OMIP contribution to CMIP6: experimental and diagnostic protocol for the physical component of the Ocean Model Intercomparison Project

The Ocean Model Intercomparison Project (OMIP) is an endorsed project in the Coupled Model Intercomparison Project Phase 6 (CMIP6). OMIP addresses CMIP6 science questions, investigating the origins and consequences of systematic model biases. It does so by providing a framework for evaluating (including assessment of systematic biases), understanding, and improving ocean, sea-ice, tracer, and biogeochemical components of climate and earth system models contributing to CMIP6. Among the WCRP Grand Challenges in climate science (GCs), OMIP primarily contributes to the regional sea level change and near-term (climate/decadal) prediction GCs. OMIP provides (a) an experimental protocol for global ocean/sea-ice models run with a prescribed atmospheric forcing; and (b) a protocol for ocean diagnostics to be saved as part of CMIP6. We focus here on the physical component of OMIP, with a companion paper (Orr et al., 2016) detailing methods for the inert chemistry and interactive biogeochemistry. The physical portion of the OMIP experimental protocol follows the interannual Coordinated Ocean-ice Reference Experiments (CORE-II). Since 2009, CORE-I (Normal Year Forcing) and CORE-II (Interannual Forcing) have become the standard methods to evaluate global ocean/sea-ice simulations and to examine mechanisms for forced ocean climate variability. The OMIP diagnostic protocol is relevant for any ocean model component of CMIP6, including the DECK (Diagnostic, Evaluation and Characterization of Klima experiments), historical simulations, FAFMIP (Flux Anomaly Forced MIP), C4MIP (Coupled Carbon Cycle Climate MIP), DAMIP (Detection and Attribution MIP), DCPP (Decadal Climate Prediction Project), ScenarioMIP, HighResMIP (High Resolution MIP), as well as the ocean/sea-ice OMIP simulations.

ArrayMining: a modular web-application for microarray analysis combining ensemble and consensus methods with cross-study normalization

Background: Statistical analysis of DNA microarray data provides a valuable diagnostic tool for the investigation of genetic components of diseases. To take advantage of the multitude of available data sets and analysis methods, it is desirable to combine both different algorithms and data from different studies. Applying ensemble learning, consensus clustering and cross-study normalization methods for this purpose in an almost fully automated process and linking different analysis modules together under a single interface would simplify many microarray analysis tasks. Results: We present ArrayMining.net, a web-application for microarray analysis that provides easy access to a wide choice of feature selection, clustering, prediction, gene set analysis and cross-study normalization methods. In contrast to other microarray-related web-tools, multiple algorithms and data sets for an analysis task can be combined using ensemble feature selection, ensemble prediction, consensus clustering and cross-platform data integration. By interlinking different analysis tools in a modular fashion, new exploratory routes become available, e.g. ensemble sample classification using features obtained from a gene set analysis and data from multiple studies. The analysis is further simplified by automatic parameter selection mechanisms and linkage to web tools and databases for functional annotation and literature mining. Conclusion: ArrayMining.net is a free web-application for microarray analysis combining a broad choice of algorithms based on ensemble and consensus methods, using automatic parameter selection and integration with annotation databases.

Characteristics of Clostridium difficile infection in patients with discordant diagnostic test results

Background: Clinical features of Clostridium difficile infection (CDI) cases diagnosed by detection of polymerase chain reaction (PCR), with negative toxin enzyme immunoassay results (EIA) have not been fully elucidated. The purpose of this study was to determine the magnitude of CDI patients who had negative EIA toxin determinations but positive PCR tests, and their differences in clinical presentation. Methods: We performed a retrospective study comparing the clinical features of CDI cases detected by EIA (toxins A + B) with cases detected by PCR (toxin negative, PCR positive) over a 16-month period. Only patients with an initial Clostridium difficile infection episode that fulfilled a standardized definition were included. Results: During the study period, 107 episodes of CDI were detected. Seventy-four patients (69%) had positive glutamate dehydrogenase (GDH) antigen and EIA determinations (EIA positive patients). Thirty-three patients (31%) had GDH positive, negative toxin EIA and positive PCR determination (PCR positive patients). PCR positive patients were younger, 57 (27) years (mean [SD]), than EIA positive patients, 71 (16) years, (p < 0.001). Fewer PCR positive patients were receiving proton pump inhibitors (21 patients, 64%) than EIA positive patients (61 patients, 82%, p = 0.034). The clinical presentation was similar in both groups. In the multivariate analysis, lower age was identified as the only independent variable associated with PCR positive patients. Conclusions: One third of Clostridium difficile infection patients present negative toxin EIA and PCR positive tests. Performing PCR determination after the negative EIA test is more relevant in younger patients.

Evaluation of faecal sampling methods for the analysis of Giardia sp. in companion animals

Dissertação de Mestrado Integrado em Medicina Veterinária

Th1/Th2 Cytokine Profile and Its Diagnostic Value in Mycoplasma pneumoniae Pneumonia

Background: The levels of Th1/Th2 cytokine can alter in pathogenic infection in children with pneumonia. Objectives: To evaluate Th1/Th2 cytokine profile and its diagnostic value in M. pneumoniae pneumonia in children. Patients and Methods: Children with M. pneumoniae mono-infection and 30 healthy children were tested with cytokines assay. We used real time PCR to detect M. pneumoniae in children with pneumonia. Results: M. pneumoniae test was positive in 2188 (16.62%) out of 13161 pneumonia children. Children aged 5 - 9 years had the highest rate and summer was a season with high rate of M. pneumoniae incidence in Zhejiang province. During the course of study, in 526 pneumonia children with M. pneumoniae mono-infection and 30 healthy children cytokines assay was performed. IL-2 level of M. pneumoniae pneumonia children was lower than that of healthy children (median levels, pg/mL: IL-2: 3.2 vs. 5.7, P = 0.00), while IL-4, IL-10 and IFN-γ were higher than in healthy children (median levels, pg/mL: IL-4: 3.2 vs. 1.5, P = 0.00; IL-10: 5.6 vs. 2.5, P = 0.001; IFN-γ: 20.4 vs. 4.8, P = 0.001). Conclusions: IL-2 decreases and IL-4, IL-10 and IFN-γ increase in children with M. pneumoniae pneumonia, which has a promising prospect in diagnosis of this disease in clinical practice.

Genetic diversity of Mycobacterium avium isolates recovered from clinical samples and from the environment: molecular characterization for diagnostic purposes

Isolation of Mycobacterium avium complex (MAC) organisms from clinical samples may occur in patients without clinical disease, making the interpretation of results difficult. The clinical relevance of MAC isolates from different types of clinical samples (n = 47) from 39 patients in different sections of a hospital was assessed by comparison with environmental isolates (n = 17) from the hospital. Various methods for identification and typing (commercial probes, phenotypic characteristics, PCR for detection of IS1245 and IS901, sequencing of the hsp65 gene, and pulsed-field gel electrophoresis) were evaluated. The same strain was found in all the environmental isolates, 21 out of 23 (91.3%) of the isolates cultured from urine samples, and 5 out of 19 (26.3%) isolates from respiratory specimens. This strain did not cause disease in the patients. Testing best characterized the strain as M. avium subsp. hominissuis, with the unusual feature that 81.4% of these isolates lacked the IS1245 element. Contamination of certain clinical samples with an environmental strain was the most likely event; therefore, characterization of the environmental mycobacteria present in health care facilities should be performed to discard false-positive isolations in nonsterile samples, mainly urine samples. Molecular techniques applied in this study demonstrated their usefulness for this purpose.

A Diagnostic Calculator for Detecting Glaucoma on the Basis of Retinal Nerve Fiber Layer, Optic Disc, and Retinal Ganglion Cell Analysis by Optical Coherence Tomography

Purpose: The purpose of this study was to develop and validate a multivariate predictive model to detect glaucoma by using a combination of retinal nerve fiber layer (RNFL), retinal ganglion cell-inner plexiform (GCIPL), and optic disc parameters measured using spectral-domain optical coherence tomography (OCT). Methods: Five hundred eyes from 500 participants and 187 eyes of another 187 participants were included in the study and validation groups, respectively. Patients with glaucoma were classified in five groups based on visual field damage. Sensitivity and specificity of all glaucoma OCT parameters were analyzed. Receiver operating characteristic curves (ROC) and areas under the ROC (AUC) were compared. Three predictive multivariate models (quantitative, qualitative, and combined) that used a combination of the best OCT parameters were constructed. A diagnostic calculator was created using the combined multivariate model. Results: The best AUC parameters were: inferior RNFL, average RNFL, vertical cup/disc ratio, minimal GCIPL, and inferior-temporal GCIPL. Comparisons among the parameters did not show that the GCIPL parameters were better than those of the RNFL in early and advanced glaucoma. The highest AUC was in the combined predictive model (0.937; 95% confidence interval, 0.911–0.957) and was significantly (P = 0.0001) higher than the other isolated parameters considered in early and advanced glaucoma. The validation group displayed similar results to those of the study group. Conclusions: Best GCIPL, RNFL, and optic disc parameters showed a similar ability to detect glaucoma. The combined predictive formula improved the glaucoma detection compared to the best isolated parameters evaluated. The diagnostic calculator obtained good classification from participants in both the study and validation groups.

Psychometric properties of the Iranian version of the premature ejaculation diagnostic tool

Introduction Premature ejaculation (PE) is one of the most prevalent male sexual problems. The Premature Ejaculation Diagnostic Tool (PEDT) is a suitable patient-reported outcome measure for the assessment of PE. Aim To examine the psychometric proporties of a translated and culturally adapted version of the PEDT in a sample of Iranian men suffering from PE. Methods Two independent samples were compared, one including patients with PE based on the DSM-IV-TR criteria (n = 269) and the other including healthy men without PE (n = 289). A backward–forward translation procedure was used to translate the PEDT into Persian. Both samples were asked to fill in the PEDT twice—at baseline and 4 weeks later. Main Outcome Measures Internal consistency, test–retest reliability, convergent validity, factor structure, measurement invariance across sexual health status (i.e., between men with and without PE). Results Mean ages of men without and with PE were 34.9 and 35.3 years, respectively. Cronbach's alpha coefficient for the total PEDT score was 0.89. All items and the total score were remarkably consistent between the two measurement points. All five PEDT items correlated at r = 0.40 or greater with their own scale, indicating good convergent validity. There was a high and significant correlation (r = −0.82, P  < 0.001) between the PEDT score and IELT. Healthy men reported lower scores (fewer complaints) on the PEDT compared with the PE group. A single-factor model was found to be best-fitting in the exploratory factor analysis; this was confirmed by confirmatory factor analysis. The PEDT was invariant across sexual health status and perceived similarly by men with and without PE. Conclusion The results provide evidence for good reliability and validity of the Iranian version of the PEDT. The questionnaire therefore represents a suitable tool for screening PE in Iranian men.

Utility and safety of invasive (fractional flow reserve) and non-invasive (cardiac magnetic resonance imaging) diagnostic tests in patients with NSTEMI

A prospective randomised controlled clinical trial of treatment decisions informed by invasive functional testing of coronary artery disease severity compared with standard angiography-guided management was implemented in 350 patients with a recent non-ST elevation myocardial infarction (NSTEMI) admitted to 6 hospitals in the National Health Service. The main aims of this study were to examine the utility of both invasive fractional flow reserve (FFR) and non-invasive cardiac magnetic resonance imaging (MRI) amongst patients with a recent diagnosis of NSTEMI. In summary, the findings of this thesis are: (1) the use of FFR combined with intravenous adenosine was feasible and safe amongst patients with NSTEMI and has clinical utility; (2) there was discordance between the visual, angiographic estimation of lesion significance and FFR; (3). The use of FFR led to changes in treatment strategy and an increase in prescription of medical therapy in the short term compared with an angiographically guided strategy; (4) in the incidence of major adverse cardiac events (MACE) at 12 months follow up was similar in the two groups. Cardiac MRI was used in a subset of patients enrolled in two hospitals in the West of Scotland. T1 and T2 mapping methods were used to delineate territories of acute myocardial injury. T1 and T2 mapping were superior when compared with conventional T2-weighted dark blood imaging for estimation of the ischaemic area-at-risk (AAR) with less artifact in NSTEMI. There was poor correlation between the angiographic AAR and MRI methods of AAR estimation in patients with NSTEMI. FFR had a high accuracy at predicting inducible perfusion defects demonstrated on stress perfusion MRI. This thesis describes the largest randomized trial published to date specifically looking at the clinical utility of FFR in the NSTEMI population. We have provided evidence of the diagnostic and clinical utility of FFR in this group of patients and provide evidence to inform larger studies. This thesis also describes the largest ever MRI cohort, including with myocardial stress perfusion assessments, specifically looking at the NSTEMI population. We have demonstrated the diagnostic accuracy of FFR to predict reversible ischaemia as referenced to a non-invasive gold standard with MRI. This thesis has also shown the futility of using dark blood oedema imaging amongst all comer NSTEMI patients when compared to novel T1 and T2 mapping methods.

A complexity-based diagnostic on the democratic unity roundtable mud: problems and alternatives (2008-2016)

Este trabajo exploratorio estudia al movimiento político Mesa de la Unidad Democrática (MUD), creada con el fin de oponerse la Gobierno socialista existente en venezuela. La crítica que este documento realiza, parte desde el punto de vista de la Ciencia de la Complejidad. Algunos conceptos clave de sistemas complejos han sido utilizados para explicar el funcionamiento y organización de la MUD, esto con el objetivo de generar un diagnóstico integral de los problemas que enfrenta, y evidenciar las nuevas percepciones sobre comportamientos perjudiciales que el partido tiene actualmente. Con el enfoque de la complejidad se pretende ayudar a comprender mejor el contexto que enmarca al partido y, para, finalmente aportar una serie de soluciones a los problemas de cohesión que presen

Methods for Biodata Analysis in different Omic Contexts

The world of Computational Biology and Bioinformatics presently integrates many different expertise, including computer science and electronic engineering. A major aim in Data Science is the development and tuning of specific computational approaches to interpret the complexity of Biology. Molecular biologists and medical doctors heavily rely on an interdisciplinary expert capable of understanding the biological background to apply algorithms for finding optimal solutions to their problems. With this problem-solving orientation, I was involved in two basic research fields: Cancer Genomics and Enzyme Proteomics. For this reason, what I developed and implemented can be considered a general effort to help data analysis both in Cancer Genomics and in Enzyme Proteomics, focusing on enzymes which catalyse all the biochemical reactions in cells. Specifically, as to Cancer Genomics I contributed to the characterization of intratumoral immune microenvironment in gastrointestinal stromal tumours (GISTs) correlating immune cell population levels with tumour subtypes. I was involved in the setup of strategies for the evaluation and standardization of different approaches for fusion transcript detection in sarcomas that can be applied in routine diagnostic. This was part of a coordinated effort of the Sarcoma working group of "Alleanza Contro il Cancro". As to Enzyme Proteomics, I generated a derived database collecting all the human proteins and enzymes which are known to be associated to genetic disease. I curated the data search in freely available databases such as PDB, UniProt, Humsavar, Clinvar and I was responsible of searching, updating, and handling the information content, and computing statistics. I also developed a web server, BENZ, which allows researchers to annotate an enzyme sequence with the corresponding Enzyme Commission number, the important feature fully describing the catalysed reaction. More to this, I greatly contributed to the characterization of the enzyme-genetic disease association, for a better classification of the metabolic genetic diseases.

Advancing Bag-of-visual-words Representations For Lesion Classification In Retinal Images.

Diabetic Retinopathy (DR) is a complication of diabetes that can lead to blindness if not readily discovered. Automated screening algorithms have the potential to improve identification of patients who need further medical attention. However, the identification of lesions must be accurate to be useful for clinical application. The bag-of-visual-words (BoVW) algorithm employs a maximum-margin classifier in a flexible framework that is able to detect the most common DR-related lesions such as microaneurysms, cotton-wool spots and hard exudates. BoVW allows to bypass the need for pre- and post-processing of the retinographic images, as well as the need of specific ad hoc techniques for identification of each type of lesion. An extensive evaluation of the BoVW model, using three large retinograph datasets (DR1, DR2 and Messidor) with different resolution and collected by different healthcare personnel, was performed. The results demonstrate that the BoVW classification approach can identify different lesions within an image without having to utilize different algorithms for each lesion reducing processing time and providing a more flexible diagnostic system. Our BoVW scheme is based on sparse low-level feature detection with a Speeded-Up Robust Features (SURF) local descriptor, and mid-level features based on semi-soft coding with max pooling. The best BoVW representation for retinal image classification was an area under the receiver operating characteristic curve (AUC-ROC) of 97.8% (exudates) and 93.5% (red lesions), applying a cross-dataset validation protocol. To assess the accuracy for detecting cases that require referral within one year, the sparse extraction technique associated with semi-soft coding and max pooling obtained an AUC of 94.2 ± 2.0%, outperforming current methods. Those results indicate that, for retinal image classification tasks in clinical practice, BoVW is equal and, in some instances, surpasses results obtained using dense detection (widely believed to be the best choice in many vision problems) for the low-level descriptors.

Evaluation Of Different Treatment Methods Against Denture Stomatitis: A Randomized Clinical Study.

The aim of this clinical study was to determine the efficacy of Uncaria tomentosa (cat's claw) against denture stomatitis (DS). Fifty patients with DS were randomly assigned into 3 groups to receive 2% miconazole, placebo, or 2% U tomentosa gel. DS level was recorded immediately, after 1 week of treatment, and 1 week after treatment. The clinical effectiveness of each treatment was measured using Newton's criteria. Mycologic samples from palatal mucosa and prosthesis were obtained to determinate colony forming units per milliliter (CFU/mL) and fungal identification at each evaluation period. Candida species were identified with HiCrome Candida and API 20C AUX biochemical test. DS severity decreased in all groups (P < .05). A significant reduction in number of CFU/mL after 1 week (P < .05) was observed for all groups and remained after 14 days (P > .05). C albicans was the most prevalent microorganism before treatment, followed by C tropicalis, C glabrata, and C krusei, regardless of the group and time evaluated. U tomentosa gel had the same effect as 2% miconazole gel. U tomentosa gel is an effective topical adjuvant treatment for denture stomatitis.

High Diagnostic Accuracy And Reproducibility Of Fine-needle Aspiration Cytology For Diagnosing Salivary Gland Tumors: Cytohistologic Correlation In 182 Cases.

The purpose of this study was to assess the efficacy and reproducibility of the cytologic diagnosis of salivary gland tumors (SGTs) using fine-needle aspiration cytology (FNAC). The study aimed to determine diagnostic accuracy, sensitivity, and specificity and to evaluate the extent of interobserver agreement. We retrospectively evaluated SGTs from the files of the Division of Pathology at the Clinics Hospital of São Paulo and Piracicaba Dental School between 2000 and 2006. We performed cytohistologic correlation in 182 SGTs. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 94%, 100%, 100%, 100%, and 99%, respectively. The interobserver cytologic reproducibility showed significant statistical concordance (P < .0001). FNAC is an effective tool for performing a reliable preoperative diagnosis in SGTs and shows high diagnostic accuracy and consistent interobserver reproducibility. Further FNAC studies analyzing large samples of malignant SGTs and reactive salivary lesions are needed to confirm their accuracy.

Newborn Hearing Screening And Early Diagnostic In The Nicu.

The aim was to describe the outcome of neonatal hearing screening (NHS) and audiological diagnosis in neonates in the NICU. The sample was divided into Group I: neonates who underwent NHS in one step and Group II: neonates who underwent a test and retest NHS. NHS procedure was automated auditory brainstem response. NHS was performed in 82.1% of surviving neonates. For GI, referral rate was 18.6% and false-positive was 62.2% (normal hearing in the diagnostic stage). In GII, with retest, referral rate dropped to 4.1% and false-positive to 12.5%. Sensorineural hearing loss was found in 13.2% of infants and conductive in 26.4% of cases. There was one case of auditory neuropathy spectrum (1.9%). Dropout rate in whole process was 21.7% for GI and 24.03% for GII. We concluded that it was not possible to perform universal NHS in the studied sample or, in many cases, to apply it within the first month of life. Retest reduced failure and false-positive rate and did not increase evasion, indicating that it is a recommendable step in NHS programs in the NICU. The incidence of hearing loss was 2.9%, considering sensorineural hearing loss (0.91%), conductive (1.83%) and auditory neuropathy spectrum (0.19%).