A prospective genome-wide study of prostate cancer metastases reveals association of wnt pathway activation and increased cell cycle proliferation with primary resistance to abiraterone acetate-prednisone.

Background: Genomic aberrations have been identified in metastatic castration-resistant prostate cancer (mCRPC), but molecular predictors of resistance to abiraterone acetate/prednisone (AA/P) treatment are not known. Patients and methods: In a prospective clinical trial, mCRPC patients underwent whole-exome sequencing (n = 82) and RNA sequencing (n = 75) of metastatic biopsies before initiating AA/P with the objective of identifying genomic alterations associated with resistance to AA/P. Primary resistance was determined at 12 weeks of treatment using criteria for progression that included serum prostate-specific antigen measurement, bone and computerized tomography imaging and symptom assessments. Acquired resistance was determined using the end point of time to treatment change (TTTC), defined as time from enrollment until change in treatment from progressive disease. Associations of genomic and transcriptomic alterations with primary resistance were determined using logistic regression, Fisher's exact test, single and multivariate analyses. Cox regression models were utilized for determining association of genomic and transcriptomic alterations with TTTC. Results: At 12 weeks, 32 patients in the cohort had progressed (nonresponders). Median study follow-up was 32.1 months by which time 58 patients had switched treatments due to progression. Median TTTC was 10.1 months (interquartile range: 4.4-24.1). Genes in the Wnt/ß-catenin pathway were more frequently mutated and negative regulators of Wnt/ß-catenin signaling were more frequently deleted or displayed reduced mRNA expression in nonresponders. Additionally, mRNA expression of cell cycle regulatory genes was increased in nonresponders. In multivariate models, increased cell cycle proliferation scores (≥ 50) were associated with shorter TTTC (hazard ratio = 2.11, 95% confidence interval: 1.17-3.80; P = 0.01). Conclusions: Wnt/ß-catenin pathway activation and increased cell cycle progression scores can serve as molecular markers for predicting resistance to AA/P therapy.

Nationally representative equations that include resistance and reactance for the prediction of percent body fat in Americans.

BACKGROUND/OBJECTIVES: Resistance and reactance collected by bioelectrical impedance (BIA) can be used in equations to estimate percent body fat at relatively low cost and subject burden. To our knowledge, no such equations have been developed in a nationally representative sample. SUBJECTS/METHODS: Dual-energy X-ray absorptiometry assessed percent body fat from the 1999 to 2004 National Health and Nutrition Survey was the criterion method for development of sex-specific percent body fat equations using up to 6467 males or 4888 females 8-49 years of age. Candidate variables were studied in multiple mathematical forms and interactions using the Least Absolute Shrinkage and Selection Operator. Models were fit in 2/3's of the data and validated in 1/3 of the data selected at random. Final coefficients, R2 values and root mean square error (RMSE) were estimated in the full data set. RESULTS: Models that included age, ethnicity, height, weight, BMI and BIA assessments (resistance, reactance and height2/resistance) had R2 values of 0.831 in men and 0.864 in women in the full data set. RMSE measurements were between 2 and 3 body fat percentage points, and all equations showed low bias across groups formed by age, race/ethnicity or body mass index category. The addition of triceps skinfold and waist circumference increased the R2 to 0.905 in males and 0.883 in females. Adding other anthropometrics (plus menses in females) had little impact on performance. Reactance and resistance alone (in multiple mathematical forms) performed poorly with R2~0.2. CONCLUSIONS: Equations that included BIA assessments along with demographic and anthropometric variables provided percent body fat assessments that had high generalizability, strong predictive ability and low bias.

Absolute bacterial cell enumeration using flow cytometry.

AIM: To evaluate a flow cytometry protocol that uses reference beads for the enumeration of live and dead bacteria present in a mixture. METHODS AND RESULTS: Mixtures of live and dead Escherichia coli with live:dead concentration ratios varying from 0 to 100% were prepared. These samples were stained using SYTO 9 and propidium iodide and 6-µm reference beads were added. Bacteria present in live samples were enumerated by agar plate counting. Bacteria present in dead samples were enumerated by agar plate counting before treatment with isopropanol. There is a linear relationship between the presented flow cytometry method and agar plate counts for live (R2  = 0·99) and dead E. coli (R2  = 0·93) concentrations of c. 104 to 108 bacteria per ml within mixtures of live and dead bacteria. CONCLUSIONS: Reliable enumeration of live E. coli within a mixture of both live and dead was possible for concentration ratios of above 2·5% live and for the enumeration of dead E. coli the lower limit was c. 20% dead. SIGNIFICANCE AND IMPACT OF THE STUDY: The ability to obtain absolute cell concentrations is only available for selected flow cytometers, this study describes a method for accurate enumeration that is applicable to basic flow cytometers without specialized counting features. By demonstrating the application of the method to count E. coli, we raised points of consideration for using this FCM counting method and aim to lay the foundation for future work that uses similar methods for different bacterial strains.

Prediction of percent body fat measurements in Americans 8 years and older.

BACKGROUND/OBJECTIVES: Although numerous equations to predict percent body fat have been published, few have broad generalizability. The objective of this study was to develop sets of equations that are generalizable to the American population 8 years of age and older. SUBJECTS/METHODS: Dual-emission X-ray absorptiometry (DXA) assessed percent body fat from the 1999-2006 National Health and Nutrition Examination Survey (NHANES) was used as the response variable for development of 14 equations for each gender that included between 2 and 10 anthropometrics. Other candidate variables included demographics and menses. Models were developed using the Least Absolute Shrinkage and Selection Operator (LAASO) and validated in a » withheld sample randomly selected from 11 884 males or 9215 females. RESULTS: In the final models, R(2) ranged from 0.664 to 0.845 in males and from 0.748 to 0.809 in females. R(2) was not notably improved by development of equations within, rather than across, age and ethnic groups. Systematic over or under estimation of percent body fat by age and ethnic groups was within 1 percentage point. Seven of the fourteen gender-specific models had R(2) values above 0.80 in males and 0.795 in females and exhibited low bias by age, race/ethnicity and body mass index (BMI). CONCLUSIONS: To our knowledge, these are the first equations that have been shown to be valid and unbiased in both youth and adults in estimating DXA assessed body fat. The equations developed here are appropriate for use in multiple ethnic groups, are generalizable to the US population and provide a useful method for assessment of percent body fat in settings where methods such as DXA are not feasible.

A novel method for identifying SNP disease association based on maximal information coefficient.

To improve single-nucleotide polymorphism (SNP) association studies, we developed a method referred to as maximal information coefficient (MIC)-based SNP searching (MICSNPs) by employing a novel statistical approach known as the MIC to identify SNP disease associations. MIC values varied with minor allele frequencies of SNPs and the odds ratios for disease. We used a Monte Carlo-based permutation test to eliminate the effects of fluctuating MIC values and included a sliding-window-based binary search whose time-cost was 0.58% that of a sequential search to save time. The experiments examining both simulation and actual data demonstrated that our method is computationally and statistically feasible after reducing the resampling count to 4 times the number of markers and applying a sliding-window-based binary search to the method. We found that our method outperforms existing approaches.

Phonon-assisted electroluminescence from metallic carbon nanotubes and graphene.

We report on light emission from biased metallic single-wall carbon nanotube (SWNT), multiwall carbon nanotube (MWNT) and few-layer graphene (FLG) devices. SWNT devices were assembled from tubes with different diameters in the range 0.7-1.5 nm. They emit light in the visible spectrum with peaks at 1.4 and 1.8 eV. Similar peaks are observed for MWNT and FLG devices. We propose that this light emission is due to phonon-assisted radiative decay from populated pi* band states at the M point to the Fermi level at the K point. Since for most carbon nanotubes as well as for graphene the energy of unoccupied states at the M point is close to 1.6 eV, the observation of two emission peaks at approximately 1.6 +/- approximately 0.2 eV could indicate radiative decay under emission or absorption of optical phonons, respectively.

[Studies on the efficacy of albendazole candy for treatment of intestinal nematode infections].

A single dose of albendazole (candy) 100 mg and 100 mg qd for two days was given respectively to 135 and 321 children who were infected with Enterobius vermicularis. All cases were cured 3wk later according to perianal tape examination. The same drug of 150 mg qd and 200 mg qd for two days was administered respectively to residents with single or multi-infections of Ascaris, hookworm and Trichuris; the egg negative conversion rates of the two dosages were revealed to be 99.4% (466/469) and 99.8% (487/488) for Ascaris infection, 96.8% (91/94) and 94.3% (99/105) for hookworm infection, and 53.4% (228/427) and 76.3% (370/486) for Trichuris infection. The maximal numbers of worm expelled were 100 on d2-3, 88 on d3-5 and 588 on d2-4 for Enterobius, Ascaris and hookworm, respectively; whereas the discharged Trichuris were scarce, merely 4.3 in average. The results exhibited promising efficacy of the drug on Enterobius, Ascaris and hookworm infections, but not so on trichuriasis.