Improving prostate cancer detection in veterans through the development of a clinical decision rule for prostate biopsy

BACKGROUND: We sought to improve prostate cancer (PC) detection through developing a prostate biopsy clinical decision rule (PBCDR), based on an elevated PSA and laboratory biomarkers. This decision rule could be used after initial PC screening, providing the patient and clinician information to consider prior to biopsy. METHODS: This case–control study evaluated men from the Tampa, Florida, James A. Haley (JH) Veteran’s Administration (VA) (N = 1,378), from January 1, 1998, through April 15, 2005. To assess the PBCDR we did all of the following: 1) Identified biomarkers that are related to PC and have the capability of improving the efficiency of PC screening; 2) Developed statistical models to determine which can best predict the probability of PC; 3) Compared each potential model to PSA alone using Receiver Operator Characteristic (ROC) curves, to evaluate for improved overall effectiveness in PC detection and reduction in (negative) biopsies; and 4) Evaluated dose–response relationships between specified lab biomarkers (surrogates for extra-prostatic disease development) and PC progression. RESULTS: The following biomarkers were related to PC: hemoglobin (HGB) (OR = 1.42 95% CI 1.27, 1.59); red blood cell (RBC) count (OR = 2.52 95% CI 1.67, 3.78); PSA (OR = 1.04 95% CI 1.03, 1.05); and, creatinine (OR = 1.55 95% CI 1.12, 2.15). Comparing all PC stages versus non-cancerous conditions, the ROC curve area under the curve (AUC) enlarged (increasing the probability of correctly classifying PC): PSA (alone) 0.59 (95% CI 0.55, 0.61); PBCDR model 0.68 (95% CI 0.65, 0.71), and the positive predictive value (PPV) increased: PSA 44.7%; PBCDR model 61.8%. Comparing PC (stages II, III, IV) vs. other, the ROC AUC increased: PSA (alone) 0.63 (95% CI 0.58, 0.66); PBCDR model 0.72 (95% CI 0.68, 0.75), and the PPV increased: 20.6% (PSA); PBCDR model 55.3%. CONCLUSIONS: These results suggest evaluating certain common biomarkers in conjunction with PSA may improve PC prediction prior to biopsy. Moreover, these biomarkers may be more helpful in detecting clinically relevant PC. Follow-up studies should begin with replicating the study on different U.S. VA patients involving multiple practices

Short-term studies underestimate 30-generation changes in a butterfly metapopulation

Most studies of rare and endangered species are based on work carried out within one generation, or over one to a few generations of the study organism. We report the results of a study that spans 30 generations (years) of the entire natural range of a butterfly race that is endemic to 35 km2 of north Wales, UK. Short-term studies (surveys in single years and dynamics over 4 years) of this system led to the prediction that the regional distribution would be quite stable, and that colonization and extinction dynamics would be relatively unimportant. However, a longer-term study revealed unexpectedly high levels of population turnover (local extinction and colonization), affecting 18 out of the 20 patches that were occupied at any time during the period. Modelling the system (using the 'incidence function model' (IFM) for metapopulations) also showed higher levels of colonization and extinction with increasing duration of the study. The longer-term dynamics observed in this system can be compared, at a metapopulation level, with the increased levels of variation observed with increasing time that have been observed in single populations. Long-term changes may arise from local changes in the environment that make individual patches more or less suitable for the butterfly, or from unusual colonization or extinction events that take metapopulations into alternative states. One implication is that metapopulation and population viability analyses based on studies that cover only a few animal or plant generations may underestimate extinction threats

Uncertainty estimates and L_2 bounds for the Kuramoto-Sivashinsky equation

We consider the Kuramoto-Sivashinsky (KS) equation in one spatial dimension with periodic boundary conditions. We apply a Lyapunov function argument similar to the one first introduced by Nicolaenko, Scheurer, and Temam, and later improved by Collet, Eckmann, Epstein and Stubbe, and Goodman, to prove that ||u||_2 < C L^1.5. This result is slightly weaker than that recently announced by Giacomelli and Otto, but applies in the presence of an additional linear destabilizing term. We further show that for a large class of Lyapunov functions \phi the exponent 1.5 is the best possible from this line of argument. Further, this result together with a result of Molinet gives an improved estimate for L_2 boundedness of the Kuramoto-Sivashinsky equation in thin rectangular domains in two spatial dimensions.Comment: 17 pages, 1 figure; typos corrected, references added; figure modifie

A low-temperature origin for the planetesimals that formed Jupiter

The four giant planets in the Solar System have abundances of 'metals' (elements heavier than helium), relative to hydrogen, that are much higher than observed in the Sun. In order to explain this, all models for the formation of these planets rely on an influx of solid planetesimals(17). It is generally assumed that these planetesimals were similar, if not identical, to the comets from the Oort cloud that we see today. Comets that formed in the region of the giant planets should not have contained much neon, argon and nitrogen, because the temperatures were too high for these volatile gases to be trapped effectively in ice. This means that the abundances of those elements on the giant planets should be approximately solar. Here we show that argon, krypton and xenon in Jupiter's atmosphere are enriched to the same extent as the other heavy elements, which suggests that the planetesimals carrying these elements must have formed at temperatures lower than predicted by present models of giant-planet formation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62913/1/402269a0.pd

A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes

Securin inhibits the protease separase and must be removed before anaphase to ensure timely chromosome segregation. Here, the authors define a mechanism of securin destruction in prometaphase I in mouse oocytes and demonstrate its importance for successful meiotic progression

On the multispacecraft determination of periodic surface wave phase speeds and wavelengths

Observations of surface waves on the magnetopause indicate a wide range of phase velocities and wavelengths. Their multispacecraft analysis allows a more precise determination of wave characteristics than ever before and reveal shortcomings of approximations to the phase speed that take a predetermined fraction of the magnetosheath speed or the average flow velocity in the boundary layer. We show that time lags between two or more spacecraft can give a qualitative upper estimate, and we confirm the unreliability of flow approximations often used by analyzing a few cases. Using two‐point distant magnetic field observations and spectral analysis of the tailward magnetic field component, we propose an alternative method to estimate the wavelength and phase speed at a single spacecraft from a statistical fit to the data at the other site

Cognitive performance among carriers of pathogenic copy number variants: analysis of 152,000 UK Biobank subjects

Background The UK Biobank is a unique resource for biomedical research, with extensive phenotypic and genetic data on half a million adults from the general population. We aimed to examine the effect of neurodevelopmental copy number variants (CNVs) on the cognitive performance of participants. Methods We used Affymetrix Power Tools and PennCNV-Affy software to analyze Affymetrix microarrays of the first 152,728 genotyped individuals. We annotated a list of 93 CNVs and compared their frequencies with control datasets. We analyzed the performance on seven cognitive tests of carriers of 12 CNVs associated with schizophrenia (n = 1087) and of carriers of another 41 neurodevelopmental CNVs (n = 484). Results The frequencies of the 93 CNVs in the Biobank subjects were remarkably similar to those among 26,628 control subjects from other datasets. Carriers of schizophrenia-associated CNVs and of the group of 41 other neurodevelopmental CNVs had impaired performance on the cognitive tests, with nine of 14 comparisons remaining statistically significant after correction for multiple testing. They also had lower educational and occupational attainment (p values between 10−7 and 10−18). The deficits in cognitive performance were modest (Z score reductions between 0.01 and 0.51), compared with individuals with schizophrenia in the Biobank (Z score reductions between 0.35 and 0.90). Conclusions This is the largest study on the cognitive phenotypes of CNVs to date. Adult carriers of neurodevelopmental CNVs from the general population have significant cognitive deficits. The UK Biobank will allow unprecedented opportunities for analysis of further phenotypic consequences of CNVs

Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE).

AIMS/HYPOTHESIS: Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children. METHODS: In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school. RESULTS: Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers. CONCLUSIONS/INTERPRETATION: Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes

Using Markov chain Monte Carlo methods for estimating parameters with gravitational radiation data

We present a Bayesian approach to the problem of determining parameters for coalescing binary systems observed with laser interferometric detectors. By applying a Markov Chain Monte Carlo (MCMC) algorithm, specifically the Gibbs sampler, we demonstrate the potential that MCMC techniques may hold for the computation of posterior distributions of parameters of the binary system that created the gravity radiation signal. We describe the use of the Gibbs sampler method, and present examples whereby signals are detected and analyzed from within noisy data.Comment: 21 pages, 10 figure