Characterization and Clinical Relevance of ALDHbright Populations in Prostate Cancer

PURPOSE High aldehyde dehydrogenase (ALDH) has been suggested to selectively mark cells with high tumorigenic potential in established prostate cancer cell lines. However, the existence of cells with high ALDH activity (ALDH(bright)) in primary prostate cancer specimens has not been shown so far. We investigated the presence, phenotype, and clinical significance of ALDH(bright) populations in clinical prostate cancer specimens. EXPERIMENTAL DESIGN We used ALDEFLUOR technology and fluorescence-activated cell-sorting (FACS) staining to identify and characterize ALDH(bright) populations in cells freshly isolated from clinical prostate cancer specimens. Expression of genes encoding ALDH-specific isoforms was evaluated by quantitative real-time PCR in normal prostate, benign prostatic hyperplasia (BPH), and prostate cancer tissues. ALDH1A1-specific expression and prognostic significance were assessed by staining two tissue microarrays that included more than 500 samples of BPH, prostatic intraepithelial neoplasia (PIN), and multistage prostate cancer. RESULTS ALDH(bright) cells were detectable in freshly excised prostate cancer specimens (n = 39) and were mainly included within the EpCAM((+)) and Trop2((+)) cell populations. Although several ALDH isoforms were expressed to high extents in prostate cancer, only ALDH1A1 gene expression significantly correlated with ALDH activity (P < 0.01) and was increased in cancers with high Gleason scores (P = 0.03). Most importantly, ALDH1A1 protein was expressed significantly more frequently and at higher levels in advanced-stage than in low-stage prostate cancer and BPH. Notably, ALDH1A1 positivity was associated with poor survival (P = 0.02) in hormone-naïve patients. CONCLUSIONS Our data indicate that ALDH contributes to the identification of subsets of prostate cancer cells of potentially high clinical relevance.

Diversity versus disparity and the role of ecological opportunity in a continental bird radiation

Aim The Neotropical parrots (Arini) are an unusually diverse group which colonized South America in the Oligocene. The newly invaded Neotropics may have functioned as an underused adaptive zone and provided novel ecological opportunities that facilitated diversification. Alternatively, diversification may have been driven by ecological changes caused by Andean uplift and/or climate change from the Miocene onwards. Our aim was to find out whether Arini diversified in a classical adaptive radiation after their colonization of South America, or whether their diversification occurred later and was influenced by more recent environmental change. Location Neotropics. Methods We generated a time-calibrated phylogeny of more than 80% of all Arini species in order to analyse lineage diversification. This chronogram was also used as the basis for the reconstruction of morphological evolution within Arini using a multivariate ratio analysis of three size measurements. Results We found a concentration of size evolution and partitioning of size niches in the early history of Arini consistent with the process of adaptive radia- tion, but there were no signs of an early burst of speciation or a decrease in speci- ation rates through time. Although we detected no overall temporal shifts in diversification rates, we discovered two young, unexpectedly species-rich clades. Main conclusions Arini show signs of an early adaptive radiation, but we found no evidence of the slowdown in speciation rate generally considered a feature of island or lake radiations. Historical processes and environmental change from the Miocene onwards may have kept diversification rates roughly constant ever since the colonization of the Neotropics. Thus, Arini may not yet have reached equilibrium diversity. The lack of diversity-dependent speciation might be a general feature of adaptive radiations on a continental scale, and diversification processes on continents might therefore not be as ecologically limited as in isolated lakes or on oceanic islands.

Heterogeneity and time

Although heterogeneity and time are central aspects of economic activity, it was predominantly the Austrian School of economics that emphasized these two aspects. In this paper we argue that the explicit consideration of heterogeneity and time is of increasing importance due to the increasing environmental and resource problems faced by humankind today. It is shown that neo-Austrian capital theory, which revived Austrian ideas employing a formal approach in the 1970s, is not only well suited to address issues of structural change and of accompanying unemployment induced by technical progress but also can be employed for an encompassing ecological-economic analysis demanded by ecological economics. However, complexity, uncertainty, and real ignorance limit the applicability of formal economic analysis. Therefore, we conclude that economic analysis has to be supplemented by considerations of political philosophy. Copyright 2006 American Journal of Economics and Sociology, Inc..

Transcatheter Aortic Valve Replacement in Bicuspid Aortic Valve Disease.

BACKGROUND Limited information exists describing the results of transcatheter aortic valve (TAV) replacement in patients with bicuspid aortic valve (BAV) disease (TAV-in-BAV). OBJECTIVES This study sought to evaluate clinical outcomes of a large cohort of patients undergoing TAV-in-BAV. METHODS We retrospectively collected baseline characteristics, procedural data, and clinical follow-up findings from 12 centers in Europe and Canada that had performed TAV-in-BAV. RESULTS A total of 139 patients underwent TAV-in-BAV with the balloon-expandable transcatheter heart valve (THV) (n = 48) or self-expandable THV (n = 91) systems. Patient mean age and Society of Thoracic Surgeons predicted risk of mortality scores were 78.0 ± 8.9 years and 4.9 ± 3.4%, respectively. BAV stenosis occurred in 65.5%, regurgitation in 0.7%, and mixed disease in 33.8% of patients. Incidence of type 0 BAV was 26.7%; type 1 BAV was 68.3%; and type 2 BAV was 5.0%. Multislice computed tomography (MSCT)-based TAV sizing was used in 63.5% of patients (77.1% balloon-expandable THV vs. 56.0% self-expandable THV, p = 0.02). Procedural mortality was 3.6%, with TAV embolization in 2.2% and conversion to surgery in 2.2%. The mean aortic gradient decreased from 48.7 ± 16.5 mm Hg to 11.4 ± 9.9 mm Hg (p < 0.0001). Post-implantation aortic regurgitation (AR) grade ≥2 occurred in 28.4% (19.6% balloon-expandable THV vs. 32.2% self-expandable THV, p = 0.11) but was prevalent in only 17.4% when MSCT-based TAV sizing was performed (16.7% balloon-expandable THV vs. 17.6% self-expandable THV, p = 0.99). MSCT sizing was associated with reduced AR on multivariate analysis (odds ratio [OR]: 0.19, 95% confidence intervals [CI]: 0.08 to 0.45; p < 0.0001). Thirty-day device safety, success, and efficacy were noted in 79.1%, 89.9%, and 84.9% of patients, respectively. One-year mortality was 17.5%. Major vascular complications were associated with increased 1-year mortality (OR: 5.66, 95% CI: 1.21 to 26.43; p = 0.03). CONCLUSIONS TAV-in-BAV is feasible with encouraging short- and intermediate-term clinical outcomes. Importantly, a high incidence of post-implantation AR is observed, which appears to be mitigated by MSCT-based TAV sizing. Given the suboptimal echocardiographic results, further study is required to evaluate long-term efficacy.

The association between implicit alcohol attitudes and drinking behavior is moderated by baseline activation in the lateral prefrontal cortex

OBJECTIVE Intense alcohol consumption is a risk factor for a number of health problems. Dual-process models assume that self-regulatory behavior such as drinking alcohol is guided by both reflective and impulsive processes. Evidence suggests that (a) impulsive processes such as implicit attitudes are more strongly associated with behavior when executive functioning abilities are low, and (b) higher neural baseline activation in the lateral prefrontal cortex (PFC) is associated with better inhibitory control. The present study integrates these 2 strands of research to investigate how individual differences in neural baseline activation in the lateral PFC moderate the association between implicit alcohol attitudes and drinking behavior. METHOD Baseline cortical activation was measured with resting electroencephalography (EEG) in 89 moderate drinkers. In a subsequent behavioral testing session they completed measures of implicit alcohol attitudes and self-reported drinking behavior. RESULTS Implicit alcohol attitudes were related to self-reported alcohol consumption. Most centrally, implicit alcohol attitudes were more strongly associated with drinking behavior in individuals with low as compared with high baseline activation in the right lateral PFC. CONCLUSIONS These findings are in line with predictions made on the basis of dual-process models. They provide further evidence that individual differences in neural baseline activation in the right lateral PFC may contribute to executive functioning abilities such as inhibitory control. Moreover, individuals with strongly positive implicit alcohol attitudes coupled with a low baseline activation in the right lateral PFC may be at greater risk of developing unhealthy drinking patterns than others.

Anstrengung bei wiederholter Selbstkontrolle: Effekte impliziter Theorien der Willenskraft auf Herzratenvariabilität

Vergangene Forschung konnte zeigen, dass Ego-Depletion nur dann auftritt, wenn Personen glauben, Willenskraft sei eine limitierte Ressource (Job, Dweck & Walton, 2010). Offen ist die Frage, welche Mechanismen den Effekten impliziter Theorien über Willenskraft auf Selbstkontrolle zugrunde liegen und welche Rolle dabei die Anstrengung spielt. Aus bestehender Forschung lassen sich zwei unterschiedliche Annahmen zu Anstrengung im Ego-Depletion Paradigma ableiten: Einerseits könnte es sein, dass Personen mit einer limitierten impliziten Theorie der Willenskraft versuchen, Ressourcen zu sparen und sich somit weniger stark anstrengen als Personen mit einer nicht-limitierten Theorie. Andererseits kann, basierend auf der Effort-Mobilization Theorie, angenommen werden, dass sich Personen mit einer limitierten Theorie mehr anstrengen, um für die Wahrnehmung mangelnder Ressourcen zu kompensieren. In einem Experiment wurde Herzratenvariabilität, als psychophysiologischer Indikator von Anstrengung, gemessen und in Abhängigkeit von impliziten Theorien über Willenskraft und vorangehender Verausgabung (Depletion) untersucht. Die Ergebnisse suggerieren, dass sich Personen mit einer limitierten Theorie der Willenskraft nach Depletion mehr anstrengen, um die gleiche Leistung zu erbringen, als Personen mit einer nicht-limitierten Theorie. Die Befunde sind somit konsistent mit den Annahmen der Effort-Mobilization Theorie.

Does the Use of Mobile Devices (Tablets and Smartphones) Affect Stated Choice Behavior in Web Surveys? An Application to Environmental Valuation

Web surveys are becoming increasingly popular in survey research. Compared with face-to-face, telephone and mail surveys, web surveys may contain a different and new source of measurement error and bias: the type of device that respondents use to answer the survey questions. To the best of our knowledge, this is the first study that tests whether the use of mobile devices affects survey characteristics and stated preferences in a web-based choice experiment. The web survey was carried out in Germany with 3,400 respondents, of which 12 per cent used a mobile device (i.e. tablet or smartphone), and comprised a stated choice experiment on externalities of renewable energy production using wind, solar and biomass. Our main finding is that survey characteristics such as interview length and acquiescence tendency are affected by the device used. In contrast to what might be expected, we find that, compared with respondents using desktop computers and laptops, mobile device users spent more time to answer the survey and are less likely to be prone to acquiescence bias. In the choice experiment, mobile device users tended to be more consistent in their stated choices, and there are differences in willingness to pay between both subsamples.

Differentiation between Staphylococcus aureus and coagulase-negative Staphylococcus species by real-time PCR including detection of methicillin resistants in comparison to conventional microbiology testing.

BACKGROUND Staphylococcus aureus has long been recognized as a major pathogen. Methicillin-resistant strains of S. aureus (MRSA) and methicillin-resistant strains of S. epidermidis (MRSE) are among the most prevalent multiresistant pathogens worldwide, frequently causing nosocomial and community-acquired infections. METHODS In the present pilot study, we tested a polymerase chain reaction (PCR) method to quickly differentiate Staphylococci and identify the mecA gene in a clinical setting. RESULTS Compared to the conventional microbiology testing the real-time PCR assay had a higher detection rate for both S. aureus and coagulase-negative Staphylococci (CoNS; 55 vs. 32 for S. aureus and 63 vs. 24 for CoNS). Hands-on time preparing DNA, carrying out the PCR, and evaluating results was less than 5 h. CONCLUSIONS The assay is largely automated, easy to adapt, and has been shown to be rapid and reliable. Fast detection and differentiation of S. aureus, CoNS, and the mecA gene by means of this real-time PCR protocol may help expedite therapeutic decision-making and enable earlier adequate antibiotic treatment.

8p23 beta-defensin copy number determination by single-locus pseudogene-based paralog ratio tests risk bias due to low-frequency sequence variations.

BACKGROUND The copy number variation (CNV) in beta-defensin genes (DEFB) on human chromosome 8p23 has been proposed to contribute to the phenotypic differences in inflammatory diseases. However, determination of exact DEFB CN is a major challenge in association studies. Quantitative real-time PCR (qPCR), paralog ratio tests (PRT) and multiplex ligation-dependent probe amplification (MLPA) have been extensively used to determine DEFB CN in different laboratories, but inter-method inconsistencies were observed frequently. In this study we asked which one is superior among the three methods for DEFB CN determination. RESULTS We developed a clustering approach for MLPA and PRT to statistically correlate data from a single experiment. Then we compared qPCR, a newly designed PRT and MLPA for DEFB CN determination in 285 DNA samples. We found MLPA had the best convergence and clustering results of the raw data and the highest call rate. In addition, the concordance rates between MLPA or PRT and qPCR (32.12% and 37.99%, respectively) were unacceptably low with underestimated CN by qPCR. Concordance rate between MLPA and PRT (90.52%) was high but PRT systematically underestimated CN by one in a subset of samples. In these samples a sequence variant which caused complete PCR dropout of the respective DEFB cluster copies was found in one primer binding site of one of the targeted paralogous pseudogenes. CONCLUSION MLPA is superior to PRT and even more to qPCR for DEFB CN determination. Although the applied PRT provides in most cases reliable results, such a test is particularly sensitive to low-frequency sequence variations preferably accumulating in loci like pseudogenes which are most likely not under selective pressure. In the light of the superior performance of multiplex assays, the drawbacks of such single PRTs could be overcome by combining more test markers.