Imaging Based Prediction of Pathology in Adult Diffuse Glioma with Applications to Therapy and Prognosis

The overall aggressiveness of a glioma is measured by histologic and molecular analysis of tissue samples. However, the well-known spatial heterogeneity in gliomas limits the ability for clinicians to use that information to make spatially specific treatment decisions. Magnetic resonance imaging (MRI) visualizes and assesses the tumor. But, the exact degree to which MRI correlates with the actual underlying tissue characteristics is not known. In this work, we derive quantitative relationships between imaging and underlying pathology. These relations increase the value of MRI by allowing it to be a better surrogate for underlying pathology and they allow evaluation of the underlying biological heterogeneity via imaging. This provides an approach to answer questions about how tissue heterogeneity can affect prognosis. We estimated the local pathology within tumors using imaging data and stereotactically precise biopsy samples from an ongoing clinical imaging trial. From this data, we trained a random forest model to reliably predict tumor grade, proliferation, cellularity, and vascularity, representing tumor aggressiveness. We then made voxel-wise predictions to map the tumor heterogeneity and identify high-grade malignancy disease. Next, we used the previously trained models on a cohort of 1,850 glioma patients who previously underwent surgical resection. High contrast enhancement, proliferation, vascularity, and cellularity were associated with worse prognosis even after controlling for clinical factors. Patients that had substantial reduction in cellularity between preoperative and postoperative imaging (i.e. due to resection) also showed improved survival. We developed a clinically implementable model for predicting pathology and prognosis after surgery based on imaging. Results from imaging pathology correlations enhance our understanding of disease extent within glioma patients and the relationship between residual estimated pathology and outcome helps refine our knowledge of the interaction of tumor heterogeneity and prognosis

Towards A Direct Detection of the Spin of Dark Matter

We investigate the contribution of higher spin particles in the signal of direct detection experiments searching for dark matter. We consider a bosonic or fermionic higher spin dark matter (HSDM) candidate which interacts with the Standard Model via a dark U(1) mediator. For a particular subclass of interactions, spin-polarized targets may be used for spin determination: The angular dependence of scatterings can distinguish integer (spin-$s$) vs. half-integer (spin-$s + 1/2$), while the recoil energy dependence of the signal determines $s$. We consider also the signal of a supersymmetric higher spin dark sector, which suggests a characteristic signal (''SUSY Rilles'') for directional direct detection.Comment: Matches published version in PL

PocketNet: A Smaller Neural Network for Medical Image Analysis

Medical imaging deep learning models are often large and complex, requiring specialized hardware to train and evaluate these models. To address such issues, we propose the PocketNet paradigm to reduce the size of deep learning models by throttling the growth of the number of channels in convolutional neural networks. We demonstrate that, for a range of segmentation and classification tasks, PocketNet architectures produce results comparable to that of conventional neural networks while reducing the number of parameters by multiple orders of magnitude, using up to 90% less GPU memory, and speeding up training times by up to 40%, thereby allowing such models to be trained and deployed in resource-constrained settings

Effects of Immunization With the Soil-Derived Bacterium Mycobacterium vaccae on Stress Coping Behaviors and Cognitive Performance in a "Two Hit" Stressor Model

Previous studies demonstrate that Mycobacterium vaccae NCTC 11659 (M. vaccae), a soil-derived bacterium with anti-inflammatory and immunoregulatory properties, is a potentially useful countermeasure against negative outcomes to stressors. Here we used male C57BL/6NCrl mice to determine if repeated immunization with M. vaccae is an effective countermeasure in a "two hit" stress exposure model of chronic disruption of rhythms (CDR) followed by acute social defeat (SD). On day -28, mice received implants of biotelemetric recording devices to monitor 24-h rhythms of locomotor activity. Mice were subsequently treated with a heat-killed preparation of M. vaccae (0.1 mg, administered subcutaneously on days -21, -14, -7, and 27) or borate-buffered saline vehicle. Mice were then exposed to 8 consecutive weeks of either stable normal 12:12 h light:dark (LD) conditions or CDR, consisting of 12-h reversals of the LD cycle every 7 days (days 0-56). Finally, mice were exposed to either a 10-min SD or a home cage control condition on day 54. All mice were exposed to object location memory testing 24 h following SD. The gut microbiome and metabolome were assessed in fecal samples collected on days -1, 48, and 62 using 16S rRNA gene sequence and LC-MS/MS spectral data, respectively; the plasma metabolome was additionally measured on day 64. Among mice exposed to normal LD conditions, immunization with M. vaccae induced a shift toward a more proactive behavioral coping response to SD as measured by increases in scouting and avoiding an approaching male CD-1 aggressor, and decreases in submissive upright defensive postures. In the object location memory test, exposure to SD increased cognitive function in CDR mice previously immunized with M. vaccae. Immunization with M. vaccae stabilized the gut microbiome, attenuating CDR-induced reductions in alpha diversity and decreasing within-group measures of beta diversity. Immunization with M. vaccae also increased the relative abundance of 1-heptadecanoyl-sn-glycero-3-phosphocholine, a lysophospholipid, in plasma. Together, these data support the hypothesis that immunization with M. vaccae stabilizes the gut microbiome, induces a shift toward a more proactive response to stress exposure, and promotes stress resilience. &nbsp;</p

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Towards a direct detection of the spin of dark matter

We investigate the contribution of higher spin particles in the signal of direct detection searches for dark matter. We consider a bosonic or fermionic higher spin dark matter (HSDM) candidate which interacts with the Standard Model via a dark U(1) mediator. For a particular subclass of interactions, spin-polarized targets may be used for spin determination: The angular dependence of scatterings can distinguish integer (spin-s) vs. half-integer (spin-s + 1 / 2), while the recoil energy dependence of the signal determines s. We consider also the signal of a supersymmetric higher spin dark sector, which suggests a characteristic signal (“SUSY Rilles”) for directional direct detection