An imaging biomarker of tumor-infiltrating lymphocytes to risk-stratify patients with HPV-associated oropharyngeal cancer

BACKGROUND: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has excellent control rates compared to nonvirally associated OPSCC. Multiple trials are actively testing whether de-escalation of treatment intensity for these patients can maintain oncologic equipoise while reducing treatment-related toxicity. We have developed OP-TIL, a biomarker that characterizes the spatial interplay between tumor-infiltrating lymphocytes (TILs) and surrounding cells in histology images. Herein, we sought to test whether OP-TIL can segregate stage I HPV-associated OPSCC patients into low-risk and high-risk groups and aid in patient selection for de-escalation clinical trials. METHODS: Association between OP-TIL and patient outcome was explored on whole slide hematoxylin and eosin images from 439 stage I HPV-associated OPSCC patients across 6 institutional cohorts. One institutional cohort (n = 94) was used to identify the most prognostic features and train a Cox regression model to predict risk of recurrence and death. Survival analysis was used to validate the algorithm as a biomarker of recurrence or death in the remaining 5 cohorts (n = 345). All statistical tests were 2-sided. RESULTS: OP-TIL separated stage I HPV-associated OPSCC patients with 30 or less pack-year smoking history into low-risk (2-year disease-free survival [DFS] = 94.2%; 5-year DFS = 88.4%) and high-risk (2-year DFS = 82.5%; 5-year DFS = 74.2%) groups (hazard ratio = 2.56, 95% confidence interval = 1.52 to 4.32; P \u3c .001), even after adjusting for age, smoking status, T and N classification, and treatment modality on multivariate analysis for DFS (hazard ratio = 2.27, 95% confidence interval = 1.32 to 3.94; P = .003). CONCLUSIONS: OP-TIL can identify stage I HPV-associated OPSCC patients likely to be poor candidates for treatment de-escalation. Following validation on previously completed multi-institutional clinical trials, OP-TIL has the potential to be a biomarker, beyond clinical stage and HPV status, that can be used clinically to optimize patient selection for de-escalation

Anisotropic Magneto-Thermopower: the Contribution of Interband Relaxation

Spin injection in metallic normal/ferromagnetic junctions is investigated taking into account the anisotropic magnetoresistance (AMR) occurring in the ferromagnetic layer. It is shown, on the basis of a generalized two channel model, that there is an interface resistance contribution due to anisotropic scattering, beyond spin accumulation and giant magnetoresistance (GMR). The corresponding expression of the thermopower is derived and compared with the expression for the thermopower produced by the GMR. First measurements of anisotropic magnetothermopower are presented in electrodeposited Ni nanowires contacted with Ni, Au and Cu. The results of this study show that while the giant magnetoresistance and corresponding thermopower demonstrates the role of spin-flip scattering, the observed anisotropic magnetothermopower indicates interband s-d relaxation mechanisms.Comment: 20 pages, 4 figure

Impact of daily consumption of Moringa (Moringa oleifera) dry leaf powder on iron status of Senegalese lactating women

A randomized study was conducted to test the efficacy of Moringa powder on iron status and weight gain in women. In an open-labelled randomized trial, 82 moderately anaemic, lactating women, aged 26.7� 6.5 years, received a weekly dose of either 100g of Moringa powder(Moringa group) or 120 mg iron sulphate with 0.5 mg folicacid (Control group). Data from 64 women (33 from Moringa group and 31 from Control group) were analyzed. Baseline parameters, socio-economic, anthropometry, haematology, plasma ferritin, and acute phase proteins were comparable in both groups. Low plasma ferritin (< 12 �g/l) indicating iron deficiency was found in 13 and 14 women from the Moringa and Control groups, respectively. After 3 months oftreatment, mean haemoglobin concentrations significantly increased in both groups (p<0.001) but iron stores were unchanged in the Moringa group while they significantly increased in the Control group indicating that consumption of Moringa leaves failed to restore iron stores in anaemic subjects. A slight improvement was observed in the prevalence of anaemia in both groups but anaemia still persisted due to other reasons than iron deficiency anaemia. None of the groups gained weightduring the 3 months. However, the average weight lost was less important in the Moringa group (-0.8 � 2.1 kg) compared to the control group (-1.2� 2.3 kg) but the difference was not significant (p=0.45).The amount of digestible protein in the powder could suggest that the consumption of Moringa was beneficial to the rural women by preventing weight loss during the rainy season. Micronutrient status improvement of vulnerable people in developing countries like Senegal shouldcombine diet-based strategies through production and consumption of animal derived food, vegetable, fruits and food fortification program. However, Moringa Oleifera is one example of local food that can be used in nutritional intervention program, but its use needs additional rigorous clinical trials to confirm its nutritional benefits.&nbsp

A model-based assessment of the effects of projected climate change on the water resources of Jordan

This paper is concerned with the quantification of the likely effect of anthropogenic climate change on the water resources of Jordan by the end of the twenty-first century. Specifically, a suite of hydrological models are used in conjunction with modelled outcomes from a regional climate model, HadRM3, and a weather generator to determine how future flows in the upper River Jordan and in the Wadi Faynan may change. The results indicate that groundwater will play an important role in the water security of the country as irrigation demands increase. Given future projections of reduced winter rainfall and increased near-surface air temperatures, the already low groundwater recharge will decrease further. Interestingly, the modelled discharge at the Wadi Faynan indicates that extreme flood flows will increase in magnitude, despite a decrease in the mean annual rainfall. Simulations projected no increase in flood magnitude in the upper River Jordan. Discussion focuses on the utility of the modelling framework, the problems of making quantitative forecasts and the implications of reduced water availability in Jordan

Deletion of low molecular weight protein tyrosine phosphatase (Acp1) protects against stress-induced cardiomyopathy.

The low molecular weight protein tyrosine phosphatase (LMPTP), encoded by the ACP1 gene, is a ubiquitously expressed phosphatase whose in vivo function in the heart and in cardiac diseases remains unknown. To investigate the in vivo role of LMPTP in cardiac function, we generated mice with genetic inactivation of the Acp1 locus and studied their response to long-term pressure overload. Acp1(-/-) mice develop normally and ageing mice do not show pathology in major tissues under basal conditions. However, Acp1(-/-) mice are strikingly resistant to pressure overload hypertrophy and heart failure. Lmptp expression is high in the embryonic mouse heart, decreased in the postnatal stage, and increased in the adult mouse failing heart. We also show that LMPTP expression increases in end-stage heart failure in humans. Consistent with their protected phenotype, Acp1(-/-) mice subjected to pressure overload hypertrophy have attenuated fibrosis and decreased expression of fibrotic genes. Transcriptional profiling and analysis of molecular signalling show that the resistance of Acp1(-/-) mice to pathological cardiac stress correlates with marginal re-expression of fetal cardiac genes, increased insulin receptor beta phosphorylation, as well as PKA and ephrin receptor expression, and inactivation of the CaMKIIδ pathway. Our data show that ablation of Lmptp inhibits pathological cardiac remodelling and suggest that inhibition of LMPTP may be of therapeutic relevance for the treatment of human heart failure

Computerized tumor multinucleation index (MuNI) is prognostic in p16+ oropharyngeal carcinoma

BACKGROUNDPatients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure for p16+ OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16+ OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability.METHODSWe present a deep-learning-based metric, the multinucleation index (MuNI), for prognostication in p16+ OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16+ OPSCC were acquired from 6 institutions for optimization and validation of the MuNI.RESULTSThe MuNI was prognostic for DFS, overall survival (OS), or distant metastasis-free survival (DMFS) in p16+ OPSCC, with HRs of 1.78 (95% CI: 1.37-2.30), 1.94 (1.44-2.60), and 1.88 (1.43-2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately.CONCLUSIONMuNI holds promise as a low-cost, tissue-nondestructive, H&E stain-based digital biomarker test for counseling, treatment, and surveillance of patients with p16+ OPSCC. These data support further confirmation of the MuNI in prospective trials.FUNDINGNational Cancer Institute (NCI), NIH; National Institute for Biomedical Imaging and Bioengineering, NIH; National Center for Research Resources, NIH; VA Merit Review Award from the US Department of VA Biomedical Laboratory Research and Development Service; US Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award; DOD Prostate Cancer Idea Development Award; DOD Lung Cancer Investigator-Initiated Translational Research Award; DOD Peer-Reviewed Cancer Research Program; Ohio Third Frontier Technology Validation Fund; Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering; Clinical and Translational Science Award (CTSA) program, Case Western Reserve University; NCI Cancer Center Support Grant, NIH; Career Development Award from the US Department of VA Clinical Sciences Research and Development Program; Dan L. Duncan Comprehensive Cancer Center Support Grant, NIH; and Computational Genomic Epidemiology of Cancer Program, Case Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of VA, the DOD, or the US Government

Rotational Broadening and Doppler Tomography of the Quiescent X-Ray Nova Centaurus X-4

We present high and intermediate resolution spectroscopy of the X-ray nova Centaurus X-4 during its quiescent phase. Our analysis of the absorption features supports a K3-K5V spectral classification for the companion star, which contributes approximately 75 % of the total flux at Halpha. Using the high resolution spectra we have measured the secondary star's rotational broadening to be V_rot*sin(i) = 43 +/- 6 km/s and determined a binary mass ratio of q=0.17 +/- 0.06. Combining our results for K_2 and q with the published limits for the binary inclination, we constrain the mass of the compact object and the secondary star to the ranges 0.49 < M_1 < 2.49 Msun and 0.04 < M_2 < 0.58 Msun. A Doppler image of the Halpha line shows emission coming from the secondary star, but no hotspot is present. We discuss the possible origins of this emission.Comment: 10 pages, 4 figures, accepted by MNRA

The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration

Superoxide dismutase (SOD1) gene variants may cause amyotrophic lateral sclerosis, some of which are associated with a distinct phenotype. Most studies assess limited variants or sample sizes. In this international, retrospective observational study, we compare phenotypic and demographic characteristics between people with SOD1-ALS and people with ALS and no recorded SOD1 variant. We investigate which variants are associated with age at symptom onset and time from onset to death or censoring using Cox proportional-hazards regression. The SOD1-ALS dataset reports age of onset for 1122 and disease duration for 883 people; the comparator population includes 10,214 and 9010 people respectively. Eight variants are associated with younger age of onset and distinct survival trajectories; a further eight associated with younger onset only and one with distinct survival only. Here we show that onset and survival are decoupled in SOD1-ALS. Future research should characterise rarer variants and molecular mechanisms causing the observed variability

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases.

Neurodegenerative diseases (NDs) including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease are incurable and affect millions of people worldwide. The development of treatments for this unmet clinical need is a major global research challenge. Computer-aided drug design (CADD) methods minimize the huge number of ligands that could be screened in biological assays, reducing the cost, time, and effort required to develop new drugs. In this review, we provide an introduction to CADD and examine the progress in applying CADD and other molecular docking studies to NDs. We provide an updated overview of potential therapeutic targets for various NDs and discuss some of the advantages and disadvantages of these tools

Identification and Classification of Moving Vehicles on Road

It is important to know the road traffic density real time especially in cities for signal control and effective traffic management. In recent years, video monitoring and surveillance systems have been widely used in traffic management. Hence, traffic density estimation and vehicle classification can be achieved using video monitoring systems. The image sequences for traffic scenes are recorded by a stationary camera. The method is based on the establishment of correspondences between regions and vehicles, as the vehicles move through the image sequence. Background subtraction is used which improves the adaptive background mixture model and makes the system learn faster and more accurately, as well as adapt effectively to changing environments. The resulting system robustly identifies vehicles, rejecting background and tracks vehicles over a specific period of time. Once the (object) vehicle is tracked, the attributes of the vehicle like width, length, perimeter, area etc are extracted by image process feature extraction techniques. These features will be used in classification of vehicle as big or small using neural networks classification technique of data mining. In proposed system we use LABVIEW and Vision assistant module for image processing and feature extraction.  A feed-forward neural network is trained to classify vehicles using data mining WEKA toolbox. The system will solve major problems of human effort and errors in traffic monitoring and time consumption in conducting survey and analysis of data. The project will benefit to reduce cost of traffic monitoring system and complete automation of traffic monitoring system. Keywords: Image processing, Feature extraction, Segmentation, Threshold, Filter, Morphology, Blob, LABVIEW, NI, VI, Vision assistant, Data mining, Machine learning, Neural network, Back propagation, Multi layer perception, Classification, WEK