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Data are limited on the ability of dipyridamole to additionally inhibit platelet function/reactivity in ischaemic cerebrovascular disease (CVD) patients on aspirin.To assess inhibition of platelet function/reactivity and platelet activation with dipyridamole in CVD.This prospective, observational study assessed TIA/ischaemic stroke patients before (baseline; N = 60), at 14 ±7 days (14d, N = 39) and ≥ 90 days (90d, N = 31) after adding dipyridamole to aspirin. Platelet function/reactivity at high shear stress (PFA-100® C-ADP) and low shear stress (VerifyNow® P2Y12 and Multiplate® ADP assays), and platelet activation status (% expression of CD62P, CD63 and leucocyte-platelet complexes on whole blood flow cytometry) were quantified. 'Dipyridamole-high on-treatment platelet reactivity (HTPR)' was defined as failure to inhibit ADP-induced platelet aggregation +/- adhesion compared with the patient's baseline on aspirin monotherapy by more than twice the coefficient-of-variation of the assay after adding dipyridamole to aspirin.Dipyridamole-HTPR was identified in 71.4-75% of patients on PFA-100 C-ADP, 83.9-86.8% of patients on VerifyNow P2Y12, and 81.5-83.3% of patients on Multiplate ADP assays. There were no changes in CD62P/CD63 expression (P ≥ 0.18), or consistent changes in leucocyte-platelet complexes in CVD patients overall at 14d or 90d vs. baseline after commencing dipyridamole. Monocyte-platelet complexes increased in the patient subgroup with dipyridamole-HTPR at 14d and 90d on PFA-100, and at 14d on VerifyNow (P ≤ 0.04), but not in those without dipyridamole-HTPR.Additional antiplatelet effects of dipyridamole are detectable under high and low shear stress conditions with user-friendly platelet function/reactivity tests ex vivo. Increasing circulating monocyte-platelet complexes over time are associated with dipyridamole-HTPR.

PURPOSE/OBJECTIVE(S) Nasopharyngeal carcinoma (NPC) is a distinct head and neck cancer that is associated with Epstein-Barr virus (EBV). Its histomorphology is characterized by epithelial carcinoma that is admixed with immune cells. This cellular pattern concurs with whole exome sequencing (WES) profiles of NPC that reveal several recurrent mutations involving NFKs and MHC-class genes, which are linked to poor outcomes. There is little information on the transcriptomic landscape of NPC. Here, we performed whole transcriptome sequencing (RNAseq) of a prospectively recruited cohort of NPC patients who were treated at a single institution. MATERIALS/METHODS Patients with biopsy-proven NPC, staged using the UICC/AJCC 8th ed, were prospectively recruited under an institutional approved protocol. All formalin-fixed paraffin-embedded specimens were centrally reviewed. Specimens with tumor cellularity of > 70% were macrodissected and Ranse (Illumina Trusses, CA) was performed. All patients underwent radiotherapy (RT); concurrent (CRT) and/or induction (IC) or adjuvant chemotherapy (AC) was performed for patients with advanced NPC. Primary clinical endpoint was disease-free survival (DFS). RESULTS Of 1,040 patients recruited, 145 patients had specimens that were successfully profiled by Ranse. Median age of this sub-cohort was 54.2 (IQR: 45.2-61.1) y; median follow-up was 4.8 (IQR: 3.3-8.1) y. Stage distribution was as such: 10 (6.9%) for Stage 1, 36 (24.8%) for Stage 2, 47 (32.4%) for Stage 3 and 41 (28.3%) for Stage 4A; 7 (4.8%) for Stage 4B; 4 (2.8%) were unclassified. 77 (53.1%) and 55 (37.9%) had EBV DNA titers of < 4,000 copies/ml and ≥4,000 copies/ml, respectively (13 [9.0%] missing). In terms of treatment received, 42 (29.0%) underwent RT alone; 50 (34.5%) and 41 (28.3%) received CRT and IC/AC+CRT; 12 (8.3%) had other treatment combinations. Unsupervised hierarchical clustering using expression of the top 1,000 most variable genes across the cohort revealed three distinct clusters that were characterized by differential expression of immune-related genes; incidentally, the cluster of patients with low immune score were enriched for recurrences, while the intermediate/high immune score groups had comparable prognoses. Subsequently, we performed gene-selection based on the low and intermediate/high immune score clusters and identified 511 genes that were significantly differentially expressed between them. We further clustered these genes to obtain a representative 5-gene GC that was prognostic for DFS (HR 3.28 [95% CI: 1.36-7.9]) on multivariable analyses, adjusted for T- and N-status and EBV DNA. Our GC was also prognostic for DFS in a validation dataset (N = 88, Zhang et al., 2017); HR 2.1 (95% CI: 0.73-6). CONCLUSION Herein, we developed and validated an immune-based prognostic GC for NPC. Our findings underscore the importance of the immune landscape in EBV-positive NPC.

Experiments have been carried out to measure the profile of the depth of a bed of sand flowing at steady state through an inclined, rotating cylinder fitted with a dam. Results are given for cylindrical and conical dams fitted at the end of the cylinder, and for cylindrical and conical internal dams, fitted halfway along the cylinder. The results are compared to the model of Saeman and of Kramers and Croockewit; the agreement is good, showing that the model is a useful predictor for flow over dams as well as for flow through cylinders without dams. The results are relevant to industrial kilns, which often contain conical brickwork dams at the discharge end and part way along the kiln.

A detailed analysis of the motion af a single particle in a slowly rotating horizontal cylinder in the avalanching mode has been carried out using the positron emission particle–tracking technique to follow the motion of a tagged particle. Cylinders of diameters 240, 390, and 488 mm, and sand of mean diameter 500 μm were used; the tracer was an irradiated sand particle. It was found that a tracer particle rotates with the bed in rigid body motion and then traverses the active surface region in a series of discrete avalanches before being absorbed once again into the rigid body rotation. The mean number of avalanches required to traverse the active region decreased from 3.5 to 4 at low rotational speed to 1 at higher rotational speed at the transition to the rolling mode.

We present a problem of commonly used characterization sequences (CS) for the protocol conformance testing and propose a new test sequence to resolve the problem. The proposed test sequence can decide whether a fault arises in the edge being tested or in edges composing the CS of the tested edge. Additionally, its fault coverage is much wider than that of other test sequence generation methods. To achieve the goal, we introduce the k-strong FSM and the extended UIO(EUIO), and show that it can be constructed from any CS. We also illustrate our technique on Q.2931, which is the call establishing protocol in B-ISDN. To increase the probability that a given FSM might be k-strong, we introduce a new test sequence generation scheme using cyclic input characterization sequence (CICS). Also, we present a technique to reduce the length of the test sequence satisfying the completeness.