Programming Abstractions for Data Locality

The goal of the workshop and this report is to identify common themes and standardize concepts for locality-preserving abstractions for exascale programming models. Current software tools are built on the premise that computing is the most expensive component, we are rapidly moving to an era that computing is cheap and massively parallel while data movement dominates energy and performance costs. In order to respond to exascale systems (the next generation of high performance computing systems), the scientific computing community needs to refactor their applications to align with the emerging data-centric paradigm. Our applications must be evolved to express information about data locality. Unfortunately current programming environments offer few ways to do so. They ignore the incurred cost of communication and simply rely on the hardware cache coherency to virtualize data movement. With the increasing importance of task-level parallelism on future systems, task models have to support constructs that express data locality and affinity. At the system level, communication libraries implicitly assume all the processing elements are equidistant to each other. In order to take advantage of emerging technologies, application developers need a set of programming abstractions to describe data locality for the new computing ecosystem. The new programming paradigm should be more data centric and allow to describe how to decompose and how to layout data in the memory.Fortunately, there are many emerging concepts such as constructs for tiling, data layout, array views, task and thread affinity, and topology aware communication libraries for managing data locality. There is an opportunity to identify commonalities in strategy to enable us to combine the best of these concepts to develop a comprehensive approach to expressing and managing data locality on exascale programming systems. These programming model abstractions can expose crucial information about data locality to the compiler and runtime system to enable performance-portable code. The research question is to identify the right level of abstraction, which includes techniques that range from template libraries all the way to completely new languages to achieve this goal

Magnetic resonance neurography: technical considerations

Proper performance of magnetic resonance neurography (MRN) is essential not only to make the examination easier to interpret but also for its accurate evaluation. This article outlines the technical considerations of MRN, various imaging pulse sequences available on current scanners, as well as their relative advantages and disadvantages. In addition, a guide to the optimal use of high-resolution and high-contrast MRN technique is provided, which will aid clinicians in attaining a good-quality examination

Patellofemoral friction syndrome: magnetic resonance imaging correlation of morphologic and T2 cartilage imaging

This study aimed to investigate whether patellofemoral T2 cartilage changes are associated with lateral patellofemoral friction syndrome (PFS), as indicated by an edema-like signal within the superolateral infrapatellar (Hoffa) fat pad. In this institutional review board-approved retrospective study of 510 consecutive patients, 49 patients with 50 knee magnetic resonance imaging examinations demonstrating normal or low-grade patellofemoral cartilage abnormalities (whole-organ magnetic resonance imaging score [WORMS] score, ≤2) were included. Twenty-two examinations with PFS (cases) were compared with an age- and sex-matched cohort of 28 examinations without PFS (controls). A 3-T magnetic resonance imaging was performed with multi-echo, spin-echo T2 mapping. Two readers measured in consensus malalignment parameters, including patellar height index, tibial tuberosity to trochlear groove distance, and sulcus angle. Bulk T2 cartilage values in the lateral and medial patellofemoral compartment, central weight-bearing medial and lateral femoral condyles were measured independently. Interobserver agreement was quantified using concordance correlation coefficients. Demographics, anatomic measurements, whole-organ magnetic resonance imaging scores, and cartilage T2 values were compared between cases and controls using Fisher exact test, Wilcoxon rank sum test, and mixed-effects models. Cases demonstrated higher patellar height index (P = 0.002) and tibial tuberosity to trochlear groove distance (P = 0.02). Interobserver agreement for T2 values was good overall (concordance correlation coefficient range, 0.65-0.93). Cases demonstrated higher medial facet patellar bulk T2 (38.1 [7.5] ms) versus controls (33.6 [7.3] ms) (P = 0.02); otherwise, there were no significant differences in regional T2 values. T2 mapping in patients with PFS demonstrates increased cartilage T2 in the medial patellar facet, possibly reflecting collagen alteration from early chondromalacia (softening) or increased water content related to altered contact pressures

The use of small field of view 3T MRI for identification of articular cartilage defects in the canine stifle: An ex vivo cadaveric study

Noninvasive identification of canine articular cartilage injuries is challenging. The objective of this prospective, cadaveric, diagnostic accuracy study was to determine if small field-of-view, three tesla magnetic resonance imaging (MRI) was an accurate method for identifying experimentally induced cartilage defects in canine stifle joints. Forty-two canine cadaveric stifles (n = 6/group) were treated with sham control, 0.5, 1.0, or 3.0 mm deep defects in the medial or lateral femoral condyle. Proton density-weighted, T1-weighted, fast-low angle shot, and T2 maps were generated in dorsal and sagittal planes. Defect location and size were independently determined by two evaluators and compared to histologic measurements. Accuracy of MRI was determined using concordance correlation coefficients. Defects were identified correctly in 98.8% (Evaluator 1) and 98.2% (Evaluator 2) of joints. Concordance correlation coefficients between MRI and histopathology were greater for defect depth (Evaluator 1: 0.68-0.84; Evaluator 2: 0.76-0.83) compared to width (Evaluator 1: 0.30-0.54; Evaluator 2: 0.48-0.68). However, MRI overestimated defect depth (histopathology: 1.65 ± 0.94 mm; Evaluator 1, range of means: 2.07-2.38 mm; Evaluator 2, range of means: 2-2.2 mm) and width (histopathology: 6.98 ± 1.32 mm; Evaluator 1, range of means: 8.33-8.8 mm; Evaluator 2, range of means: 6.64-7.16 mm). Using the paired t-test, the mean T2 relaxation time of cartilage defects was significantly greater than the mean T2 relaxation time of adjacent normal cartilage for both evaluators (P < 0.0001). Findings indicated that MRI is an accurate method for identifying cartilage defects in the cadaveric canine stifle. Additional studies are needed to determine the in vivo accuracy of this method

Clinical evaluation of single-shot and readout-segmented diffusion-weighted imaging in stroke patients at 3 T

Background: Diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) is most commonly performed utilizing a single-shot echo-planar imaging technique (ss-EPI). Susceptibility artifact and image blur are severe when this sequence is utilized at 3 T. Purpose: To evaluate a readout-segmented approach to DWI MR in comparison with single-shot echo planar imaging for brain MRI. Material and Methods: Eleven healthy volunteers and 14 patients with acute and early subacute infarctions underwent DWI MR examinations at 1.5 and 3T with ss-EPI and readout-segmented echo-planar (rs-EPI) DWI at equal nominal spatial resolutions. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) calculations were made, and two blinded readers ranked the scans in terms of high signal intensity bulk susceptibility artifact, spatial distortions, image blur, overall preference, and motion artifact. Results: SNR and CNR were greatest with rs-EPI (8.1±0.2 SNR vs. 6.0±0.2; P &lt;10-4 at 3T).Spatial distortions were greater with single-shot (0.23±0.03 at 3T; P &lt;0.001) than with rs-EPI (0.12±0.02 at 3T).Combined with blur and artifact reduction, this resulted in a qualitative preference for the readout-segmented scans overall. Conclusion: Substantial image quality improvements are possible with readout-segmented vs. single-shot EPI - the current clinical standard for DWI - regardless of field strength (1.5 or 3 T). This results in improved image quality secondary to greater real spatial resolution and reduced artifacts from susceptibility in MR imaging of the brai

The application of three-dimensional diffusion-weighted PSIF technique in peripheral nerve imaging of the distal extremities

To evaluate whether the addition of the three-dimensional diffusion-weighted reversed fast imaging with steady state free precession (3D DW-PSIF) sequence improves the identification of peripheral nerves in the distal extremities. Twelve MR neurography (MRN) studies of the distal upper extremity and 12 MRN studies of distal lower extremity were evaluated. From the 24 subjects who were enrolled, 10 had clinically suspected peripheral neuropathy, whereas 14 suffered from various orthopedic diseases and had no clinical signs of neuropathy. In each examination, the ability to identify each peripheral nerve on T2-weighted and 3D DW-PSIF sequences was evaluated using a semi-quantitative (0-2) scale. Thereafter, a total certainty score was registered for each sequence. Combining the results of all studies, the mean certainty score was 1.92 ± 0.28 on the 3D DW-PSIF images and 1.50 ± 0.72 on the T2-weighted images (P < 0.001). In the upper extremity studies, the corresponding certainty scores were 2.0 and 1.70 ± 0.55, respectively (P = 0.008), and in the lower extremity studies, 1.86 ± 0.35 and 1.36 ± 0.79, respectively (P < 0.001). The 3D DW-PSIF images provide improved identification of the nerves compared with the T2-weighted images, and should be incorporated in the MRN protocol, whenever accurate nerve localization and/or presurgical evaluation are required

Arsenic Trioxide Enhances the NK Cell Cytotoxicity Against Acute Promyelocytic Leukemia While Simultaneously Inhibiting Its Bio-Genesis

Natural killer cells (NK) contribute significantly to eradication of cancer cells, and there is increased interest in strategies to enhance it’s efficacy. Therapeutic agents used in the treatment of cancer can impact the immune system in a quantitative and qualitative manner. In this study, we evaluated the impact of arsenic trioxide (ATO) used in the management of acute promyelocytic leukemia (APL) on NK cell reconstitution and function. In patients with APL treated with single agent ATO, there was a significant delay in the reconstitution of circulating NK cells to reach median normal levels from the time of diagnosis (655 days for NK cells vs 145 and 265 days for T cells and B cells, respectively). In vitro experiments demonstrated that ATO significantly reduced the CD34 hematopoietic stem cell (HSC) differentiation to NK cells. Additional experimental data demonstrate that CD34+ sorted cells when exposed to ATO lead to a significant decrease in the expression of IKZF2, ETS1, and TOX transcription factors involved in NK cell differentiation and maturation. In contrast, exposure of NK cells and leukemic cells to low doses of ATO modulates NK cell receptors and malignant cell ligand profile in a direction that enhances NK cell mediated cytolytic activity. We have demonstrated that NK cytolytic activity toward NB4 cell line when exposed to ATO was significantly higher when compared with controls. We also validated this beneficial effect in a mouse model of APL were the median survival with ATO alone and ATO + NK was 44 days (range: 33–46) vs 54 days (range: 52–75). In conclusion, ATO has a differential quantitative and qualitative effect on NK cell activity. This information can potentially be exploited in the management of leukemia

Comprehensive transcriptome analysis identifies pathways with therapeutic potential in locally advanced cervical cancer

AbstractObjectiveThe objective of the present study was to provide genomic and transcriptomic information that may improve clinical outcomes for locally advanced cervical cancer (LACC) patients by searching for therapeutic targets or potential biomarkers through the analysis of significantly altered signaling pathways in LACC.MethodsMicroarray-based transcriptome profiling of 89 tumor samples from women with LACC was performed. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, significantly over-expressed genes in LACC were identified; these genes were validated by quantitative reverse transcription-polymerase chain reaction in an independent cohort, and the protein expression data were obtained from the Human Protein Atlas.ResultsA transcriptome analysis revealed 7530 significantly over-expressed genes in LACC samples. By KEGG analysis, we found 93 dysregulated signaling pathways, including the JAK-STAT, NOTCH and mTOR-autophagy pathways, which were significantly upregulated. We confirmed the overexpression of the relevant genes of each pathway, such as NOTCH1, JAK2, STAM1, SOS1, ADAM17, PSEN1, NCSTN, RPS6, STK11/LKB1 and MLTS8/GBL in LACC compared with normal cervical tissue epithelia.ConclusionsThrough comprehensive genomic and transcriptomic analyses, this work provides information regarding signaling pathways with promising therapeutic targets, suggesting novel target therapies to be considered in future clinical trials for LACC patients