Predictive Factors for Intraocular Pressure Reduction after Phacoemulsification in Swiss Patients.

Background: Phacoemulsification is known to induce postoperative intraocular pressure (IOP) reduction, the degree of which varies according to glaucoma subtype and race. The authors set out to investigate the effect of cataract surgery on IOP, in a Swiss Caucasian population, and identify ocular predictive factors. Patients and Methods: 234 consecutive cases of 188 patients undergoing phacoemulsification between January 2011 and December 2012 were retrospectively reviewed and data collected. Exclusion criteria included acute angle closure, malignant glaucoma and pre-existing or subsequent glaucoma surgery. Pre- and post-operative visual acuity, IOP, gonioscopic findings, glaucoma medications, and laser treatments were recorded for eligible eyes. All eyes received the same postoperative regimen. Using multivariate analysis the predictive power of preoperative IOP, iridocorneal angle width, axial length on IOP reduction following phacoemulsification at months 3, 6 and 12 postoperatively were assessed. Eyes with narrow angles were compared against those with open angles. Results: 172 eyes of 121 patients met the inclusion criteria; mean age was 70.3 years (SD ± 10.7 years), with 77 males. Preoperatively median IOP was 16 mmHg (range 9-32 mmHg), mean number of glaucoma medications was 1.2 (SD ± 1.1), median visual acuity was 0.28 LogMAR (range 0-2.3LogMar). At 3 months post-operatively mean IOP decreased to 14 mmHg (p < 0.01) and remained statistically significantly reduced until 12 months, mean number of glaucoma medications was reduced to 1.0 and mean Snellen visual acuity increased to 0.8. Multivariate analysis revealed that pre-operative IOP and iridocorneal angle width (at 3 months) were significant predictive indicators of IOP reduction. At 12 months, IOP reduction was similar between open and narrow angle groups and total IOP reduction was no longer statistically significant. No intraoperative complications were recorded. Conclusions: Intraocular pressure reduction following phacoemulsification was greatest during the very early post-operative period, particularly in narrow angle patients. By one year, angle size was no longer predictive of IOP lowering, however pre-operative IOP and number of anti-glaucoma medications remained correlated with total IOP reduction.

Establishment and characterization of models of chemotherapy resistance in colorectal cancer: Towards a predictive signature of chemoresistance.

Current standard treatments for metastatic colorectal cancer (CRC) are based on combination regimens with one of the two chemotherapeutic drugs, irinotecan or oxaliplatin. However, drug resistance frequently limits the clinical efficacy of these therapies. In order to gain new insights into mechanisms associated with chemoresistance, and departing from three distinct CRC cell models, we generated a panel of human colorectal cancer cell lines with acquired resistance to either oxaliplatin or irinotecan. We characterized the resistant cell line variants with regards to their drug resistance profile and transcriptome, and matched our results with datasets generated from relevant clinical material to derive putative resistance biomarkers. We found that the chemoresistant cell line variants had distinctive irinotecan- or oxaliplatin-specific resistance profiles, with non-reciprocal cross-resistance. Furthermore, we could identify several new, as well as some previously described, drug resistance-associated genes for each resistant cell line variant. Each chemoresistant cell line variant acquired a unique set of changes that may represent distinct functional subtypes of chemotherapy resistance. In addition, and given the potential implications for selection of subsequent treatment, we also performed an exploratory analysis, in relevant patient cohorts, of the predictive value of each of the specific genes identified in our cellular models.

Minimal requirements for parameters to be used for the development of predictive models for microbial source tracking. The example of the pair somatic coliphages and phages infecting Bacteroides

Several methods and approaches for measuring parameters to determine fecal sources of pollution in water have been developed in recent years. No single microbial or chemical parameter has proved sufficient to determine the source of fecal pollution. Combinations of parameters involving at least one discriminating indicator and one universal fecal indicator offer the most promising solutions for qualitative and quantitative analyses. The universal (nondiscriminating) fecal indicator provides quantitative information regarding the fecal load. The discriminating indicator contributes to the identification of a specific source. The relative values of the parameters derived from both kinds of indicators could provide information regarding the contribution to the total fecal load from each origin. It is also essential that both parameters characteristically persist in the environment for similar periods. Numerical analysis, such as inductive learning methods, could be used to select the most suitable and the lowest number of parameters to develop predictive models. These combinations of parameters provide information on factors affecting the models, such as dilution, specific types of animal source, persistence of microbial tracers, and complex mixtures from different sources. The combined use of the enumeration of somatic coliphages and the enumeration of Bacteroides-phages using different host specific strains (one from humans and another from pigs), both selected using the suggested approach, provides a feasible model for quantitative and qualitative analyses of fecal source identification.

Effect of radar rainfall time resolution on the predictive capability of a distributed hydrologic model

The performance of a hydrologic model depends on the rainfall input data, both spatially and temporally. As the spatial distribution of rainfall exerts a great influence on both runoff volumes and peak flows, the use of a distributed hydrologic model can improve the results in the case of convective rainfall in a basin where the storm area is smaller than the basin area. The aim of this study was to perform a sensitivity analysis of the rainfall time resolution on the results of a distributed hydrologic model in a flash-flood prone basin. Within such a catchment, floods are produced by heavy rainfall events with a large convective component. A second objective of the current paper is the proposal of a methodology that improves the radar rainfall estimation at a higher spatial and temporal resolution. Composite radar data from a network of three C-band radars with 6-min temporal and 2 × 2 km2 spatial resolution were used to feed the RIBS distributed hydrological model. A modification of the Window Probability Matching Method (gauge-adjustment method) was applied to four cases of heavy rainfall to improve the observed rainfall sub-estimation by computing new Z/R relationships for both convective and stratiform reflectivities. An advection correction technique based on the cross-correlation between two consecutive images was introduced to obtain several time resolutions from 1 min to 30 min. The RIBS hydrologic model was calibrated using a probabilistic approach based on a multiobjective methodology for each time resolution. A sensitivity analysis of rainfall time resolution was conducted to find the resolution that best represents the hydrological basin behaviour.

Improved predictive mapping of indoor radon concentrations using ensemble regression trees based on automatic clustering of geological units.

PURPOSE: According to estimations around 230 people die as a result of radon exposure in Switzerland. This public health concern makes reliable indoor radon prediction and mapping methods necessary in order to improve risk communication to the public. The aim of this study was to develop an automated method to classify lithological units according to their radon characteristics and to develop mapping and predictive tools in order to improve local radon prediction. METHOD: About 240 000 indoor radon concentration (IRC) measurements in about 150 000 buildings were available for our analysis. The automated classification of lithological units was based on k-medoids clustering via pair-wise Kolmogorov distances between IRC distributions of lithological units. For IRC mapping and prediction we used random forests and Bayesian additive regression trees (BART). RESULTS: The automated classification groups lithological units well in terms of their IRC characteristics. Especially the IRC differences in metamorphic rocks like gneiss are well revealed by this method. The maps produced by random forests soundly represent the regional difference of IRCs in Switzerland and improve the spatial detail compared to existing approaches. We could explain 33% of the variations in IRC data with random forests. Additionally, the influence of a variable evaluated by random forests shows that building characteristics are less important predictors for IRCs than spatial/geological influences. BART could explain 29% of IRC variability and produced maps that indicate the prediction uncertainty. CONCLUSION: Ensemble regression trees are a powerful tool to model and understand the multidimensional influences on IRCs. Automatic clustering of lithological units complements this method by facilitating the interpretation of radon properties of rock types. This study provides an important element for radon risk communication. Future approaches should consider taking into account further variables like soil gas radon measurements as well as more detailed geological information.

The predictive value of preoperative B-type natriuretic peptide in children undergoing cardiac surgery

Introduction: B-type natriuretic peptide (BNP) is a biomarker of myocardial stress. In children, the value of preoperative BNP on postoperative outcome is unclear. The aim of this study was to determine the predictive value of preoperative NT-proBNP on postoperative outcome in children after congenital heart surgery. Results: Ninety-seven patients were included in the study with a median age of 3.3 years [0.7-5.2]. Preoperative median NT-proBNP was 412 pg/ml [164-1309]. NT-proBNP was above the P95 reference value for age in 56 patients (58%). Preoperative NT-proBNP was significantly higher in patients who had mechanical ventilation duration of more than 2 days (1156 pg/ml [281-1951] vs. 267 pg/ml [136-790], p=0.003) and who stayed more than 6 days in the pediatric intensive care unit (727 pg/ml [203-1951] vs. 256 pg/ml [136-790], p=0.007). However, preoperative NT-proBNP was not significantly higher in patients with an increased inotropic score, a prolonged cardiopulmonary bypass time or an increased surgical risk category. Conclusions: An elevated preoperative NT-proBNP reflects hemodynamic status and cardiac dysfunction, and therefore is a valuable adjunct in predicting a complicated postoperative course. ___________________________________ Introduction: Le peptide natriurétique type B (BNP) est un marqueur reflétant le stress myocardique. Dans la population pédiatrique, la signification des valeurs préopératoire de BNP, en particulier sur l'évolution postopératoire, n'est pas clairement établie. Le but de l'étude est de déterminer la valeur prédictive de la partie NT sérique du BNP (NT-proBNP) sur l'évolution post opératoire d'enfants porteur d'une cardiopathie congénitale et ayant eu une chirurgie cardiaque. Résultats: Nonante-sept enfants ont été inclus dans l'étude, avec un âge médian de 3.3 ans [0.7-5.2]. La valeur médiane du NT-proBNP préopératoire était de 412 pg/ml [164-1309]. Le NT-proBNP préopératoire était supérieur au P95 des valeurs de référence pour l'âge chez 56 patients (58%). Le NT-proBNP préopératoire était significativement plus élevé chez les patients ayant eu plus de deux jours de ventilation mécanique dans la période postopératoire (1156 pg/ml [281-1951] vs. 267 pg/ml [136-790], p=0.003) et ayant été hospitalisés plus de 6 jours dans l'unité de soins intensifs pédiatrique (727 pg/ml [203-1951] vs. 256 pg/ml [136-790], p=0.007). Par contre, le NT-proBNP préopératoire n'était pas significativement plus élevé chez les patients ayant eu un score d'inotrope élevé pendant leur hospitalisation aux soins intensifs, un temps de circulation extracorporelle prolongé ou ayant subi une chirurgie avec un risque chirurgical élevé. Conclusions: Un NT-proBNP sérique élevé en préopératoire reflète l'importance du stress myocardique induit par l'hémodynamique et la dysfonction myocardique, il est un marqueur qui permet d'améliorer l'identification des patients à risque d'avoir une évolution post opératoire compliquée.

Predictive ability of heel quantitative ultrasound for incident fractures: an individual-level meta-analysis.

UNLABELLED: The relationship between bone quantitative ultrasound (QUS) and fracture risk was estimated in an individual level data meta-analysis of 9 prospective studies of 46,124 individuals and 3018 incident fractures. Low QUS is associated with an increase in fracture risk, including hip fracture. The association with osteoporotic fracture decreases with time. INTRODUCTION: The aim of this meta-analysis was to investigate the association between parameters of QUS and risk of fracture. METHODS: In an individual-level analysis, we studied participants in nine prospective cohorts from Asia, Europe and North America. Heel broadband ultrasonic attenuation (BUA dB/MHz) and speed of sound (SOS m/s) were measured at baseline. Fractures during follow-up were collected by self-report and in some cohorts confirmed by radiography. An extension of Poisson regression was used to examine the gradient of risk (GR, hazard ratio per 1 SD decrease) between QUS and fracture risk adjusted for age and time since baseline in each cohort. Interactions between QUS and age and time since baseline were explored. RESULTS: Baseline measurements were available in 46,124 men and women, mean age 70 years (range 20-100). Three thousand and eighteen osteoporotic fractures (787 hip fractures) occurred during follow-up of 214,000 person-years. The summary GR for osteoporotic fracture was similar for both BUA (1.45, 95 % confidence intervals (CI) 1.40-1.51) and SOS (1.42, 95 % CI 1.36-1.47). For hip fracture, the respective GRs were 1.69 (95 % CI, 1.56-1.82) and 1.60 (95 % CI, 1.48-1.72). However, the GR was significantly higher for both fracture outcomes at lower baseline BUA and SOS (p < 0.001). The predictive value of QUS was the same for men and women and for all ages (p > 0.20), but the predictive value of both BUA and SOS for osteoporotic fracture decreased with time (p = 0.018 and p = 0.010, respectively). For example, the GR of BUA for osteoporotic fracture, adjusted for age, was 1.51 (95 % CI 1.42-1.61) at 1 year after baseline, but at 5 years, it was 1.36 (95 % CI 1.27-1.46). CONCLUSIONS: Our results confirm that quantitative ultrasound is an independent predictor of fracture for men and women particularly at low QUS values.

CBS: an open platform that integrates predictive methods and epigenetics information to characterize conserved regulatory features in multiple Drosophila genomes.

Background: Information about the composition of regulatory regions is of great value for designing experiments to functionally characterize gene expression. The multiplicity of available applications to predict transcription factor binding sites in a particular locus contrasts with the substantial computational expertise that is demanded to manipulate them, which may constitute a potential barrier for the experimental community. Results: CBS (Conserved regulatory Binding Sites, http://compfly.bio.ub.es/CBS) is a public platform of evolutionarily conserved binding sites and enhancers predicted in multiple Drosophila genomes that is furnished with published chromatin signatures associated to transcriptionally active regions and other experimental sources of information. The rapid access to this novel body of knowledge through a user-friendly web interface enables non-expert users to identify the binding sequences available for any particular gene, transcription factor, or genome region. Conclusions: The CBS platform is a powerful resource that provides tools for data mining individual sequences and groups of co-expressed genes with epigenomics information to conduct regulatory screenings in Drosophila.

Duration of untreated psychosis: Impact of the definition of treatment onset on its predictive value over three years of treatment.

BACKGROUND: While reduction of DUP (Duration of Untreated Psychosis) is a key goal in early intervention strategies, the predictive value of DUP on outcome has been questioned. We planned this study in order to explore the impact of three different definition of "treatment initiation" on the predictive value of DUP on outcome in an early psychosis sample. METHODS: 221 early psychosis patients aged 18-35 were followed-up prospectively over 36 months. DUP was measured using three definitions for treatment onset: Initiation of antipsychotic medication (DUP1); engagement in a specialized programme (DUP2) and combination of engagement in a specialized programme and adherence to medication (DUP3). RESULTS: 10% of patients never reached criteria for DUP3 and therefore were never adequately treated over the 36-month period of care. While DUP1 and DUP2 had a limited predictive value on outcome, DUP3, based on a more restrictive definition for treatment onset, was a better predictor of positive and negative symptoms, as well as functional outcome at 12, 24 and 36 months. Globally, DUP3 explained 2 to 5 times more of the variance than DUP1 and DUP2, with effect sizes falling in the medium range according to Cohen. CONCLUSIONS: The limited predictive value of DUP on outcome in previous studies may be linked to problems of definitions that do not take adherence to treatment into account. While they need replication, our results suggest effort to reduce DUP should continue and aim both at early detection and development of engagement strategies.

Positive predictive values of Breast Imaging Reporting and Data System (BI-RADS®) categories 3, 4 and 5 in breast lesions submitted to percutaneous biopsy

Objective To evaluate the BI-RADS as a predictive factor of suspicion for malignancy in breast lesions by correlating radiological with histological results and calculating the positive predictive value for categories 3, 4 and 5 in a breast cancer reference center in the city of São Paulo. Materials and Methods Retrospective, analytical and cross-sectional study including 725 patients with mammographic and/or sonographic findings classified as BI-RADS categories 3, 4 and 5 who were referred to the authors' institution to undergo percutaneous biopsy. The tests results were reviewed and the positive predictive value was calculated by means of a specific mathematical equation. Results Positive predictive values found for categories 3, 4 and 5 were respectively the following: 0.74%, 33.08% and 92.95%, for cases submitted to ultrasound-guided biopsy, and 0.00%, 14.90% and 100% for cases submitted to stereotactic biopsy. Conclusion The present study demonstrated high suspicion for malignancy in lesions classified as category 5 and low risk for category 3. As regards category 4, the need for systematic biopsies was observed.

DNA Topoisomerase I Gene Copy Number and mRNA Expression Assessed as Predictive Biomarkers for Adjuvant Irinotecan in Stage II/III Colon Cancer.

PURPOSE: Prospective-retrospective assessment of theTOP1gene copy number andTOP1mRNA expression as predictive biomarkers for adjuvant irinotecan in stage II/III colon cancer. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tissue microarrays were obtained from an adjuvant colon cancer trial (PETACC3) where patients were randomized to 5-fluorouracil/folinic acid with or without additional irinotecan.TOP1copy number status was analyzed by fluorescencein situhybridization (FISH) using aTOP1/CEN20 dual-probe combination.TOP1mRNA data were available from previous analyses. RESULTS: TOP1FISH and follow-up data were obtained from 534 patients.TOP1gain was identified in 27% using a single-probe enumeration strategy (≥4TOP1signals per cell) and in 31% when defined by aTOP1/CEN20 ratio ≥ 1.5. The effect of additional irinotecan was not dependent onTOP1FISH status.TOP1mRNA data were available from 580 patients with stage III disease. Benefit of irinotecan was restricted to patients characterized byTOP1mRNA expression ≥ third quartile (RFS: HRadjusted, 0.59;P= 0.09; OS: HRadjusted, 0.44;P= 0.03). The treatment byTOP1mRNA interaction was not statistically significant, but in exploratory multivariable fractional polynomial interaction analysis, increasingTOP1mRNA values appeared to be associated with increasing benefit of irinotecan. CONCLUSIONS: In contrast to theTOP1copy number, a trend was demonstrated for a predictive property ofTOP1mRNA expression. On the basis ofTOP1mRNA, it might be possible to identify a subgroup of patients where an irinotecan doublet is a clinically relevant option in the adjuvant setting of colon cancer.Clin Cancer Res; 22(7); 1621-31. ©2015 AACR.

First trimester maternal level of PAPP-A, βhCG and ethnicity as predictive of Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) is one of the leading causes of perinatal mortality and morbidity. Nowadays, this condition is detected in the 3rt and last trimester of gestation when the pathology is already established and success of therapeutic strategies are limited. As the physiopathology of the disease suggests that the problem stems from poor placental implantation, it would be quite advantageous to identify women at increased risk in the first or second trimester of gestation because it then might be possible to offer treatment interventions or at least to establish increased surveillance for high risk pregnancies. Maternal levels of pregnancy-associated plasma protein-A (PAPP-A) and free β human chorionic gonadotropin (free βhCG) has been shown to be effective in first trimester screening for chromosomal abnormalities, primarily trisomies 21, 13 and 18. Previous studies evaluating PAPP-A and free βhCG measured in the first trimester in relation with IUGR have provided conflicting results. Moreover, it has been suggested that black ethnicity is another important predictive factor for fetal growth restriction.Objective: To analyse the association between first trimester serum analytes (PAPP-A and free βhCG) and ethnicity with Intrauterine Growth Restriction.Methods: The study consists in a retrospective cohort, including all singleton pregnancies with complete outcome data that had undergone first trimester screening (PAPP-A and free βhCG) at 11-13+6weeks of gestation between 1/1/2010 - 31/12/2012 in Hospital Universitari Dr Josep Trueta. Biochemical markers are converted to multiples of the median (MoMs) and percentiles 5 and 10 are calculated. The association between free βhCG and PAPP-A with the incidence of IUGR is evaluated in combination with maternal ethnicity. Bivariate and logistic regression analyses are performed to adjust this association for co variables