associated with significantly decreased odds of high WHR (odds ratio [OR] for an IMI of 6-11 vs. 0-1: 0.88, 95% confidence interval [CI]: 0.81-0.97). There was a positive relationship between WHR and CRC (hazard ratio [HR] for high vs. low WHR: 1.34, 95%CI: 1.09-1.66). The total effect of IMI was protective on CRC risk and was mainly explained by the PDE (HR for an IMI of 6-11 vs. 0-1: 0.51, 95%CI: 0.31-0.83), whereas the NIE was 1.00 (95%CI: 0.94-1.10). In this Mediterranean cohort, the protective effect of the MD on the development of CRC was not mediated by abdominal adiposity. Since this is the first study to investigate the mediating effect of abdominal obesity, other studies are needed to replicate this result.

Purpose To assess intra- and interobserver variability in the apparent diffusion coefficient (ADC) measurements of pleural abnormalities. Materials and Methods Diffusion-weighted magnetic resonance imaging was performed in 34 patients to characterize pleural abnormalities, with a 1.5T unit at b values of 0/150/500/800 sec/mm2. In two sessions held 3 months apart, on perfusion-free ADC maps, two independent readers measured the ADC of pleural abnormalities (two readings for each reader in each case) using different methods of region-of-interest (ROI) positioning. In three methods, freehand ROIs were drawn within tumor boundaries to encompass the entire lesion on one or more axial slices (whole tumor volume [WTV], three slices observer-defined [TSOD], single-slice [SS]), while in two methods one or more ROIs were placed on the more restricted areas (multiple small round ROI [MSR], one small round ROI [OSR]). Measurement variability between readings by each reader (intraobserver repeatability) and between readers in first reading (interobserver repeatability) were assessed using intraclass correlation coefficient (ICC) and coefficient of variation (CoV). Analysis of variance (ANOVA) was performed to compare ADC values between the different methods. The measurement time of each case for all methods in first reading was recorded and compared between methods and readers. Results All methods demonstrated good (MSR, OSR) and excellent (WTV, TSOD, SS) intra- and interreader agreement, with best and worst repeatability in WTV (lower ICC, 0.977; higher CoV, 3.5%) and OSR (lower ICC, 0.625; higher CoV, 22.8%), respectively. The lower 95% confidence interval of ICC resulted in fair to moderate agreement for OSR (up to 0.379) and in excellent agreement for WTV, TSV, and SS (up to 0.918). ADC values of OSR and MSR were significantly lower compared to other methods (P < 0.001). The OSR and SS required less measurement time (10 and 21/22 sec, respectively) compared to the others (P < 0.0001), while the WTV required the longest measurement time (132/134 sec) (P < 0.0001). Conclusion ADC measurements of pleural abnormalities are repeatable. The SS method has excellent repeatability, similar to WTV, but requires significantly less measurement time. Thus, its use should be preferred in clinical practice. Level of Evidence: 4 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:769–782

The biological mechanisms through which adherence to Mediterranean Diet (MD) protects against colon cancer (CC) are poorly understood. Evidence suggests that chronic inflammation may be implicated in the pathway. Both diet and CC are related to epigenetic regulation. We performed a nested case-control study on 161 pairs from the Italian component of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, in which we looked for the methylation signals in DNA extracted from leucocytes associated with both CC and MD in 995 CpGs located in 48 inflammation genes. The DNA methylation signals detected in this analysis were validated in a subgroup of 47 case-control pairs and further replicated (where validated) in 95 new pairs by means of pyrosequencing. Among the CpG sites selected a-priori in inflammation-related genes, seven CpG sites were found to be associated with CC status and with MD, in line with its protective effect. Only two CpG sites (cg17968347-SERPINE1 and cg20674490-RUNX3) were validated using bisulphite pyrosequencing and, after replication, we found that DNA methylation of cg20674490-RUNX3 may be a potential molecular mediator explaining the protective effect of MD on CC onset. The use of a ‘meet-in-the-middle’ approach to identify the overlap between exposure and predictive markers of disease is innovative in studies on the relationship between diet and cancer, in which exposure assessment is difficult and the mechanisms through which the nutrients exert their protective effect is largely unknown.

The main risk factor for bladder cancer (BC) is cigarette smoking, but also occupational exposure to carcinogens is relevant, causing about 4–10% of BC. We aimed at investigating the association between BC risk, occupations held in the past and exposure to occupational carcinogens, also assessing whether these associations were influenced by tumour grade. We pooled data from two Italian case–control studies on male BC, analyzing 893 cases and 978 controls. Occupations were classified using the International Standard Classification of Occupations and exposure to carcinogens was assigned using a validated Job Exposure Matrix. Logistic regression approach was used as well as a semi-Bayesian model, based on a priori information on exposure. A significantly increased BC risk was found for chemical engineering technicians, postmen, and lathe operators, but only, for the latter, the association remained significant after Bayesian control for type I error. Among carcinogens, cadmium and trichloroethylene were associated with BC. When analyzing data by grade, exposure to these carcinogens was associated with low-grade BC only. Our results suggest that monitoring workplaces to prevent exposure to carcinogenic agents is still an important task, which should be still given adequate importance in public health.

Excessive calorie intake and physical inactivity are considered key determinants of the rapid worldwide increase in obesity prevalence, however the relationship between diet and weight gain is complex. We investigated associations between adherence to a Mediterranean diet and long-term changes in weight and waist circumference in volunteers recruited to the Italian section of the prospective European Prospective Investigation into Cancer and Nutrition (EPIC). We investigated 32,119 cohort members who provided anthropometric measures at recruitment and updated information on recall a mean of 12 years later. Adherence to a Mediterranean diet was assessed using the Italian Mediterranean Index (score range 0–11). Associations between index score and weight and waist changes were assessed by multivariate linear regression models. Risks of developing overweight/obesity and abdominal obesity were investigated by multivariate logistic models. Increasing Italian Mediterranean Index score (indicating better adherence) was associated with lower 5-year weight change in volunteers of normal weight at baseline (β −0.12, 95% CI −0.16 to −0.08 for 1 tertile increase in score), but not in those overweight/obese at baseline (P interaction between Index score and BMI 0.0001). High adherence was also associated with reduced risk of becoming overweight/obese (OR 0.91, 95% CI 0.84–0.99 third vs. first tertile); smaller 5-year change in waist circumference (β −0.09, 95% CI −0.14 to −0.03 for 1 tertile increase in score); and lower risk of abdominal obesity (OR 0.91, 95% CI 0.84–0.99 third vs. first tertile). Adherence to a traditional Italian Mediterranean diet may help prevent weight gain and abdominal obesity.

As graft survival in pediatric LT is often affected by progressive fibrosis, numerous centers carry out protocol liver biopsies. Follow-up biopsy protocols differ from center to center, but all biopsies are progressively spaced out, as time from transplant increases. Therefore, there is a need for non-invasive techniques to evaluate graft fibrosis progression in those children who have no clinical or serological signs of liver damage. Indirect markers, such as the APRI, should be relied on with caution because their sensitivity in predicting fibrosis can be strongly influenced by the etiology of liver disease, severity of fibrosis, and patient age. A valid alternative could be TE, a non-invasive technique already validated in adults, which estimates the stiffness of the cylindrical volume of liver tissue, 100-fold the size of a standard needle biopsy sample. The aims of this study were to evaluate the reliability of TE in children after LT and to compare both the TE and the APRI index results with the histological scores of fibrosis on liver biopsies. A total of 36 pediatric LT recipients were studied. All patients underwent both TE and biopsy within a year (median interval -0.012 months) at an interval from LT of 0.36 to 19.47 years (median 3.02 years). Fibrosis was assessed on the biopsy specimens at histology and staged according to METAVIR. There was a statistically significant correlation between TE stiffness values and METAVIR scores (P = .005). The diagnostic accuracy of TE for the diagnosis of significant fibrosis (F ≥ 2) was measured as the area under the curve (AUROC = 0.865), and it demonstrated that the method had a good diagnostic performance. APRI was not so accurate in assessing graft fibrosis when compared to METAVIR (AUROC = 0.592). A liver stiffness cutoff value of 5.6 kPa at TE was identified as the best predictor for a significant graft fibrosis (METAVIR F ≥ 2) on liver biopsy, with a 75% sensitivity, a 95.8% specificity, a 90% positive predictive value, and an 88.5% negative predictive value. These data suggest that TE may represent a non-invasive, reliable tool for the assessment of graft fibrosis in the follow-up of LT children, alerting the clinicians to the indication for a liver biopsy, with the aim of reducing the number of protocol liver biopsies.

To prospectively evaluate usefulness of the apparent diffusion coefficient (ADC) in differentiating anterior mediastinal lymphoma from nonsuppressing normal thymus on chemical-shift MR, and to look at the relationship between patient age and ADC. Seventy-three young subjects (25 men, 48 women; age range, 9-29 years), who underwent chemical-shift MR and diffusion-weighted MR were divided into a normal thymus group (group A, 40 subjects), and a lymphoma group (group B, 33 patients). For group A, all subjects had normal thymus with no suppression on opposed-phase chemical-shift MR. Two readers measured the signal intensity index (SII) and ADC. Differences in SII and ADC between groups were tested using t-test. ADC was correlated with age using Pearson correlation coefficient. Mean SII±standard deviation was 2.7±1.8% for group A and 2.2±2.4% for group B, with no significant difference between groups (P=.270). Mean ADC was 2.48±0.38x10-3mm2/s for group A and 1.24±0.23x10-3mm2/s for group B. A significant difference between groups was found (P

Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed-up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen-Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval-CI 18-42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43-2.00), lymphoma (SIR 1.80, 95% CI 1.31-2.40), melanoma (2.12; 1.63-2.70), endometrium (2.18; 1.75-2.70) and kidney cancers (2.40; 1.57-3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post-menopausal status and a history of full-term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full-term pregnancy was inversely associated with the risk of second primary cancer. What's new? For the first time, researchers have used cohort data to show that people who survive breast cancer have a higher risk of developing another cancer later. By collecting data on 10,000 breast cancer patients over 11 years, these authors calculated a 30% boost in the patients' risk of developing a second primary malignancy, particularly colorectal cancer, lymphoma, melanoma, endometrial cancer, and kidney cancer. These findings, plus the data they collected on risk factors such as age, smoking, body mass index, and others, will help guide clinicians in screening procedures and follow up care for breast cancer patients.

Objective To assess the accuracy of 64-row computed tomography (CT) in the differential diagnosis of acute abdomen in the emergency department. Materials and Methods Prospective analysis of 181 patients with surgically treated acute abdomen. Results In 158/181 cases, CT was totally concordant with surgical repertoire. Partial concordance was found in 15 cases. Overall sensitivity was 87.3% when only cases of complete concordance were considered, 95.6% if also partial concordance cases were included. Conclusion CT showed high reliability in the differential diagnosis of acute abdomen surgically treated, although associated conditions can sometimes be missed.

Background: Preterm babies are at high risk of iron deficiency. Methods: We investigated current practices regarding iron prophylaxis in preterm and low birth weight newborns among Local Neonatal Units (LNUs, n = 74) and Neonatal Intensive Care Units (NICUs, n = 20) of three Italian Regions (Piemonte, Marche and Lazio). Results: Birth weight is considered an indicative parameter in only 64% of LNUs and 71% of NICUs, with a significant difference between LNUs in the three regions (86%, 20% and 62%, respectively; p

To assess intra- and interobserver variability in the apparent diffusion coefficient (ADC) measurements of pleural abnormalities.Diffusion-weighted magnetic resonance imaging was performed in 34 patients to characterize pleural abnormalities, with a 1.5T unit at b values of 0/150/500/800 sec/mmAll methods demonstrated good (MSR, OSR) and excellent (WTV, TSOD, SS) intra- and interreader agreement, with best and worst repeatability in WTV (lower ICC, 0.977; higher CoV, 3.5%) and OSR (lower ICC, 0.625; higher CoV, 22.8%), respectively. The lower 95% confidence interval of ICC resulted in fair to moderate agreement for OSR (up to 0.379) and in excellent agreement for WTV, TSV, and SS (up to 0.918). ADC values of OSR and MSR were significantly lower compared to other methods (P0.001). The OSR and SS required less measurement time (10 and 21/22 sec, respectively) compared to the others (P0.0001), while the WTV required the longest measurement time (132/134 sec) (P0.0001).ADC measurements of pleural abnormalities are repeatable. The SS method has excellent repeatability, similar to WTV, but requires significantly less measurement time. Thus, its use should be preferred in clinical practice.4 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:769-782.

Background Endometrial cancer is the fourth most common cancer in European women. The major risk factors for endometrial cancer are related to the exposure of endometrium to estrogens not opposed to progestogens, that can lead to a chronic endometrial inflammation. Diet may play a role in cancer risk by modulating chronic inflammation. Methods In the framework of a case-control study, we recruited 297 women with newly diagnosed endometrial cancer and 307 controls from Northern Italy. Using logistic regression, we investigated the role of fruit and vegetable intake, adherence to the Mediterranean diet (MD), and the dietary inflammatory index (DII) in endometrial cancer risk. Results Women in the highest quintile of vegetable intake had a statistically significantly lower endometrial cancer risk (adjusted OR 5th quintile vs 1st quintile: 0.34, 95% CI 0.17-0.68). Women with high adherence to the MD had a risk of endometrial cancer that was about half that of women with low adherence to the MD (adjusted OR: 0.51, 95% CI 0.39-0.86). A protective effect was detected for all the lower quintiles of DII, with the highest protective effect seen for the lowest quintile (adjusted OR 5th quintile vs 1st quintile: 3.28, 95% CI 1.30-8.26). Conclusions These results suggest that high vegetable intake, adherence to the MD, and a low DII are related to a lower endometrial cancer risk, with several putative connected biological mechanisms that strengthen the biological plausibility of this association. Electronic supplementary material The online version of this article (10.1186/s12885-017-3754-y) contains supplementary material, which is available to authorized users.

An approximate solution to an integral equation for the first-crossing-time density of a Wiener process with constant amplitude jumps separated by exponential random times is shown to hold under suitable conditions and to explain some multimodal behaviors.

We report data regarding kinetic of response to oral iron in 34 iron deficiency anemia children. Twenty-four/34 patients (70.5%) reached reference value of hemoglobin (Hb) concentration for age and sex at day + 30 from the beginning of treatment (complete early responders (CERs)), and 4/34 (12%) reached an Hb concentration at least 50% higher than the original (partial early responders (PERs)). CHr at T1 (within 7 days from the beginning of treatment) was significantly different in the different groups (22.95 in CERs versus 18.41 in other patients;p=0.001; 22.42 in early responders versus 18.07 in NERs;p=0.001). Relative increase of CHr from T0 to T1 resulted significantly higher in CERs than in other patients (0.21 versus 0.11,p=0.042) and in early responders than in NERs (0.22 versus 0.004,p=0.006). Multivariate logistic models revealed a higher probability of being a complete early responder due to relative increase of ARC from T0 to T1 [OR (95% CI) = 44.95 (1.54–1311.98)] and to CHr at T1 [OR (95% CI) =3.18 (1.24–8.17)]. Our preliminary data confirm CHr as early and accurate predictor of hematological response to oral iron.

The adduction of fumaric acid to the sulfhydryl group of certain cysteine (Cys) residues in proteins via a Michael-like reaction leads to the formation of S-(2-succino)cysteine (2SC) sites. Although its role remains to be fully understood, this post-translational Cys modification (protein succination) has been implicated in the pathogenesis of diabetes/obesity and fumarate hydratase-related diseases. In this study, theoretical approaches to address sequence- and 3D-structure-based features possibly underlying the specificity of protein succination have been applied to perform the first analysis of the available data on the succinate proteome. A total of 182 succinated proteins, 205 modifiable, and 1750 non-modifiable sites have been examined. The rate of 2SC sites per protein ranged from 1 to 3, and the overall relative abundance of modifiable sites was 10.8%. Modifiable and non-modifiable sites were not distinguishable when the hydrophobicity of the Cys-flaking peptides, the acid dissociation constant value of the sulfhydryl groups, and the secondary structure of the Cys-containing segments were compared. By contrast, significant differences were determined when the accessibility of the sulphur atoms and the amino acid composition of the Cys-flaking peptides were analysed. Based on these findings, a sequence-based score function has been evaluated as a descriptor for Cys residues. In conclusion, our results indicate that modifiable and non-modifiable sites form heterogeneous subsets when features often discussed to describe Cys reactivity are examined. However, they also suggest that some differences exist, which may constitute the baseline for further investigations aimed at the development of predictive methods for 2SC sites in proteins.

To evaluate the usefulness of computed tomography (CT) and chemical-shift magnetic resonance imaging (MRI) in patients with myasthenia gravis (MG) for differentiating thymoma (THY) from thymic lymphoid hyperplasia (TLH) and normal thymus (NT), and to determine which technique is more accurate.Eighty-three patients with generalised MG who underwent surgery were divided into the TLH/NT group (A; 65 patients) and THY group (B; 24 patients). Differences in qualitative characteristics and quantitative data (CT: radiodensity in Hounsfield units; MRI: signal intensity index [SII]) between groups were tested using Fisher's exact test and Student's t-test. Logistic regression models were estimated for both qualitative and quantitative analyses. At quantitative analysis, discrimination abilities were determined according to the area under the receiver operating characteristic (ROC) curve (AUROC) with computation of optimal cut-off points. The diagnostic accuracies of CT and MRI were compared using McNemar's test.At qualitative assessment, MRI had higher accuracy than CT (96.4%, 80/83 and 86.7%, 72/83, respectively). At quantitative analysis, both the radiodensity and SII were significantly different between groups (p0.0001). For CT, at quantitative assessment, the AUROC of the radiodensity in discriminating between groups was 0.904 (optimal cut-off point, 20 HU) with an accuracy of 77.1% (64/83). For MRI, the AUROC of the SII was 0.989 (optimal cut-off point, 7.766%) with an accuracy of 96.4% (80/83), which was significantly higher than CT (p0.0001). By using optimal cut-off points for cases with an erroneous diagnosis at qualitative assessment, accuracy improved both for CT (89.2%, 74/83) and MRI (97.6%, 81/83).Quantitative analysis is useful in evaluating patients with MG and improves the diagnostic accuracy of CT and MRI based on qualitative assessment. Chemical-shift MRI is more reliable than CT in differentiating THYs from non-thymomatous conditions.

To evaluate the usefulness of diffusion-weighted magnetic resonance for distinguishing thymomas according to WHO and Masaoka-Koga classifications and in predicting disease-free survival (DFS) by using the apparent diffusion coefficient (ADC). Forty-one patients were grouped based on WHO (low-risk vs. high-risk) and Masaoka-Koga (early vs. advanced) classifications. For prognosis, seven patients with recurrence at follow-up were grouped separately from healthy subjects. Differences on ADC levels between groups were tested using Student-t testing. Logistic regression models and areas under the ROC curve (AUROC) were estimated. Mean ADC values were different between groups of WHO (low-risk = 1.58 ± 0.20 × 10-3mm2/sec; high-risk = 1.21 ± 0.23 × 10-3mm2/sec; p

OBJECTIVES The objective of this study was to prospectively investigate the usefulness of chemical-shift and diffusion-weighted (DW) magnetic resonance imaging (MRI) in patients with myasthenia gravis (MG) for distinguishing thymic lymphoid hyperplasia (TLH), normal thymus (NT), and thymoma (THY) by using the signal intensity index (SII) and the apparent diffusion coefficient (ADC). MATERIALS AND METHODS We examined 87 subjects (44 males, 43 females; range, 15-71 years) with generalized MG and antibodies to the acetylcholine receptor seropositivity who underwent surgery. They were divided into a TLH/NT group (A, 64 patients; TLH, 49; NT, 15) and a THY group (B, 24 patients; nonadvanced THY, 15; advanced THY, 9) on the basis of histological findings. One patient with contemporary findings of TLH and nonadvanced THY at histology was listed in both groups (87 subjects, 88 findings). Chemical-shift MRI (CS-MRI) was performed with dual-echo acquisition, and the SII was measured for each subject. Diffusion-weighted MRI was performed at b values of 0, 150, 500, and 800 s/mm, and the ADC value was obtained on the ADC map after excluding the 0-s/mm b value diffusion weighting. All measures were performed independently by 2 radiologists, and interreader agreement was assessed by calculating the intraclass correlation coefficient. Differences on SII and ADC levels between the groups and subgroups were tested using the Student t test. Logistic regression models were estimated, and discrimination abilities were individuated according to the area under the receiver operating characteristic curve (AUROC). The optimal cut points for the differentiation of the groups and subgroups were obtained by using the Youden index. RESULTS The interreader agreement was excellent (intraclass correlation coefficient: SII, 0.998; ADC, 0.944). For CS-MRI, the mean (SD) SII value was significantly different between the groups (A, 36.37% [12.60%]; B, -0.06% [3.85%]; P < 0.001). No overlap in indexes was found with sensitivity, specificity, and cut point of 100%, 100%, and 6.37%, respectively. Conversely, the mean SII value was not different between the subgroups of each group (A, P = 0.607; B, P = 0.252). For DW-MRI, the mean (SD) ADC values were significantly different between the groups (A, 1.92 [0.21] × 10·mm/s; B, 1.36 [0.33] × 10 mm/s; P < 0.001) and between the subgroups of group A (TLH, 1.86 [0.17] × 10 mm/s; NT, 2.10 [0.23] × 10 mm/s; P = 0.002), although overlapped values were found. The AUROC of ADC in discriminating TLH/NT from THY was 0.931 (95% confidence interval, 0.863-0.998), and the optimal cut point for this distinction was 1.625 × 10 mm/s (Youden index, J = 0.760) with sensitivity of 96.8% and specificity of 79.2%. For the subgroups of group A, the AUROC of ADC in discriminating NT from TLH was 0.794 (95% confidence interval, 0.666-0.923), and the optimal cut point for this distinction was 2.01 × 10 mm/s (Youden index, J = 0.458) with sensitivity of 66.7% and specificity of 79.2%. CONCLUSIONS CS-MRI and DW-MRI are both useful tools for examining patients with MG. The SII is more accurate than the ADC to differentiate TLH and NT from THY (AUROC, 1.000 and 0.931, respectively). Furthermore, the ADC is a noninvasive parameter that could be used for distinguishing TLH from NT, which is useful in selecting patients for surgery because, for nonthymomatous MG, acceptable rates of complete stable remission after thymectomy are found in TLH but not in NT.

A reliable Monte Carlo method for the evaluation of first passage times of diffusion processes through boundaries is proposed. A nested algorithm that simulates the first passage time of a suitable tied-down process is introduced to account for undetected crossings that may occur inside each discretization interval of the stochastic differential equation associated to the diffusion. A detailed analysis of the performances of the algorithm is then carried on both via analytical proofs and by means of some numerical examples. The advantages of the new method with respect to a previously proposed numerical-simulative method for the evaluation of first passage times are discussed. Analytical results on the distribution of tied-down diffusion processes are proved in order to provide a theoretical justification of the Monte Carlo method.

Improved simulation schemes for the evaluation of first passage times through boundaries for one dimensional diffusion processes can be obtained taking into account possible crossings that occur inside each simulation interval. Approximated evaluations for the probabilities of such events are proposed and the error connected with their use in a simulation algorithm is discussed. Two examples are finally given to illustrate the features of the method.

The interspike distribution can be modelled as the first-passage-time distribution of suitable diffusion processes with biologically meaningful boundaries. Since various mathematical difficulties arise when one attempts to obtain closed form solutions for first-passage-time problems, one can resort to simulation methods in order to study the problem. In this paper we pinpoint possible overestimations connected with simulations of first-passage-times for diffusion processes and propose a suitable simulation technique to determine the moments and the distribution of the firing times. After checking the validity of the proposed method in some instances where numerical evaluations for such quantities are available, we apply the simulation algorithm to model the spiking activity by means of a particular diffusion process constrained by a suitable time varying threshold.

Aiming at an improvement of the existing neuronal models, we consider a mixed process ensuing from the superposition of continuous diffusions and of Poisson time-distributed sequence of impulses and focus our attention on the moments of the firing time. In particular, we consider three different instances: the large jumps model in which each jump causes the neuron firing, the reset model characterized by jumps towards the resting potential and a more general model where constant amplitude excitatory and inhibitory jumps are superimposed on diffusion. By resorting to analytical arguments and to numerical computations, the main behavioral differences of the considered models are outlined.

A new, non–parametric and binless estimator for the mutual information of a d–dimensional random vector is proposed. First of all, an equation that links the mutual information to the entropy of a suitable random vector with uniformly distributed components is deduced. When d = 2 this equation reduces to the well known connection between mutual information and entropy of the copula function associated to the original random variables. Hence, the problem of estimating the mutual information of the original random vector is reduced to the estimation of the entropy of a random vector obtained through a multidimensional transformation. The estimator we propose is a two–step method: first estimate the transformation and obtain the transformed sample, then estimate its entropy. The properties of the new estimator are discussed through simulation examples and its performances are compared to those of the best estimators in the literature. The precision of the estimator converges to values of the same order of magnitude of the best estimator tested. However, the new estimator is unbiased even for larger dimensions and smaller sample sizes, while the other tested estimators show a bias in these cases.

Mathematical models are an important tool for neuroscientists. During the last 30 years many papers have appeared on single neuron description and specifically on stochastic Integrate and Fire models. Analytical results have been proved and numerical and simulation methods have been developed for their study. Recent reviews collect the main features of these models but do not focus on the methodologies employed to obtain them. The aim of this paper is to fill this gap by upgrading old reviews. The idea is to collect the existing methods and the available analytical results for the most common one dimensional stochastic Integrate and Fire models to make them available for studies on networks. An effort to unify the mathematical notation is also made. The review is divided in two parts: 1. Derivation of the models with the list of the available closed forms expressions for their characterization. 2. Presentation of the existing mathematical and statistical methods for the study of these models.

The aim of the present study was to determine the effects of exclusive oral iron supplementation (iron sulphate 2 mg/kg/die) in asymptomatic children with severe iron-deficiency anemia [median hemoglobin (Hb) level before treatment 6.3 g/dL; range 4.5 to 7 g/dL] and to investigate the accuracy of Hb, reticulocyte hemoglobin content (CHr), and absolute reticulocyte count (ARC) as markers for monitoring early response to treatment. The increase in ARC and CHr was statistically significant at day +3. There was a significant association between suitable logarithmic functions of the percentage increase in CHr and ARC at day +3 and the fraction of required Hb increase compared with baseline to reach the mean reference value for age and sex at day +14. If these results are confirmed in a larger population, ARC and CHr could be considered affordable and widely available markers to detect early responders to oral iron therapy, and to switch unresponsive children to parenteral iron supplementation or transfusion.

Neural membrane potential data are necessarily conditional on observation being prior to a firing time. In a stochastic leaky integrate-and-fire model, this corresponds to conditioning the process on not crossing a boundary. In the literature, simulation and estimation have almost always been done using unconditioned processes. In this letter, we determine the stochastic differential equations of a diffusion process conditioned to stay below a level S up to a fixed time t1 and of a diffusion process conditioned to cross the boundary for the first time at t1. This allows simulation of sample paths and identification of the corresponding mean process. Differences between the mean of free and conditioned processes are illustrated, as well as the role of noise in increasing these differences.

The relative effects of two components of mountain environmental heterogeneity, altitude (1500, 1700 and 2000 m a.s.l.) and habitat (pastures, coniferous forests, wet meadows, scrub and anthropogenic woods) on the diversity of dung beetles in an Italian alpine valley were determined. The additive gamma diversity analysis indicated that differences among habitats (ßH) were always smaller than those among altitudes (ßA), irrespective of the measures used; it also showed that the contribution of ßA to γ-diversity was higher than expected by chance for all the measures of species diversity used, whereas the contribution of ßH was significantly higher in the case of one measure only. Generalized linear models confirmed that altitude was the most important factor associated with local diversity, with all the diversity parameters considered progressively and significantly increasing with increasing altitude. Indicator species analyses revealed that dung beetle altitudinal and habitat diversity patterns depended on local choice of species, with preferences for altitudinal levels being more numerous and apparent than those for habitats. Despite the minor effect of habitat differences, comparing a three-habitat with a single-habitat scenario it was possible to demonstrate that greater habitat heterogeneity is associated with a significantly greater diversity of dung beetles. This study suggests that preservation of local environmental heterogeneity by means of traditional pastoral activities should be encouraged as a means of conserving the diversity of dung beetle species in the Alps.

We consider a sample $${\left\{T_n\right\}_{1\leq n\leq N}}$$ of i.i.d. times and we interpret each item as the first-passage time (FPT) of a diffusion process through a constant boundary. The problem is to estimate the parameters characterizing the underlying diffusion process through the experimentally observable FPT’s. Recently in Ditlevsen and Lanský (Phys Rev E 71, 2005) and Ditlevsen and Lanský (Phys Rev E 73, 2006) closed form estimators have been proposed for neurobiological applications. Here we study the asymptotic properties (consistency and asymptotic normality) of the class of moment type estimators for parameters of diffusion processes like those in Ditlevsen and Lanský (Phys Rev E 71, 2005) and Ditlevsen and Lanský (Phys Rev E 73, 2006). Furthermore, to make our results useful for application instances we establish upper bounds for the rate of convergence of the empirical distribution of each estimator to the normal density. Applications are also considered by means of simulated experiments in a neurobiological context.

To relate the noise intensity with a periodically modulated input signal in a single neuron stochastic model we introduce a diffusion model with both time modulated drift and diffusion coefficient. Such a model is the continuous version of a Stein model with time oscillating frequencies for the Poisson processes describing the inputs impinging on the neuron. We focus here on some aspects of the resonance phenomenon for such a model. We compare the corresponding interspike interval distribution with the analogous distribution for a model sharing the same parameter values, but with constant noise intensity. Examples with two different levels for this noise intensity are discussed. The enhancement of the height of the peaks in the interspike interval distribution appearing at the modulation period, the improvement of the phase locking behavior and an enlargement of the noise ranges where a resonance like behavior arises are the main features observed in the considered cases.

The effects of taking into account in a perfect integrate and fire model of neuronal activity the spatial localization of the synapses are studied by superposing to the diffusion a simple discrete jump component. Different criteria are employed to assess the role of excitatory and inhibitory discrete contributions. Comparisons are performed with respect to the case where contributions coming from synapses more distal from the trigger zone are summed up in a continuous model. A systematic study of the output frequency and of the inter spike interval coefficient of variation (CV) is performed by means of examples as the model parameters are varied.

The article compares two of the most followed indices in the monitoring of COVID-19 epidemic cases: the Rt and the RDt indices. The first was disseminated by the Italian National Institute of Health (ISS) and the second, which is more usable due to the lower difficulty of calculation and the availability of data, was adopted by various regional and local institutions. The rationale for the Rt index refers to that for the R0 index, the basic reproduction number, which is used by infectivologists as a measure of contagiousness of a given infectious agent in a completely susceptible population. The RDt index, on the other hand, is borrowed from the techniques of time series analysis for the trend of an event measurement that develops as a function of time. The RDt index does not take into account the time of infection, but the date of the diagnosis of positivity and for this reason it is defined as diagnostic replication index, as it aims to describe the intensity of the development of frequency for cases recognized as positive in the population. The comparison between different possible applications of the methods and the use of different types of monitoring data was limited to four areas for which complete individual data were available in March and April 2020. The main problems in the use of Rt, which is based on the date of symptoms onset, arise from the lack of completeness of this information due both to the difficulty in the recording and to the absence in asymptomatic subjects. The general trend of RDt, at least at an intermediate lag of 6 or 7 days, is very similar to that of Rt, as confirmed by the very high value of the correlation index between the two indices. The maximum correlation between Rt and RDt is reached at lag 7 with a value of R exceeding 0.97 (R2=0.944). The two indices, albeit formally distinct, are both valid; they show specific aspects of the phenomenon, but provide basically similar information to the public health decision-maker. Their distinction lies not so much in the method of calculation, rather in the use of different information, i.e., the beginning of symptoms and the swabs outcome. Therefore, it is not appropriate to make a judgment of preference for one of the two indices, but only to invite people to understand their different potentials so that they can choose the one they consider the most appropriate for the purpose they want to use it for.