Predictive Value In Relation Research Articles

The prevalence and predictive value of the SLC30A8 R325W polymorphism and zinc transporter 8 autoantibodies in the development of GDM and postpartum type 1 diabetes.

The objectives were to evaluate possible associations between the SLC30A8 R325W polymorphism and gestational diabetes mellitus (GDM) as well as postpartum development of type 2 diabetes. Furthermore, we wanted to confirm the prevalence of zinc transporter 8 autoantibodies (ZnT8A), as previously reported, in a larger population and study its predictive value in relation to other βcell specific autoantibodies in postpartum development of type 1 diabetes. Women diagnosed with GDM (n=776) and women without diabetes (n=511) were included in the study. Autoantibodies were analyzed in all women using enzyme-linked immunosorbent assay. DNA was extracted when possible from women with GDM (n=536) and all of the controls. R325W was detected through polymerase chain reaction and specific restriction digestion. The R325W C-allele were more frequent in women with GDM compared to in controls (OR 1.47, 95% CI 1.16-1.88, p=0.0018) but not significantly increased in women with GDM and postpartum development of type 2 diabetes. Autoantibodies were found in 6.8% (53/776) of the women with GDM and approximately 3.2% (25/776) were ZnT8A positive. Approximately 19% (10/53) of the autoantibody positive women with GDM developed postpartum type 1 diabetes. In conclusion, this is the first study to report a significant association between the R325W C-allele and increased risk of developing GDM. All of the autoantibody positive women with GDM who developed postpartum type 1 diabetes were positive for autoantibodies against glutamic acid decarboxylase (GADA). Thus ZnT8A did not have any additional predictive value in postpartum development of type 1 diabetes.

Temperature as a predictor of fouling and diarrhea in slaughter pigs

The PigIT Project aims at improving welfare and productivity of slaughter pigs by integration of various sensor systems for alarm purposes. Here we present an exploratory analysis to assess the predictive value of temperature sensor data with respect to pen fouling and diarrhea. We recorded the temperature at two locations in 8 pens between November 2013 and December 2014. A single logistic regression model was made to express the probability of either diarrhea or fouling per pen per day, and was reduced via backwards elimination. The predictive performances were evaluated by the area under the receiver operating characteristics curve (AUC). Indiscriminant prediction of either event reached an AUC of 0.80. Similar performances were seen when predicting each of the events on their own using the same model, with AUC values at 0.78 and 0.81 for diarrhea and fouling, respectively. Thus, temperature information seems to provide predictive value in relation to fouling and diarrhea. It would be meaningful to combine this information with other available data by using more advanced models to achieve an optimal predictive power.

Perceived motivational team climate in relation to task and social cohesion among male college athletes

The purpose of the study was to examine the relationship between perceptions of the motivational team climate and task and social cohesion among male college athletes. Basketball and soccer players (n = 179) completed two response measures, the Perceived Motivational Climate in Sport Questionnaire-II (Newton, Duda, & Yin) and the Group Environment Questionnaire (GEQ; Carron, Widmeyer, & Brawley) before practice in a team setting near the end of the competitive season. Hierarchical linear modeling analysis revealed that individual perceptions of a task-involving climate positively predicted, and perceptions of an ego-involving climate negatively predicted, individual-attraction-to-group task cohesion. Further analysis indicated that perceptions of a task-involving climate also significantly predicted individual-attraction-to-group social cohesion and group-integration task cohesion. Perceptions of an ego-involving climate failed to demonstrate any other predictive value in relation to team cohesion. Discussion underscores the beneficial nature of a task-involving motivational team climate in regard to the formation and development of task and social cohesion among competitive male college athletes.

Use of enzyme linked immunospot assay (ELISpot) for monitoring treatment response of pulmonary tuberculosis patients

BackgroundTuberculosis (TB) remains one of the major causes of death from a single infectious agent worldwide. The rapid emergence of drug resistant mycobacteria has strengthened the demand for rapid methods for detection of mycobacteria in clinical samples. As prevention of tuberculosis relies on the early detection and cure of the infectious cases, current efforts are focused upon improving the rapidity of identification of Mycobacterium tuberculosis, allowing prompt initiation of appropriate therapy. The rapid enzyme linked immunospot assay (ELISpot) method was developed in the late 1990s based on the numbers of spots made by interferon gamma producing T cells stimulated by culture filtrate protein-10 (CFP-10) or early secretory antigenic target-6 (ESAT-6). Therefore, a T-cell response to these antigens could in theory serve as a specific marker of M. tuberculosis infection.Aim of the workIs to assess the potential utility of ELISpot assay for monitoring treatment response of pulmonary tuberculosis patients.Patients and methodsThe study was done on 30 patients diagnosed as pulmonary tuberculosis on clinical, radiological and bacteriological bases. They were collected from Zagazig Chest Hospital and Zagazig University Hospitals from January 2010 to January 2011. A total of 15 healthy volunteers were enrolled in this study as control subjects. The following were performed for all patients before treatment initiation: full history taking, complete clinical examination, chest X-ray, postero-anterior and lateral views, tuberculin skin test (TST) by Mantoux technique, and routine laboratory investigations. Three successive sputum samples for sputum smear Ziehl–Neelsen (Z–N) staining and sputum collection for Mycobacterium culture on Lowenstein–Jensen media (L.J. media) were done. Collection of 2ml heparinized blood for enzyme linked immunospot assay (ELISpot) was done. All patients received four antituberculous drugs, isoniazid, rifampicin, pyrazinamide and ethambutol, for the initial 2months. After 2months of therapy; another three successive sputum samples for sputum smear Ziehl–Neelsen (Z–N) staining and sputum collection for Mycobacterium culture on Lowenstein–Jensen media were done. Collection of 2ml heparinized blood for enzyme linked immunospot assay (ELISpot) was done.ResultsThe results of this study showed that all patients were complaining of cough and expectoration. Tuberculin skin test was positive in 18 patients (60%). Most patients (46.6%) had moderately advanced disease as regards the radiological extent. It was found that the median INF-γ ELISpot response to ESAT-6 was significantly decreased after 2months of antituberculosis therapy. The number of pre-treatment ESAT-6 ELISpot count in patients with positive tuberculin skin test was significantly higher than those with negative tuberculin skin test (P<0.01). As regards bacillary load, a statistical significant difference between patients with AFB+++ and patients with (AFB+, AFB++) as regards pre-treatment ELISpot count was recorded. Higher statistical significant difference in patients with AFB+, AFB++ and AFB+++ pre and post treatment ESAT-6 ELISpot count was found. It was found that the number of pre-treatment ESAT-6 ELISpot count in patients with cavitary lesion was higher than those without cavitary lesion and the difference was highly significant (P=0.01). As regards radiological extent, it was found that the number of pre-treatment ESAT-6 ELISpot count in patients with far advanced disease was higher than patients with minimal or moderately advanced disease. Also, after 2months of therapy the number of ESAT-6 ELISpot count in patients with far advanced disease showed more decline than patients with minimal or moderately advanced disease. It was found that ELISpot assay sensitivity, specificity, positive predictive value and negative predictive value in relation to L.J. media were 93.3%, 100%, 100% and 88.2%, respectively.ConclusionELISpot assay may be used as a useful tool in the diagnosis of pulmonary tuberculosis. The decrease in the M. tuberculosis-specific T cell responses following 2months of successful antituberculosis therapy may have a clinical value as a supplemental tool for the monitoring treatment response of pulmonary tuberculosis patients.

Validity and Interrater Reliability of a Regional Mock Oral Board Examination

There have been decreasing pass rates recently on the American Board of Surgery Certifying Examination (ABSCE). General surgery residents from the University of Pittsburgh Medical Center, the West Penn Allegheny Health System, the Conemaugh Health System, and Mercy Hospital participate in a mock oral board examination, which is similar to the ABSCE. The aims of the study are to compare examinee performance on the mock oral boards with the ABSCE and to evaluate the interrater reliability of examiner pairs. In this retrospective study from 2003 to 2010, outcomes on the mock oral boards and the first attempt of the ABSCE for chief residents were compared for the 4 regional residency programs. Interrater reliability for examiner pairs was evaluated with agreement and kappa statistics. Nonparametric statistics were performed, with α = 0.05. A total of 32 of 38 (84.2%) chief residents passed the mock oral boards. The median score for each of the 3 rooms was 6 (clear pass). A total of 37 of 38 (97.4%) residents passed the ABSCE. The sensitivity of the mock oral boards was 83.8%, with a positive predictive value of 96.9%, and an accuracy of 81.6%. A total of 25 of 47 (53.2%) examiner pairs were from the same residency institution, whereas 22 of 47 (46.8%) were from different institutions. The median agreement was 100% (interquartile range (IQR) [100% - 100%]). The median kappa statistic was 1.00 (IQR [0.38-1.00]). The Mann-Whitney U tests showed no difference in agreement or kappa for examiner pairs from the same or from different institutions (p> 0.05). The mock oral boards have substantial sensitivity and positive predictive value in relation to the ABSCE. There are also very high levels of interrater agreement and interrater reliability. This regional mock oral board examination is valuable for ABSCE preparation.

Interrelationships between Tooth Properties and Biochemical Bone Turnover Markers Investigated on Six-Month-Old Pig Model

The aim of the study was to determine interrelationships between bone tissue metabolism indices and morphological, biomechanical and densitometric properties of hard dental tissues. First primary maxillary incisor from 6-month-old pigs (N=27) was evaluated in terms of weight and length. Mean volumetric tooth mineral density, total tooth volume, enamel total volume, enamel volumetric mineral density, dentine total volume and dentine volumetric mineral density were estimated with the use of quantitative computed tomography and micro computed tomography techniques. Tooth mineral density and tooth mineral content were evaluated with the use of dual-energy X-ray absorptiometry. Microhardness of enamel was measured using Vicker's test. Evaluations of total calcium, ionized calcium, magnesium, phosphorus, alkaline phosphatase, bone alkaline phosphatase, osteocalcin, C-terminal telopeptide of type-I collagen (CTX), insulin-like growth factor-1, growth hormone and parathyroid hormone were performed in plasma and serum samples. Pearson's correlation coefficients were determined between all the investigated variables, and P<0.05 was considered as statistically significant. The obtained results have shown mainly mutual dependences between biochemical indicators of bone metabolism. Evaluation of CTX concentration in serum of pigs has shown the highest predictive value in relation to morphological, densitometric and biomechanical properties of teeth.

The Influence of Inflammatory Markers and CRP Predictive Value in Relation to the Target Hemoglobin Level in Patients on Chronic Hemodialysis

The aim of this study was to determine the influence of inflammatory markers, predictive values of CRP and target hemoglobin (Hb) in patients on chronic hemodialysis. Made is a cross-sectional study of inflammatory agents serum levels-CRP, fibrinogen and ferritin before hemodialysis in 114 patients divided into two groups according to the achieved or unachieved target hemoglobin level in the Cantonal Hospital in Zenica. The 57 patients (test group) did not reached the target hemoglobin in the range from 10-12 g/dl and CRP values were significantly higher compared to the control group (57 patients) who had reached targeted hemoglobin values. Levels of fibrinogen and ferritin were not significantly different between the control and the test group. CRP values are in negative correlation with the Hb concentration, while fibrinogen and ferritin values had a positive correlation. Significant negative correlation was only found in case of CRP, respectively, higher CRP was at lower levels of blood Hb. It was found that the predictive value of CRP is 6.5 mg/L to achieve target Hb level. If the CRP increases by 1 mg/L, possibilities to achieve the target Hb level in dialysis patients is reduced by 7.5%, with a sensitivity of 51% and specificity of 77%. Ferritin was elevated due to iatrogenic iron saturation, because all patients received intravenous iron and was treated with erythropoietin. By identification and analysis of inflammatory agents and duration ofhemodialysis, are explored the primary influence on hematopoiesis, of course, with the primary application of erythropoietin and adjuvant agents. It has been shown that CRP alone has an impact on the target Hb level, depending on the hemodialysis duration. The research results show how what looks as routine findings may be helpful in the timely detection of threatening complications and their treatment, and provide extended and improved quality of life for patients on hemodialysis.

T-Cell Profiling Shows Marked Differences in Gene Expression Between Tumour Infiltrating (TIL) and Peripheral Blood (PB) Antibody-Bead Selected T-Cells From Fresh Lymph Node and PB Samples in Follicular Non-Hodgkin's Lymphoma (FL): Possible implications for Immunomodulatory Therapy

Abstract 683 Introduction:FL is one of the commonest B-cell lymphomas accounting for 25–30% of all newcases of non-Hodgkin’s lymphoma. Median survival ranges from 6–10 years with a constant annual rate of relapse and death. The cellular immune system through T-cells and macrophages/monocytes (MMs) has an important role in the response to therapy and long term remissions. Evidence for this stemmed from increased incidence and the poor response rates and survival in patients with inherited or acquired T-cell defects, and the graft-versus-leukaemia effect of allogeneic stem cell transplants. The number of tumour infiltrating lymphocytes (TILs) and MMs appear to predict clinical response and outcome in FL. A recent National Cancer Institute study looked at the prediction of survival in FL based on the molecular features of TILs with positive findings. However, this study used frozen material which could have changed the signatures, T-cells were not positively selected and would have been mixed with other non B-cells, negatively selected cells were stimulated with CD3 which could have changed the gene expression profile, the study looked only at the predictive value in relation to prognosis and did not look at PB T-cell (PBT)profile. Aims and methods:In the first stage reported here, we looked at positively selected TILs, PBT and MMs gene expression profile signatures in fresh lymph node samples (LNs) of histologically confirmed grades 1–3 FL in 14 patients and compared the profile results with similar cells positively selected from PB samples taken at the same time. The analysis was controlled with 4 histologically proven reactive hyperplasia LNs. Tissue samples were digested with a cocktail of enzymes, ficol separated and then positively selected for CD2, CD19, CD14 in that order using Dynabeads (Dynall) initially then Microbeads (Miltenyl Biotech) subsequently. CD2 was used to avoid T-cell receptor stimulation and change of expression with CD3. Some isolated T-cells were initially expanded in culture for purity assessment only by flow cytometry. T-cells and MMs were liquid nitrogen frozen in trisol whilst B-cells were stored in DMSO. RNA was extracted at the same time and analysed using Affymetrix Microarray Chips. Statistical analysis used 3 parameters to define significant change in expression: fold change of >1.5, p value of > 1×10−3and FDR of >0.5. Samples were analysed as paired and pooled as some cases did not yield adequate paired samples. Results:T-cell paired (10) samples showed 97 over (41) or under (56) expressed genes in TILs compared to PBT whilst pooled samples (14) showed 778 over (380) or under (398) expressed genes. The top over expressed genes (10 fold plus) using both methods of analysis were CXCL13 a B-cell chemotactic gene, IGJ which helps in assembling IgG and IgM, CTLA4 a regulatory molecule, CD200 which delivers an inhibitory signal for the macrophage lineage and several heat shock protein (HSP) genes. The top under-expressed genes (10 fold plus) include genes that regulate T-cell adhesion, migration and direct and indirect cytotoxicity such as a number of FC receptor genes needed for antibody dependant cell cytotoxicity, killer cell lectin-like receptor genes, fractalkine genes involved in the adhesion and migration of leukocytes, and granzyme, granulosin, lysosyme and other genes involved in T-cell cytotoxocity. MMs: Only pooled samples were analysed as the extracted cell numbers were too small to have paired analysis. Many more (3239) genes were over (1494) or under (1745) expressed in LN MMs compared to PB MMs. The top over expressed genes include genes that support B cell growth such as IGJ, BLNK and C4orf7, the B cell chemotactic gene CXCL13, signal transduction inhibitors and HSPs. The top underexpressed genes include those that regulate cell adhesion and survival, cell proliferation and migration and extracellular matrix assembly. Others include FC receptor, IL-1 and compliment genes necessary for cell cytotoxicity, and thrombomodulin genes. Conclusion:We believe this is novel data suggesting that TILs and tissue MMs appear to support B-cell growth in FL whilst inheriting several defects in direct and indirect cell cytotoxicity. Downregulating the significantly overexpressed and upregulating the under expressed genes through targeted therapy may provide the basis of non-chemotherapy immunomodulatory treatment of B-cell lymphomas. Disclosures:Rassam:BMS: Honoraria; Johnson and Johnson: Unrestricted research grant Other; ROCHE: Honoraria. Mufti:Celgene: Consultancy, Research Funding.

The Prognostic and Predictive Value of Combined HE4 and CA-125 in Ovarian Cancer Patients

A risk-of-ovarian-malignancy algorithm (ROMA) based on human epididymis protein 4 (HE4) and CA-125 has been reported to categorize women with a pelvic mass into high or low risk of ovarian malignancy. Originally, the ROMA score was developed for diagnostic purposes and the clinical application of HE4 for other purposes such as a predictor of survival or platinum resistance has not been extensively investigated. The objective of the present study was to evaluate the prognostic importance of prechemotherapy combined levels of HE4 and CA-125 and prediction of platinum resistance. Furthermore, we wanted to investigate the dynamics of the markers during treatment. Serum from 137 patients with newly diagnosed serous ovarian cancer was analyzed for CA-125 and HE4 using ELISAs in a training data set. Patients with high levels (upper third percentiles) of both HE4 and CA-125 were classified as high-risk patients. Data were validated in an independent data set of an additional 94 patients. HE4 and CA-125 were also analyzed at all cycles of subsequent chemotherapy. The combined score of HE4 and CA-125 was highly predictive of both progression-free and overall survival in univariate as well as multivariate survival analysis. Values in the upper third percentiles (66th) were significantly associated with decreased progression-free and overall survival in both the training and in the validation set (P < 0.05 in all analyses).The positive predictive value in relation to platinum resistance was higher for the combination of markers than for the markers individually. The positive predictive values were 64.3% and 60.7% for combined CA-125/HE4 in the training and validation sets, respectively. The combination of HE4 and CA-125 levels at baseline just before initiation of chemotherapy was significantly associated with decreased progression-free and overall survival and to some extent with platinum resistance.

A Meta-analysis of 64-section Coronary CT Angiography Findings for Predicting 30-day Major Adverse Cardiac Events in Patients Presenting with Symptoms Suggestive of Acute Coronary Syndrome

To determine the accuracy of 64-section coronary computed tomography angiography (CCTA) in predicting 30 day major adverse cardiac events (MACE) for patients presenting with symptoms concerning for acute coronary syndrome (ACS). Electronic databases between January 1, 2005, and May, 1, 2011, and reference lists from relevant published research articles were searched. We included studies on adult patients who presented with active symptoms suggestive of ACS, had immediate 64-section CCTA performed and were assessed for MACE at a minimum of 30 days past their initial presentation. Studies had to report or provide sufficient detail to determine sensitivity, specificity, positive predictive value, and negative predictive value in relation to MACE using a 50% diameter stenosis as cutoff criterion for coronary artery disease. Nine studies were included for a total of 1559 patients studied (42.3% women, mean age 51.9 ± 10.6). Patients ranged from low to intermediate risk for ACS. All had initial inconclusive electrocardiograms and negative cardiac biomarker results. A total of 14.8% of patients had a positive CCTA result. The pooled sensitivity was 93.3% (95% CI 88.3%-96.6%), specificity was 89.9% (95% CI 88.3%-91.3%), positive predictive value was 48.1% (95% CI 42.5%-53.8%), and negative predictive value was 99.3% (95% CI 98.7%-99.6%). Sixty-four section CCTA had a 99.3% negative predictive value in excluding MACE for 30 days after initial symptom presentation in 85.2% of our study population. Although the value of 64-section CCTA is best for identifying patients who can safely be discharged home, it is less useful for patients who have positive results.

P03-452 - Differences in the prevalence of insomnia and their predictive value in patients with deliberate drug self-poisoning

IntroductionEvidence suggests a relationship between sleep disturbances and suicidal ideation. The temporal appearance of insomnia has been proposed as a warning sign of imminent suicidal acts. However, there is little information on the temporal relation of insomnia with acts of deliberate self-poisoning (DSP) in particular.ObjectivesThis study aimed to identify the insomnia prevalence in DSP patients and test its predictive value in relation to current psychiatric diagnosis and history of previous DSP acts.MethodsSeventy consecutive patients with DSP admitted from February to September 2010 into three general hospitals had a psychiatric consultation and their sleeping pattern during the week before the DSP act was assessed using the Athens Insomnia Scale.ResultsPatients, with a mean age of 34 ± 2 years, predominantly women (70%), were diagnosed with personality disorders (68%), depression (22%) and psychosis (10%). The overall insomnia prevalence was 69%. A chi-square analysis showed that patients with an Axis I diagnosis were significantly more likely to present insomnia than patients with an Axis II diagnosis. Interestingly, when the number of previous DSP acts was included into the analysis, patients with an Axis I diagnosis with and without previous DSP acts had an equal prevalence of insomnia. On the contrary, in patients with an Axis II diagnosis and previous DSP acts, insomnia was three times more prevalent than in those with no previous DSP acts.ConclusionsThese results suggest that insomnia may be a valid proximal warning sign, particularly in patients with personality disorders and previous DSP acts.

Value of IgA human recombinant tissue transglutaminase antibody test in diagnosis of symptomatic celiac disease in children

Objective: To identify the value of serological examination in diagnosis of celiac disease in children. Patients and methods: A prospective case series study was conducted at private clinics in Mosul city during the period from 30th of October 2007 to 30 th of October 2009. A total of 40 patients (29 males, 11 females) aged more than 6 months on gluten containing diet presented with symptoms suggestive of celiac disease were screened by serological testing using second generation ELISAs IgA human recombinant tissue transglutaminase antibody. Multiple duodenal biopsies were performed for every patient enrolled in this study regardless of the results of serology. Statistical methods were used to indicate sensitivity, specificity, negative and positive predictive values of serological test in comparison to biopsy results. Results: A total of 16 (40%) out of 40 symptomatic patients with mean age of 51 months, demonstrated both positive IgA anti-tissue transglutaminase antibody test and biopsy results for celiac disease, the remaining 24 patients (60%) displayed negative results for both serology and biopsy. IgA anti-tissue transglutaminase antibody test had (100%) specificity, sensitivity, positive predictive value, and negative predictive value in relation to biopsy results. Conclusion: Our results provide additional support to the concept that IgA anti-tissue transglutaminase antibodies can be used as a diagnostic serologic marker for celiac disease.

Predictive and prognostic markers for the outcome of chemotherapy in advanced colorectal cancer, a retrospective analysis of the phase III randomised CAIRO study

We have tested several biomarkers [dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT), thymidine phosphorylase (TP), thymidylate synthase (TS) and excision cross-complementing gene (ERCC1)] for their prognostic and predictive value in relation to the outcome of chemotherapy in tumour tissues of 556 advanced colorectal cancer (ACC) patients who were randomised between sequential treatment and combination treatment in the CApecitabine, IRinotecan, Oxaliplatin (CAIRO) study. DPD expression showed a statistically significant predictive value for combination treatment with capecitabine plus irinotecan with low versus high values resulting in an improved median progression-free survival (PFS) and median overall survival (OS) of 8.9 (95% confidence interval (CI) 8.3–9.9) versus 7.2 months (95% CI 6.5–8.1, p = 0.006), and 21.5 months (95% CI 17.9–26.5) versus 16.9 months (95% CI 13.0–19.1, p = 0.04), respectively. In the overall patient population a high OPRT expression in stromal cells was a favourable prognostic parameter for OS, with 21.5 months (95% CI 17.9–27.3) versus 17.2 months (95% CI 15.1–18.6, p = 0.036), respectively. A similar effect was observed for PFS. In a multivariate analysis that included known prognostic factors these results remained significant and also showed that a high OPRT expression in tumour cells was an unfavourable prognostic parameter for PFS and OS. In conclusion, in this largest study on capecitabine with or without irinotecan to date we found a predictive value of DPD expression. Our results on the prognostic value of OPRT expression warrant further studies on the role of stromal cells in the outcome of treatments. The divergent results of ours and previous studies underscore the complexity of these biomarkers and currently prevent the routine use of these markers in daily clinical practice.

The complex enterprise of modelling prenatal exposure to cigarettes: what is 'enough'?

While there is a burgeoning body of research linking smoking during pregnancy to problem behaviour in offspring, a major criticism of this work has been the crude measurement of exposure in these studies (e.g. retrospective, self-reported only) that could lead to biased estimates. To address this issue, we used a pregnancy cohort with repeated prospective measures of exposure as well as biological assays to generate estimates of exposure patterns using a range of modelling techniques. In this paper we report on the analytical approaches we have developed, including patterns of exposure over time and best-estimate approaches that combine self-report and cotinine measures, and compare their predictive value in relation to different dimensions of fetal growth as a first step towards examining the utility of greater precision of exposure measurement. Surprisingly, in this sample the more complex assessments of exposure, including biological measures, generally did not perform better than simple indicators of exposure based on repeated self-report measures, with one exception: a combined self-report cotinine 'best estimate' of third trimester exposure was uniquely associated with lower brain : body ratio. Further study is needed using more sophisticated cotinine assays and testing prediction of a range of outcomes to ascertain whether these findings represent true differences or are specific to the sample, methods and outcomes used. Such research will inform the development of guidelines for adequate exposure characterisation in developmental studies.

Potential Role for Plasma Placental Growth Factor in Predicting Coronary Heart Disease Risk in Women

The purpose of this study was to examine placental growth factor's (PlGF) predictive value in relation to coronary heart disease (CHD) risk in healthy women. Among 32 826 women from the Nurses' Health Study who provided blood samples at baseline, 453 CHD events were documented during 14 years of follow-up. Controls were matched to cases (2:1) for age, smoking, fasting status, and date of blood sampling. PlGF was inversely correlated with HDL-cholesterol (HDL-C), and positively correlated with several coronary risk factors. In multivariate models, women in the highest versus lowest quintile of PlGF had a greater risk of CHD (RR: 1.58; 95% CI: 1.03 to 2.41). Additional adjustment for many coronary risk factors did not substantively alter this relationship, but HDL-C attenuated the association (RR: 1.25; 95% CI: 0.81 to 1.94). In exploratory time to event analysis, higher PlGF levels, measured >10 years before CHD event, but not <10 years preclinical event, were associated with increased risk of CHD, even after adjustment for comorbid conditions and HDL-C levels (RR: 2.79; 95% CI: 1.19 to 6.56). Elevated prediagnostic PlGF levels were modestly associated with subsequent risk of CHD events and results were attenuated after controlling for HDL-C. PlGF may be most strongly associated with long-term prediction of CHD, consistent with a potential role in early plaque formation and growth.

Meiotic spindle and zona pellucida characteristics as predictors of embryonic development using polscope imaging

OBJECTIVE: To evaluate and analyze the characteristics of meiotic spindle (MS) and zona pellucida (ZP) of oocytes using the PolScope, and to assess their influence on embryonic development. DESIGN: A retrospective study. MATERIALS AND METHODS: The study group consisted of 270 metaphase II oocytes obtained from 79 patients. The average age was 38.4±4.8. The study was approved by our clinical board allowing informed consent. Oocyte retrieval was scheduled 36 h after hCG 5,000IU. The oocytes were placed in an incubator for 3h, before spindle imaging, and confirmed by the presence of the first polar body. For spindle imaging, each oocyte was placed in an equilibrated 7μl media droplet overlaid with mineral oil in a glass bottomed culture dish. Oocytes were imaged using a Leica DMI 6000 (Leica microsystems) equipped with Oocyte™ imaging system (CRi,USA) controller and CCD camera. The images were acquired at ×400 magnification and the location, length, mean retardance(R) of the MS, and the mean R of inner layer of ZP and its thickness were analyzed using an Oocyte™ imaging system. In order to optimize the spindle and polar body visualization, oocytes were rotated using the holding pipette. After ICSI, oocytes with and without spindles were washed twice and cultured separated and sequentially in fertilization media droplets for further analysis. RESULTS: A total of 270 oocytes from 79 patients were examined, and visualized spindle was confirmed in 81.1%(219/270) oocytes; group A, but was not found in the remaining 18.9%(51/270) oocytes; group B. Fertilization rate was 74.0% (162/219) in group A versus 68.6% (35/51) in group B. There was no significant difference. Blastulation rate(BR) on day 5 was 50.0% (43/86) in group A versus 36.8%(7/19) in group B. There was no significant difference. The R of the inner layer of the ZPwas measured prior to ICSI. Among 86 oocytes which progressed to blastocysts, BR was 78.9% (15/19) in zona retardance (ZR); >3nm, 40.4% (19/47) in ZR; between 2-3 nm, and 44.4% (8/20) in ZR; <2nm. BR on day 5 was significantly higher in ZR; > 3nm than ZR; between 2-3 nm and ZR <2 nm, respectively (P<0.05). Other relationships among spindle R, spindle length, and inner zona thickness were no significant. CONCLUSIONS: The present study shows that ZR > 3 nm has positive predictive value in relation to progression to blastocysts. However, further prospective studies with large patient populations are needed.

Power doppler ultrasonographic monitoring of response to anti–tumor necrosis factor therapy in patients with rheumatoid arthritis

To evaluate the validity, responsiveness, and predictive value of power Doppler ultrasonography (PDUS) monitoring of response to tumor necrosis factor (TNF) blocking agents in rheumatoid arthritis (RA). Three hundred sixty-seven RA patients were prospectively recruited at 25 Spanish centers; complete clinical, laboratory, and PDUS data were obtained on 278 patients. The patients underwent clinical, laboratory, and PDUS assessment at baseline and after 1, 3, 6, and 12 months of anti-TNF treatment, and radiographic assessment of the hands and feet at baseline and 12 months. The Disease Activity Score in 28 joints (DAS28) was recorded at each visit. PDUS examination included 86 intraarticular and periarticular sites in 28 joints. US synovial fluid (SF), synovial hypertrophy (SH), and PD signal were scored in all synovial sites. US count and index for SF, SH, and PD signal were obtained. Sensitivity to change of the PDUS variables was assessed by estimating the smallest detectable difference (SDD) from the intraobserver variability. A significant parallel improvement in DAS28 and PDUS parameters was found at followup assessment (P < 0.0005 for within-subject between-visit changes). The SDD for PDUS parameters was lower than the mean changes throughout followup. Time-integrated values of US joint count for PD signal and rheumatoid factor (RF) showed predictive value in relation to progression of radiographic erosion (R = 0.64), and time-integrated values of US joint count for PD signal, RF, and erythrocyte sedimentation rate were predictors of progression of the total radiographic score (R = 0.59). These findings indicate that PDUS is a valid method for monitoring response to anti-TNF therapy in RA; results obtained by PDUS are reproducible and sensitive to change. PDUS findings may have predictive value in relation to radiologic outcome.

Influence of Previous Chemotherapy on the Efficacy of Subsequent Docetaxel Therapy in Advanced Non-small Cell Lung Cancer Patients

To identify factors, particularly the previous use of paclitaxel, that might influence the efficacy of subsequent docetaxel therapy. The patient characteristics, responses, and survivals were compared between the two groups that had received a combination of carboplatin and paclitaxel (group P), and a combination of a platinum and an agent other than paclitaxel (group NP). A total of 227 patients (127 in group P, and 100 in group NP) were recruited from a hospital-based registry. Two hundred twenty patients were evaluated for the survival, and 210 patients were evaluated for the response of docetaxel therapy. The response rate to docetaxel therapy (14.2% versus 16.0%, p = 0.702) or the median survival time (10.9 months versus 11.1 month, p = 0.567) did not differ between groups P and NP. The results of multivariate analysis, adjusted for sex, age, and performance status at the start of docetaxel therapy, showed that not the regimen per se, but the response to previous chemotherapy significantly influenced the response rate of docetaxel therapy (odds ratio [OR]: 1.38, 95% confidential interval [CI]: 0.63-3.01; and OR: 2.93, 95% CI: 1.28-6.72, respectively). As for the overall survival, neither the response to nor the previous chemotherapy regimen had any impact (hazard ration [HR]: 0.90, 95% CI 0.66-1.22; HR 0.88, 95% CI 0.65-1.20, respectively). The previous use of paclitaxel had no impact on the response or survival to subsequent docetaxel therapy. In contrast, the response to previous chemotherapy had a predictive value in relation to responses to subsequent docetaxel therapy in patients with advanced non-small cell lung cancer.

Oral Hygiene and Parent-Related Factors during Early Childhood in Relation to Approximal Caries at 15 Years of Age

The aim was to investigate whether oral hygiene habits and parent-related factors, recorded in early childhood, have a predictive value in relation to approximal caries experience (including initial caries lesions) at the age of 15 years (n = 568). Data were selected from examinations, interviews and questionnaires at 1 and 3 years and bitewing radiographs at 15 years. Four levels of cut-off points for the statistical analysis were used: DFa = 0, > 0, ≧4 and ≧8. In the final logistic regression analyses, mother’s self-estimation of her oral health care being less good remained statistically significant and predicted a caries experience of DFa > 0 at 15 years. The following four variables predicted DFa ≧4: (1) female gender, (2) plaque on maxillary incisors at 1 year, (3) mother’s self-estimation of her oral health care being less good and (4) father being less satisfied with his social situation. Two variables predicted DFa ≧8: (1) toothbrushing with fluoride toothpaste just once a day, and (2) father being less satisfied with his social situation. Furthermore, children who failed to attend the examination at 1 year of age had 6.95 ± 5.36 (mean ± SD) DFa at 15 years compared with 3.10 ± 3.85 for children who were examined at 1 year of age (p < 0.01). To conclude, factors explaining good dental health at 15 years of age pertained to both children and parents. Thus, it seems that good oral hygiene habits, established in early childhood, provide a foundation for a low experience of approximal caries in adolescents.

P1-119: Tissue and serum EGFR as prognostic factors in malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is an uncommon but extremely aggressive tumor of the pleura which has been closely linked to asbestos exposure. Over the last decade, a variety of receptor tyrosine kinases have been identified to play a central role in various aspects of tumorigenesis. One of these, EGFR, is overexpressed in the majority of MPMs and appears to play an important role in the pathogenesis of the disease. The aim of the present study was to investigate the potential value of tissue and serum EGFR for the diagnosis of MPM and to assess its predictive value in relation to survival. We prospectively investigated 90 cases of pathologically-proven MPM presenting at NCI Cairo. All cases were confirmed using immunohistochemical markers. Epithelioid cases were positive to calretinine, mesothelioma antigen, keratin 5/6 and negative to epithelial membrane antigen and/or cytokeratin and/or CEA. Sarcomatoid cases were diagnosed by being positive for mesothelioma antigen and negative for vimentin. Out of the 90 MPM cases, 71 and 40 had undergone determination of the EGFR on the tissue and serum respectively. Major clinical characteristics in MPM patients were: a median age 46, range (26-77) years, a M/F ratio 1.7:1, 28.2% of the cases were early stage, 35% had a performance status 2 and 70% gave a history of asbestos exposure. 57.8% of the cases were epithelioid, 23.3% were mixed, and 7.8% were sarcomatoid. Among all treated patients, the overall response rate (RR) was 32.8%. After a median follow up of 29 months, the median overall survival (MOS) was 10 months. Using a cut-off point of 2.5 ng/ml for EGFR in serum (corresponding to the median of marker concentration in MPM), it was found to be significantly associated with advanced stage. Using a normal cut-off value >0.23 ng/ml, a borderline significance with response to treatment was found. EGFR overexpression in tissues and high serum levels were not associated with unfavorable survival outcome. We have previously studied the correlation between EGFR overexpression EGFR in tissue samples in a subset group of this series for a shorter follow-up period (median follow-up), and we reported a highly significant relation between EGFR expression and the OS rate. However, on a prospective, longer follow-up of these patients this significant association was not revealed. 1– A high pretreatment levels of serum EGFR are associated with poor prognosis and unfavorable response to treatment but not with reduced OS. 2– Although increased EGFR expression in tissues is significantly associated with OS rates in a short follow-up period, this significant relation is not revealed on a long term follow-up. The explanation of this needs detailed genetic studies to determine the exact genetic defects (mutations or SNP) that might contribute to poor survival rather than protein overexpression.