Immunologic aspect of ovarian cancer and p53 as tumor antigen

Ovarian cancer represents the fifth leading cause of death from all cancers for women. During the last decades overall survival has improved due to the use of new chemotherapy schedules. Still, the majority of patients die of this disease. Research reveals that ovarian cancer patients exhibit significant immune responses against their tumor. In this review the knowledge obtained thus far on the interaction of ovarian cancer tumor cells and the immune system is discussed. Furthermore the role of p53 as tumor antigen and its potential role as target antigen in ovarian cancer is summarized. Based on the increased knowledge on the role of the immune system in ovarian cancer major improvements are to be expected of immunotherapy based treatment of this disease

MMP-2 and MMP-9 in normal mucosa are independently associated with outcome of colorectal cancer patients.

BackgroundUpregulation of the matrix metalloproteinases MMP-2 and MMP-9 in various cancers has been associated with worse survival of the patients.MethodsWe assessed MMP-2 and MMP-9 levels in normal colorectal mucosa from colorectal cancer patients in relation to the course of the disease.ResultsA high protein expression of MMP-2 as well as MMP-9 in normal mucosa was found to be correlated with worse 5-year survival. The combination of both parameters was an even stronger prognostic factor. These protein levels were found not to be related to the corresponding single nucleotide polymorphisms of MMP-2 (-1306C>T) and MMP-9 (-1562C>T). Multivariate analyses indicated that the MMP-2 and MMP-9 levels in normal mucosa are prognostic for survival, independent of TNM classification.ConclusionMMP-2 and MMP-9 levels in normal mucosa are indicative of the course of disease in colorectal cancer patients

MMP-2 geno-phenotype is prognostic for colorectal cancer survival, whereas MMP-9 is not.

The prognostic significance of single-nucleotide polymorphisms (SNPs) and tumour protein levels of MMP-2 and MMP-9 was evaluated in 215 colorectal cancer patients. Single-nucleotide polymorphism MMP-2(-1306T) and high MMP-2 levels were significantly associated with worse survival. Extreme tumour MMP-9 levels were associated with poor prognosis but SNP MMP-9(-1562C>T) was not. Tumour MMP levels were not determined by their SNP genotypes

Changes in quality of life into adulthood after very preterm birth and/or very low birth weight in the Netherlands

BACKGROUND: It is important to know the impact of Very Preterm (VP) birth or Very Low Birth Weight (VLBW). The purpose of this study is to evaluate changes in Health-Related Quality of Life (HRQoL) of adults born VP or with a VLBW, between age 19 and age 28. METHODS: The 1983 nationwide Dutch Project On Preterm and Small for gestational age infants (POPS) cohort of 1338 VP (gestational age <32 weeks) or VLBW (<1500 g) infants, was contacted to complete online questionnaires at age 28. In total, 33.8% of eligible participants completed the Health Utilities Index (HUI3), the London Handicap Scale (LHS) and the WHOQoL-BREF. Multiple imputation was applied to correct for missing data and non-response. RESULTS: The mean HUI3 and LHS scores did not change significantly from age 19 to age 28. However, after multiple imputation, a significant, though not clinically relevant, increase of 0.02 on the overall HUI3 score was found. The mean HRQoL score measured with the HUI3 increased from 0.83 at age 19 to 0.85 at age 28. The lowest score on the WHOQoL was the psychological domain (74.4). CONCLUSIONS: Overall, no important changes in HRQoL between age 19 and age 28 were found in the POPS cohort. Psychological and emotional problems stand out, from which recommendation for interventions could be derived

Psychometric precision in phenotype definition is a useful step in molecular genetic investigation of psychiatric disorders

Affective disorders are highly heritable, but few genetic risk variants have been consistently replicated in molecular genetic association studies. The common method of defining psychiatric phenotypes in molecular genetic research is either a summation of symptom scores or binary threshold score representing the risk of diagnosis. Psychometric latent variable methods can improve the precision of psychiatric phenotypes, especially when the data structure is not straightforward. Using data from the British 1946 birth cohort, we compared summary scores with psychometric modeling based on the General Health Questionnaire (GHQ-28) scale for affective symptoms in an association analysis of 27 candidate genes (249 single-nucleotide polymorphisms (SNPs)). The psychometric method utilized a bi-factor model that partitioned the phenotype variances into five orthogonal latent variable factors, in accordance with the multidimensional data structure of the GHQ-28 involving somatic, social, anxiety and depression domains. Results showed that, compared with the summation approach, the affective symptoms defined by the bi-factor psychometric model had a higher number of associated SNPs of larger effect sizes. These results suggest that psychometrically defined mental health phenotypes can reflect the dimensions of complex phenotypes better than summation scores, and therefore offer a useful approach in genetic association investigations

Spectroscopic confirmation of a substantial population of luminous red galaxies at redshifts z ≳ 2

We confirm spectroscopically the existence of a population of galaxies at z greater than or similar to 2 with rest-frame optical colors similar to normal nearby galaxies. The galaxies were identified by their red near-infrared colors in deep images obtained with the Infrared Spectrometer and Array Camera on the Very Large Telescope of the field around the foreground cluster MS 1054-03. Redshifts of six galaxies with J(s)-K-s > 2.3 were measured from optical spectra obtained with the W. M. Keck telescope. Five out of six are in the range, demonstrating that the 2.43 = z = 3.52 J(s)-K-s color selection is quite efficient. The rest-frame ultraviolet spectra of confirmed z > 2 galaxies display a range of properties, with two galaxies showing emission lines characteristic of active galactic nuclei, two having Lyalpha in emission, and one showing interstellar absorption lines only. Their full spectral energy distributions are well described by constant star formation models with ages 1.4-2.6 Gyr, except for one galaxy whose colors indicate a dusty starburst. The confirmed z > 2 galaxies are very luminous: their K-s magnitudes are in the range 19.2-19.9, corresponding to rest-frame absolute V magnitudes from -24.8 to -23.2. Assuming that our bright spectroscopic sample is representative for the general population of J(s)-K-s selected objects, we find that the surface density of red z greater than or similar to 2 galaxies is approximate to0.9 arcmin(-2) to K-s = 21. The surface density is comparable to that of Lyman break-selected galaxies with K-s < 21, when corrections are made for the different redshift distributions of the two samples. Although there will be some overlap between the two populations, most "optical-break" galaxies are too faint in the rest-frame ultraviolet to be selected as Lyman break galaxies. The most straightforward interpretation is that star formation in typical optical-break galaxies started earlier than in typical Lyman break galaxies. Optical-break galaxies may be the oldest and most massive galaxies yet identified at, and they z 1 2 could evolve into early-type galaxies and bulges

Usefulness of coronary calcium scoring to myocardial perfusion SPECT in the diagnosis of coronary artery disease in a predominantly high risk population

Coronary calcium scoring (CCS) adds to the diagnostic performance of myocardial perfusion single-photon emission computed tomography (SPECT) to assess the presence of significant coronary artery disease (CAD). Patients with a high pre-test likelihood are expected to have a high CCS which potentially could enhance the diagnostic performance of myocardial perfusion SPECT in this specific patient group. We evaluated the added value of CCS to SPECT in the diagnosis of significant CAD in patients with an intermediate to high pre-test likelihood. In total, 129 patients (mean age 62.7 +/- A 9.7 years, 65 % male) with stable anginal complaints and intermediate to high pre-test likelihood of CAD (median 87 %, range 22-95) were prospectively included in this study. All patients received SPECT and CCS imaging preceding invasive coronary angiography (CA). Fractional flow reserve (FFR) measurements were acquired from patients with angiographically estimated 50-95 % obstructive CAD. For SPECT a SSS &gt; 3 was defined significant CAD. For CCS the optimal cut-off value for significant CAD was determined by ROC curve analysis. The reference standard for significant CAD was a FFR of &lt; 0.80 acquired by CA. Significant CAD was demonstrated in 64 patients (49.6 %). Optimal CCS cut-off value for significant CAD was &gt; 182.5. ROC curve analysis for prediction of the presence of significant CAD for SPECT, CCS and the combination of CCS and SPECT resulted in an area under the curve (AUC) of 0.88 (95 % CI 81-94), 0.75 (95 % CI 66-83 %) and 0.92 (95 % CI 87-97 %) respectively. The difference of the AUC between SPECT and the combination of CCS and SPECT was 0.05 (P = 0.12). The addition of CCS did not significantly improve the diagnostic performance of SPECT in the evaluation of patients with a predominantly high pre-test likelihood of CAD

Rijkswaterstaat:Guardian of the Dutch Delta

Founded in 1798, Rijkswaterstaat, the Dutch government’s agency for infrastructural works, brought flood security, navigable waterways and highways to the Netherlands. It is an iconic institution within Dutch society, best known for its ‘battle against the water’. The Zuiderzee Works (1920–1968) and the Delta Works (1954–1997) brought worldwide acclaim. This chapter tells the story of a humble semi-military organization that developed into a formidable institution of civil engineers with a strong technocratic mission mystique. It also recounts the institutional crisis the agency experienced in the 1970s–1990s when it was too slow to adapt to major sociocultural and political changes. To ride the waves of change, it eventually developed several proactive adaptation strategies and reinvented its mission mystique in managerial terms. Adaptation to climate change now presents another key challenge, for which Rijkswaterstaat will have to develop a new ‘social license to operate’

Cardiovascular dynamics in ischemic cardiomyopathy during exercise

Cardiac Dysfunction and Arrhythmia