Climatological analysis of temperature and salinity fields in the Mediterranean sea

A climatological field is a mean gridded field that represents the monthly or seasonal trend of an ocean parameter. This instrument allows to understand the physical conditions and physical processes of the ocean water and their impact on the world climate. To construct a climatological field, it is necessary to perform a climatological analysis on an historical dataset. In this dissertation, we have constructed the temperature and salinity fields on the Mediterranean Sea using the SeaDataNet 2 dataset. The dataset contains about 140000 CTD, bottles, XBT and MBT profiles, covering the period from 1900 to 2013. The temperature and salinity climatological fields are produced by the DIVA software using a Variational Inverse Method and a Finite Element numerical technique to interpolate data on a regular grid. Our results are also compared with a previous version of climatological fields and the goodness of our climatologies is assessed, according to the goodness criteria suggested by Murphy (1993). Finally the temperature and salinity seasonal cycle for the Mediterranean Sea is described.

Multicentre study for a robust protocol in single-voxel spectroscopy: quantification of MRS signals by time-domain fitting algorithms

Magnetic Resonance Spectroscopy (MRS) is an advanced clinical and research application which guarantees a specific biochemical and metabolic characterization of tissues by the detection and quantification of key metabolites for diagnosis and disease staging. The "Associazione Italiana di Fisica Medica (AIFM)" has promoted the activity of the "Interconfronto di spettroscopia in RM" working group. The purpose of the study is to compare and analyze results obtained by perfoming MRS on scanners of different manufacturing in order to compile a robust protocol for spectroscopic examinations in clinical routines. This thesis takes part into this project by using the GE Signa HDxt 1.5 T at the Pavillion no. 11 of the S.Orsola-Malpighi hospital in Bologna. The spectral analyses have been performed with the jMRUI package, which includes a wide range of preprocessing and quantification algorithms for signal analysis in the time domain. After the quality assurance on the scanner with standard and innovative methods, both spectra with and without suppression of the water peak have been acquired on the GE test phantom. The comparison of the ratios of the metabolite amplitudes over Creatine computed by the workstation software, which works on the frequencies, and jMRUI shows good agreement, suggesting that quantifications in both domains may lead to consistent results. The characterization of an in-house phantom provided by the working group has achieved its goal of assessing the solution content and the metabolite concentrations with good accuracy. The goodness of the experimental procedure and data analysis has been demonstrated by the correct estimation of the T2 of water, the observed biexponential relaxation curve of Creatine and the correct TE value at which the modulation by J coupling causes the Lactate doublet to be inverted in the spectrum. The work of this thesis has demonstrated that it is possible to perform measurements and establish protocols for data analysis, based on the physical principles of NMR, which are able to provide robust values for the spectral parameters of clinical use.

Memory for Tune Titles after Organized or Unorganized Presentation

Two experiments investigated the structure of memory for titles of 54 familiar tunes. The titles were presented in the form of a hierarchy, with nodes labeled by genre (e.g., Rock or Patriotic). Four groups of subjects received logical or randomized titles, and logical or randomized labels. Goodness of label and title structure had equal and additive beneficial effects on recall with a 3-min exposure of the stimuli. With a 4-min exposure, good title structure became a larger contributor to good recall. Clustering analyses suggested that subjects were mentally representing the tune titles hierarchically, even when presentation was random.

Modeling Breastmilk Infectivity in HIV-1 Infected Mothers

Estimation of breastmilk infectivity in HIV-1 infected mothers is difficult because transmission can occur while the fetus is in-utero, during delivery, or through breastfeeding. Since transmission can only be detected through periodic testing, however, it may be impossible to determine the actual mode of transmission in any individual child. In this paper we develop a model to estimate breastmilk infectivity as well as the probabilities of in-utero and intrapartum transmission. In addition, the model allows separate estimation of early and late breastmilk infectivity and individual variation in maternal infectivity. Methods for hypothesis testing of binary risk factors and a method for assessing goodness of fit are also described. Data from a randomized trial of breastfeeding versus formula feeding among HIV-1 infected mothers in Nairobi, Kenya are used to illustrate the methods.

Cholesky Residuals for Assessing Normal Errors in a Linear Model with Correlated Outcomes: Technical Report

Despite the widespread popularity of linear models for correlated outcomes (e.g. linear mixed models and time series models), distribution diagnostic methodology remains relatively underdeveloped in this context. In this paper we present an easy-to-implement approach that lends itself to graphical displays of model fit. Our approach involves multiplying the estimated margional residual vector by the Cholesky decomposition of the inverse of the estimated margional variance matrix. The resulting "rotated" residuals are used to construct an empirical cumulative distribution function and pointwise standard errors. The theoretical framework, including conditions and asymptotic properties, involves technical details that are motivated by Lange and Ryan (1989), Pierce (1982), and Randles (1982). Our method appears to work well in a variety of circumstances, including models having independent units of sampling (clustered data) and models for which all observations are correlated (e.g., a single time series). Our methods can produce satisfactory results even for models that do not satisfy all of the technical conditions stated in our theory.

Model Checking for ROC Regression Analysis

The Receiver Operating Characteristic (ROC) curve is a prominent tool for characterizing the accuracy of continuous diagnostic test. To account for factors that might invluence the test accuracy, various ROC regression methods have been proposed. However, as in any regression analysis, when the assumed models do not fit the data well, these methods may render invalid and misleading results. To date practical model checking techniques suitable for validating existing ROC regression models are not yet available. In this paper, we develop cumulative residual based procedures to graphically and numerically assess the goodness-of-fit for some commonly used ROC regression models, and show how specific components of these models can be examined within this framework. We derive asymptotic null distributions for the residual process and discuss resampling procedures to approximate these distributions in practice. We illustrate our methods with a dataset from the Cystic Fibrosis registry.

Prediction of first coronary events with the Framingham score: a systematic review

BACKGROUND: Uncertainty exists about the performance of the Framingham risk score when applied in different populations. OBJECTIVE: We assessed calibration of the Framingham risk score (ie, relationship between predicted and observed coronary event rates) in US and non-US populations free of cardiovascular disease. METHODS: We reviewed studies that evaluated the performance of the Framingham risk score to predict first coronary events in a validation cohort, as identified by Medline, EMBASE, BIOSIS, and Cochrane library searches (through August 2005). Two reviewers independently assessed 1496 studies for eligibility, extracted data, and performed quality assessment using predefined forms. RESULTS: We included 25 validation cohorts of different population groups (n = 128,000) in our main analysis. Calibration varied over a wide range from under- to overprediction of absolute risk by factors of 0.57 to 2.7. Risk prediction for 7 cohorts (n = 18658) from the United States, Australia, and New Zealand was well calibrated (corresponding figures: 0.87-1.08; for the 5 biggest cohorts). The estimated population risks for first coronary events were strongly associated (goodness of fit: R2 = 0.84) and in good agreement with observed risks (coefficient for predicted risk: beta = 0.84; 95% CI 0.41-1.26). In 18 European cohorts (n = 109499), the corresponding figures indicated close association (R2 = 0.72) but substantial overprediction (beta = 0.58, 95% CI 0.39-0.77). The risk score was well calibrated on the intercept for both population clusters. CONCLUSION: The Framingham score is well calibrated to predict first coronary events in populations from the United States, Australia, and New Zealand. Overestimation of absolute risk in European cohorts requires recalibration procedures.

Integration of Truncated Distributions in Exponential Family with Simulation Models of Logistics and Supply Chain Management

Truncated distributions of the exponential family have great influence in the simulation models. This paper discusses the truncated Weibull distribution specifically. The truncation of the distribution is achieved by the Maximum Likelihood Estimation method or combined with the expectation and variance expressions. After the fitting of distribution, the goodness-of-fit tests (the Chi-Square test and the Kolmogorov-Smirnov test) are executed to rule out the rejected hypotheses. Finally the distributions are integrated in various simulation models, e. g. shipment consolidation model, to compare the influence of truncated and original versions of Weibull distribution on the model.

A multifactorial histopathologic score for the prediction of prognosis of resected esophageal adenocarcinomas after neoadjuvant chemotherapy

BACKGROUND For esophageal adenocarcinoma treated with neoadjuvant chemotherapy, postoperative staging classifications initially developed for non-pretreated tumors may not accurately predict prognosis. We tested whether a multifactorial TNM-based histopathologic prognostic score (PRSC), which additionally applies to tumor regression, may improve estimation of prognosis compared with the current Union for International Cancer Control/American Joint Committee on Cancer (UICC) staging system. PATIENTS AND METHODS We evaluated esophageal adenocarcinoma specimens following cis/oxaliplatin-based therapy from two separate centers (center 1: n = 280; and center 2: n = 80). For the PRSC, each factor was assigned a value from 1 to 2 (ypT0-2 = 1 point; ypT3-4 = 2 points; ypN0 = 1 point; ypN1-3 = 2 points; ≤50 % residual tumor/tumor bed = 1 point; >50 % residual tumor/tumor bed = 2 points). The three-tiered PRSC was based on the sum value of these factors (group A: 3; group B: 4-5; group C: 6) and was correlated with patients' overall survival (OS). RESULTS The PRSC groups showed significant differences with respect to OS (p < 0.0001; hazard ratio [HR] 2.2 [95 % CI 1.7-2.8]), which could also be demonstrated in both cohorts separately (center 1 p < 0.0001; HR 2.48 [95 % CI 1.8-3.3] and center 2 p = 0.015; HR 1.7 [95 % CI 1.1-2.6]). Moreover, the PRSC showed a more accurate prognostic discrimination than the current UICC staging system (p < 0.0001; HR 1.15 [95 % CI 1.1-1.2]), and assessment of two goodness-of-fit criteria (Akaike Information Criterion and Schwarz Bayesian Information Criterion) clearly supported the superiority of PRSC over the UICC staging. CONCLUSION The proposed PRSC clearly identifies three subgroups with different outcomes and may be more helpful for guiding further therapeutic decisions than the UICC staging system.

Prognostic implications of the seventh edition of the international union against cancer classification for patients with gastric cancer: the Western experience of patients treated in a single-center European institution

PURPOSE Validity of the seventh edition of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging systems for gastric cancer has been evaluated in several studies, mostly in Asian patient populations. Only few data are available on the prognostic implications of the new classification system on a Western population. Therefore, we investigated its prognostic ability based on a German patient cohort. PATIENTS AND METHODS Data from a single-center cohort of 1,767 consecutive patients surgically treated for gastric cancer were classified according to the seventh edition and were compared using the previous TNM/UICC classification. Kaplan-Meier analyses were performed for all TNM stages and UICC stages in a comparative manner. Additional survival receiver operating characteristic analyses and bootstrap-based goodness-of-fit comparisons via Bayesian information criterion (BIC) were performed to assess and compare prognostic performance of the competing classification systems. RESULTS We identified the UICC pT/pN stages according to the seventh edition of the AJCC/UICC guidelines as well as resection status, age, Lauren histotype, lymph-node ratio, and tumor grade as independent prognostic factors in gastric cancer, which is consistent with data from previous Asian studies. Overall survival rates according to the new edition were significantly different for each individual's pT, pN, and UICC stage. However, BIC analysis revealed that, owing to higher complexity, the new staging system might not significantly alter predictability for overall survival compared with the old system within the analyzed cohort from a statistical point of view. CONCLUSION The seventh edition of the AJCC/UICC classification was found to be valid with distinctive prognosis for each stage. However, the AJCC/UICC classification has become more complex without improving predictability for overall survival in a Western population. Therefore, simplification with better predictability of overall survival of patients with gastric cancer should be considered when revising the seventh edition.

Detection of nonrandom association of alleles from the distribution of the number of heterozygous loci in a sample.

The distribution of the number of heterozygous loci in two randomly chosen gametes or in a random diploid zygote provides information regarding the nonrandom association of alleles among different genetic loci. Two alternative statistics may be employed for detection of nonrandom association of genes of different loci when observations are made on these distributions: observed variance of the number of heterozygous loci (s2k) and a goodness-of-fit criterion (X2) to contrast the observed distribution with that expected under the hypothesis of random association of genes. It is shown, by simulation, that s2k is statistically more efficient than X2 to detect a given extent of nonrandom association. Asymptotic normality of s2k is justified, and X2 is shown to follow a chi-square (chi 2) distribution with partial loss of degrees of freedom arising because of estimation of parameters from the marginal gene frequency data. Whenever direct evaluations of linkage disequilibrium values are possible, tests based on maximum likelihood estimators of linkage disequilibria require a smaller sample size (number of zygotes or gametes) to detect a given level of nonrandom association in comparison with that required if such tests are conducted on the basis of s2k. Summarization of multilocus genotype (or haplotype) data, into the different number of heterozygous loci classes, thus, amounts to appreciable loss of information.

IN-VIVO CT DOSIMETRY DURING VIRTUAL COLONOSCOPY

Virtual colonoscopy (VC) is a minimally invasive means for identifying colorectal polyps and colorectal lesions by insufflating a patient’s bowel, applying contrast agent via rectal catheter, and performing multi-detector computed tomography (MDCT) scans. The technique is recommended for colonic health screening by the American Cancer Society but not funded by the Centers for Medicare and Medicaid Services (CMS) partially because of potential risks from radiation exposure. To date, no in‐vivo organ dose measurements have been performed for MDCT scans; thus, the accuracy of any current dose estimates is currently unknown. In this study, two TLDs were affixed to the inner lumen of standard rectal catheters used in VC, and in-vivo rectal dose measurements were obtained within 6 VC patients. In order to calculate rectal dose, TLD-100 powder response was characterized at diagnostic doses such that appropriate correction factors could be determined for VC. A third-order polynomial regression with a goodness of fit factor of R2=0.992 was constructed from this data. Rectal dose measurements were acquired with TLDs during simulated VC within a modified anthropomorphic phantom configured to represent three sizes of patients undergoing VC. The measured rectal doses decreased in an exponential manner with increasing phantom effective diameter, with R2=0.993 for the exponential regression model and a maximum percent coefficient of variation (%CoV) of 4.33%. In-vivo measurements yielded rectal doses ranged from that decreased exponentially with increasing patient effective diameter, in a manner that was also favorably predicted by the size specific dose estimate (SSDE) model for all VC patients that were of similar age, body composition, and TLD placement. The measured rectal dose within a younger patient was favorably predicted by the anthropomorphic phantom dose regression model due to similarities in the percentages of highly attenuating material at the respective measurement locations and in the placement of the TLDs. The in-vivo TLD response did not increase in %CoV with decreasing dose, and the largest %CoV was 10.0%.

Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma

BACKGROUND Renal cell carcinoma (RCC) is marked by high mortality rate. To date, no robust risk stratification by clinical or molecular prognosticators of cancer-specific survival (CSS) has been established for early stages. Transcriptional profiling of small non-coding RNA gene products (miRNAs) seems promising for prognostic stratification. The expression of miR-21 and miR-126 was analysed in a large cohort of RCC patients; a combined risk score (CRS)-model was constructed based on expression levels of both miRNAs. METHODS Expression of miR-21 and miR-126 was evaluated by qRT-PCR in tumour and adjacent non-neoplastic tissue in n = 139 clear cell RCC patients. Relation of miR-21 and miR-126 expression with various clinical parameters was assessed. Parameters were analysed by uni- and multivariate COX regression. A factor derived from the z-score resulting from the COX model was determined for both miRs separately and a combined risk score (CRS) was calculated multiplying the relative expression of miR-21 and miR-126 by this factor. The best fitting COX model was selected by relative goodness-of-fit with the Akaike information criterion (AIC). RESULTS RCC with and without miR-21 up- and miR-126 downregulation differed significantly in synchronous metastatic status and CSS. Upregulation of miR-21 and downregulation of miR-126 were independently prognostic. A combined risk score (CRS) based on the expression of both miRs showed high sensitivity and specificity in predicting CSS and prediction was independent from any other clinico-pathological parameter. Association of CRS with CSS was successfully validated in a testing cohort containing patients with high and low risk for progressive disease. CONCLUSIONS A combined expression level of miR-21 and miR-126 accurately predicted CSS in two independent RCC cohorts and seems feasible for clinical application in assessing prognosis.

Demographic model of the Swiss cattle population for the years 2009-2011 stratified by gender, age and production type

Demographic composition and dynamics of animal and human populations are important determinants for the transmission dynamics of infectious disease and for the effect of infectious disease or environmental disasters on productivity. In many circumstances, demographic data are not available or of poor quality. Since 1999 Switzerland has been recording cattle movements, births, deaths and slaughter in an animal movement database (AMD). The data present in the AMD offers the opportunity for analysing and understanding the dynamic of the Swiss cattle population. A dynamic population model can serve as a building block for future disease transmission models and help policy makers in developing strategies regarding animal health, animal welfare, livestock management and productivity. The Swiss cattle population was therefore modelled using a system of ordinary differential equations. The model was stratified by production type (dairy or beef), age and gender (male and female calves: 0-1 year, heifers and young bulls: 1-2 years, cows and bulls: older than 2 years). The simulation of the Swiss cattle population reflects the observed pattern accurately. Parameters were optimized on the basis of the goodness-of-fit (using the Powell algorithm). The fitted rates were compared with calculated rates from the AMD and differed only marginally. This gives confidence in the fitted rates of parameters that are not directly deductible from the AMD (e.g. the proportion of calves that are moved from the dairy system to fattening plants).

Directional statistics: introduction

In many of the natural and physical sciences, measurements are directions, either in two or three dimensions. The analysis of directional data relies on specific statistical models and procedures, which differ from the usual models and methodologies of Cartesian data. This chapter briefly introduces statistical models and inference for this type of data. The basic von Mises-Fisher distribution is introduced and nonparametric methods such as goodness-of-fit tests are presented. Further references are given for exploring related topics such as correlation and regression.