Men with advanced prostate cancer can now take highly targeted hormone therapies at home.

Brenna Cholerton
Nov 1, 2016; 29:210-219
From Research to Practice

Numerous recent works highlight the limited utility of established tumor cell lines in recapitulating the heterogeneity of tumors in patients. More realistic preclinical cancer models are thought to be provided by transplantable, patient-derived tumor xenografts (PDX). Inter- and intra-tumor heterogeneity of PDX, however, present several challenges in developing optimal quantitative pipelines to assess response to therapy. The objective of this work was to develop and optimize image metrics of FDG-PET to assess response to combination docetaxel/carboplatin therapy in a co-clinical trial involving triple negative breast cancer (TNBC) PDX. We characterize the reproducibility of SUV metrics to assess response to therapy and optimize a preclinical PERCIST (µPERCIST) paradigm to complement clinical standards. Considerations in this effort included variability in tumor growth rate and tumor size; solid tumor vs. tumor heterogeneity and necrotic phenotype; and optimal selection of tumor slice versus whole tumor. A test-retest protocol was implemented to optimize the reproducibility of FDG-PET SUV thresholds, SUVpeak metrics, and µPERCIST parameters. In assessing response to therapy, FDG-PET imaging was performed at baseline and +4 days following therapy. The reproducibility, accuracy, variability, and performance of imaging metrics to assess response to therapy were determined. We defined an index—"Quantitative Response Assessment Score (QRAS)"—to integrate parameters of prediction and precision, and thus aid in selecting optimal image metrics of response to therapy. Our data suggests that a threshold value of 25% (SUV25) of SUVmax was highly reproducible (<9% variability). Concordance and reproducibility of µPERCIST were maximized at α=0.7 and β=2.8 and exhibited high correlation to SUV25 measures of tumor uptake. QRAS scores favor SUV25 followed by SUVP14 as optimal metrics of response to therapy. Additional studies are warranted to fully characterize the utility of SUV25 and µPERCIST SUVP14 as image metrics of response to therapy across a wide range of therapeutic regiments and PDX models.

Amir Bashir, Carlos M. Carvalho, P. Richard Hahn, M. Beatrix Jones.

Source: Bayesian Analysis, Volume 14, Number 4, 1075--1090.

Abstract:
A variety of computationally efficient Bayesian models for the covariance matrix of a multivariate Gaussian distribution are available. However, all produce a relatively dense estimate of the precision matrix, and are therefore unsatisfactory when one wishes to use the precision matrix to consider the conditional independence structure of the data. This paper considers the posterior predictive distribution of model fit for these covariance models. We then undertake post-processing of the Bayes point estimate for the precision matrix to produce a sparse model whose expected fit lies within the upper 95% of the posterior predictive distribution of fit. The impact of the method for selecting the zero elements of the precision matrix is evaluated. Good results were obtained using models that encouraged a sparse posterior (G-Wishart, Bayesian adaptive graphical lasso) and selection using credible intervals. We also find that this approach is easily extended to the problem of finding a sparse set of elements that differ across a set of precision matrices, a natural summary when a common set of variables is observed under multiple conditions. We illustrate our findings with moderate dimensional data examples from finance and metabolomics.

Awareness for surprising sensory events is shaped by prior belief inferred from past experience. Here, we combined hierarchical Bayesian modeling with fMRI on an associative learning task in 28 male human participants to characterize the effect of the prior belief of tactile events on connections mediating the outcome of perceptual decisions. Activity in anterior insular cortex (AIC), premotor cortex (PMd), and inferior parietal lobule (IPL) were modulated by prior belief on unexpected targets compared with expected targets. On expected targets, prior belief decreased the connection strength from AIC to IPL, whereas it increased the connection strength from AIC to PMd when targets were unexpected. Individual differences in the modulatory strength of prior belief on insular projections correlated with the precision that increases the influence of prediction errors on belief updating. These results suggest complementary effects of prior belief on insular-frontoparietal projections mediating the precision of prediction during probabilistic tactile learning.

SIGNIFICANCE STATEMENT In a probabilistic environment, the prior belief of sensory events can be inferred from past experiences. How this prior belief modulates effective brain connectivity for updating expectations for future decision-making remains unexplored. Combining hierarchical Bayesian modeling with fMRI, we show that during tactile associative learning, prior expectations modulate connections originating in the anterior insula cortex and targeting salience-related and attention-related frontoparietal areas (i.e., parietal and premotor cortex). These connections seem to be involved in updating evidence based on the precision of ascending inputs to guide future decision-making.

Dell's Precision 7920 Tower workstation is a dual-CPU monster for tasks that can leverage its server-grade hardware and require maximum reliability. Just be prepared for sticker shock if you go all-in like on our test model.

When it comes to 15.6-inch laptops, mobile workstations make gaming rigs look like wimps—and the new king of the hill is Dell's costly but colossal Precision 7540, tested in a maxed-out Xeon/Quadro RTX configuration.

BMW has been spotted testing what appears to be a new performance flagship for the M5 range. Word on the street is that the car, which will likely be dubbed an M5 CS, is powered by a newly developed V-8. Porsche looks to be readying a Cayenne GTS Coupe to help bridge the performance gap between the S and Turbo. The new variant should debut next...

Chinese genome sequencing company, BGI Genomics (BGI), and Australian health-data expert, Pryzm Health (Pryzm) have announced a collaboration designed to bring genome-related precision health services to Australia.

Microchip Announces the 53100A Phase Noise Analyzer for Precision Oscillator Characterization

Identifying gene variants causing monogenic diabetes (MD) increases understanding of disease etiology and allows for implementation of precision therapy to improve metabolic control and quality of life. Here, we aimed to assess the prevalence of MD in youth with diabetes in Lithuania, uncover potential diabetes-related gene variants, and prospectively introduce precision treatment. First, we assessed all pediatric and most young-adult patients with diabetes in Lithuania (n = 1,209) for diabetes-related autoimmune antibodies. We then screened all antibody-negative patients (n = 153) using targeted high-throughput sequencing of >300 potential candidate genes. In this group, 40.7% had MD, with the highest percentage (100%) in infants (diagnosis at ages 0–12 months), followed by those diagnosed at ages >1–18 years (40.3%) and >18–25 years (22.2%). The overall prevalence of MD in youth with diabetes in Lithuania was 3.5% (1.9% for GCK diabetes, 0.7% for HNF1A, 0.2% for HNF4A and ABCC8, 0.3% for KCNJ11, and 0.1% for INS). Furthermore, we identified likely pathogenic variants in 11 additional genes. Microvascular complications were present in 26% of those with MD. Prospective treatment change was successful in >50% of eligible candidates, with C-peptide >252 pmol/L emerging as the best prognostic factor.

Neuroscience has had a tough run of news lately. With Amgen deprioritizing neuro this year, Pfizer doing the same last year, and others like BMS, GSK, and AZ cutting back on CNS a few years earlier, it would seem dark

The post The Promise Of Precision Neuroscience And Launch Of Arkuda Therapeutics appeared first on LifeSciVC.

Last week, the New York Times had a nice piece “A Faster Way to Try Many Drugs on Many Cancers” on basket clinical trials, which matches patients to a therapy based on the genetics of their tumor as opposed to the site of their primary tumor. This type of trial feeds into the current excitement about precision