Predicting and explaining the movement of mesoscale oceanographic features using CLIPS

The Naval Research Laboratory has developed an oceanographic expert system that describes the evolution of mesoscale features in the Gulf Stream region of the northwest Atlantic Ocean. These features include the Gulf Stream current and the warm and cold core eddies associated with the Gulf Stream. An explanation capability was added to the eddy prediction component of the expert system in order to allow the system to justify the reasoning process it uses to make predictions. The eddy prediction and explanation components of the system have recently been redesigned and translated from OPS83 to C and CLIPS and the new system is called WATE (Where Are Those Eddies). The new design has improved the system's readability, understandability and maintainability and will also allow the system to be incorporated into the Semi-Automated Mesoscale Analysis System which will eventually be embedded into the Navy's Tactical Environmental Support System, Third Generation, TESS(3)

Oral dosing for antenatal corticosteroids in the Rhesus macaque.

Antenatal corticosteroids (ACS) are standard of care for women at risk of preterm delivery, although choice of drug, dose or route have not been systematically evaluated. Further, ACS are infrequently used in low resource environments where most of the mortality from prematurity occurs. We report proof of principle experiments to test betamethasone-phosphate (Beta-P) or dexamethasone-phosphate (Dex-P) given orally in comparison to the clinical treatment with the intramuscular combination drug beta-phosphate plus beta-acetate in a Rhesus Macaque model. First, we performed pharmacokinetic studies in non-pregnant monkeys to compare blood levels of the steroids using oral dosing with Beta-P, Dex-P and an effective maternal intramuscular dose of the beta-acetate component of the clinical treatment. We then evaluated maternal and fetal blood steroid levels with limited fetal sampling under ultrasound guidance in pregnant macaques. We found that oral Beta is more slowly cleared from plasma than oral Dex. The blood levels of both drugs were lower in maternal plasma of pregnant than in non-pregnant macaques. Using the pharmacokinetic data, we treated groups of 6-8 pregnant monkeys with oral Beta-P, oral Dex-P, or the maternal intramuscular clinical treatment and saline controls and measured pressure-volume curves to assess corticosteroid effects on lung maturation at 5d. Oral Beta-P improved the pressure-volume curves similarly to the clinical treatment. Oral Dex-P gave more variable and nonsignificant responses. We then compared gene expression in the fetal lung, liver and hippocampus between oral Beta-P and the clinical treatment by RNA-sequencing. The transcriptomes were largely similar with small gene expression differences in the lung and liver, and no differences in the hippocampus between the groups. As proof of principle, ACS therapy can be effective using inexpensive and widely available oral drugs. Clinical dosing strategies must carefully consider the pharmacokinetics of oral Beta-P or Dex-P to minimize fetal exposure while achieving the desired treatment responses

Plaque Contact Surface Area and Flow Lumen Volume Predict Stroke Risk in Extracranial Carotid Artery Stenosis

The standard indication for intervention in asymptomatic disease is currently percent stenosis in the internal carotid artery as measured by the NASCET method, which remains limited in discriminating power. CT angiography (CTA) is widely used to calculate NASCET stenosis but also offers the opportunity to analyze carotid artery plaques from a morphological perspective that has not been widely utilized. We aim to improve stroke risk stratification of patients with carotid artery stenosis using plaque 3D modeling and image analysis. Patients with CTAs appropriate for 3D reconstruction were identified from an NIH designated stroke center database, and carotid arteries were segmented and analyzed using software algorithms to calculate contact surface area between the plaque and blood flow (CSA), and volume of the flow lumen within the region of the plaque (FLV). These novel parameters factor in the 3D morphometry inherent to each carotid plaque. A total of 134 carotid arteries were analyzed, 33 of which were associated with an ipsilateral stroke. Plaques associated with stroke demonstrated statistically significant increases in average CSA and FLV when compared to those not associated with stroke. When compared to NASCET percent stenosis, CSA and FLV both demonstrated a larger area under the receiver operating characteristics curve (AUC) in predicting stroke risk in patients with carotid stenosis. The data presented here demonstrate morphological features of carotid plaques that are independent of NASCET criteria stratification and may present an improved method in assessing stroke risk in patients with carotid artery stenosis

Measuring Thread Timing to Assess the Feasibility of Early-bird Message Delivery

Early-bird communication is a communication/computation overlap technique that combines fine-grained communication with partitioned communication to improve application run-time. Communication is divided among the compute threads such that each individual thread can initiate transmission of its portion of the data as soon as it is complete rather than waiting for all of the threads. However, the benefit of early-bird communication depends on the completion timing of the individual threads. In this paper, we measure and evaluate the potential overlap, the idle time each thread experiences between finishing their computation and the final thread finishing. These measurements help us understand whether a given application could benefit from early-bird communication. We present our technique for gathering this data and evaluate data collected from three proxy applications: MiniFE, MiniMD, and MiniQMC. To characterize the behavior of these workloads, we study the thread timings at both a macro level, i.e., across all threads across all runs of an application, and a micro level, i.e., within a single process of a single run. We observe that these applications exhibit significantly different behavior. While MiniFE and MiniQMC appear to be well-suited for early-bird communication because of their wider thread distribution and more frequent laggard threads, the behavior of MiniMD may limit its ability to leverage early-bird communication

Double-labelling immunohistochemistry for MGMT and a “cocktail” of non-tumourous elements is a reliable, quick and easy technique for inferring methylation status in glioblastomas and other primary brain tumours

BACKGROUND: Our aim was to develop a new protocol for MGMT immunohistochemistry with good agreement between observers and good correlation with molecular genetic tests of tumour methylation. We examined 40 primary brain tumours (30 glioblastomas and 10 oligodendroglial tumours) with our new technique, namely double-labelling immunohistochemistry for MGMT and a "cocktail" of non-tumour antigens (CD34, CD45 and CD68). We compared the results with single-labelling immunohistochemistry for MGMT and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA, a recognised molecular genetic technique which we applied as the gold-standard for the methylation status). RESULTS: Double-labelling immunohistochemistry for MGMT produced a visual separation of tumourous and non-tumourous elements on the same histological slide, making it quick and easy to determine whether tumour cell nuclei were MGMT-positive or MGMT-negative (and thereby infer the methylation status of the tumour). We found good agreement between observers (kappa 0.76) and within observer (kappa 0.84). Furthermore, double-labelling showed good specificity (80%), sensitivity (73.33%), positive predictive value (PPV, 83.33%) and negative predictive value (NPV, 68.75%) compared to MS-MLPA. Double-labelling was quicker and easier to assess than single-labelling and it outperformed quantitative computerised image analysis of MGMT single-labelling in terms of sensitivity, specificity, PPV and NPV. CONCLUSIONS: Double-labelling immunohistochemistry for MGMT and a cocktail of non-tumourous elements provides a "one look" method for determining whether tumour cell nuclei are MGMT-positive or MGMT-negative. This can be used to infer the methylation status of the tumour. There is good observer agreement and good specificity, sensitivity, PPV and NPV compared to a molecular gold-standard

Substructure in the Coma Cluster: Giants vs Dwarfs

The processes that form and shape galaxy clusters, such as infall, mergers and dynamical relaxation, tend to generate distinguishable differences between the distributions of a cluster's giant and dwarf galaxies. Thus the dynamics of dwarf galaxies in a cluster can provide valuable insights into its dynamical history. With this in mind, we look for differences between the spatial and velocity distributions of giant (b18) galaxies in the Coma cluster. Our redshift sample contains new measurements from the 2dF and WYFFOS spectrographs, making it more complete at faint magnitudes than any previously studied sample of Coma galaxies. It includes 745 cluster members - 452 giants and 293 dwarfs. We find that the line-of-sight velocity distribution of the giants is significantly non-Gaussian, but not that for the dwarfs. A battery of statistical tests of both the spatial and localised velocity distributions of the galaxies in our sample finds no strong evidence for differences between the giant and dwarf populations. These results rule out the cluster as a whole having moved significantly towards equipartition, and they are consistent with the cluster having formed via mergers between dynamically-relaxed subclusters.Comment: 23 pages, 6 figures, to appear in Ap

A qualitative review of implementer perceptions of the national community-level malaria surveillance system in Southern Province, Zambia

BACKGROUND: Parts of Zambia with very low malaria parasite prevalence and high coverage of vector control interventions are targeted for malaria elimination through a series of interventions including reactive case detection (RCD) at community level. When a symptomatic individual presenting to a community health worker (CHW) or government clinic is diagnostically confirmed as an incident malaria case an RCD response is initiated. This consists of a CHW screening the community around the incident case with rapid diagnostic tests (RDT) and treating positive cases with artemether-lumefantrine (AL, Coartem™) in accordance with national policy. Since its inception in 2011, Zambia’s RCD programme has relied on anecdotal feedback from staff to identify issues and possible solutions. In 2014, a systematic qualitative programme review was conducted to determine perceptions around malaria rates, incentives, operational challenges and solutions according to CHWs, their supervisors and district-level managers. METHODS: A criterion-based sampling framework based on training regime and performance level was used to select nine rural health posts in four districts of Southern Province. Twenty-two staff interviews were completed to produce English or bilingual (CiTonga or Silozi + English) verbatim transcripts, which were then analysed using thematic framework analysis. RESULTS: CHWs, their supervisors and district-level managers strongly credited the system with improving access to malaria services and significantly reducing the number of cases in their area. The main implementation barriers included access (e.g., lack of rain gear, broken bicycles), insufficient number of CHWs for programme coverage, communication (e.g. difficulties maintaining cell phones and “talk time” to transmit data by phone), and inconsistent supply chain (e.g., inadequate numbers of RDT kits and anti-malarial drugs to test and treat uncomplicated cases). CONCLUSIONS: This review highlights the importance of a community surveillance system like RCD in shaping Zambia’s malaria elimination campaign by identifying community-based infections that might otherwise remain undetected. At this stage the system must ensure it can meet growing public demand by providing CHWs the tools and materials they need to consistently carry out their work and expand programme reach to more isolated communities. Results from this review will be used to plan programme scale-up into other parts of Zambia

Aram Dorsum: an extensive mid-Noachian age fluvial depositional system in Arabia Terra, Mars

A major debate in Mars science is the nature of the early Mars climate, and the availability of precipitation and runoff. Observations of relict erosional valley networks have been proposed as evidence for extensive surface run‐off around the Noachian‐Hesperian boundary. However, these valley networks only provide a time‐integrated record of landscape evolution and thus the timing, relative timescales and intensity of aqueous activity required to erode the valleys remain unknown. Here, we investigate an ancient fluvial sedimentary system in western Arabia Terra, now preserved in positive relief. This ridge, ‘Aram Dorsum’, is flat‐topped, branching, ~ 85 km long, and particularly well‐preserved. We show that Aram Dorsum was an aggradational alluvial system and that the existing ridge was once a large river channel‐belt set in extensive flood plains, many of which are still preserved. Smaller, palaeochannel‐belts feed the main system; their setting and network pattern suggest a distributed source of water. The alluvial succession is up to 60 m thick, suggesting a formation time of 105 to 107 years by analogy to Earth. Our observations are consistent with Aram Dorsum having formed by long‐lived flows of water, sourced both locally, and regionally as part of a wider alluvial system in Arabia Terra. This suggests frequent or seasonal precipitation as the source of water. Correlating our observations with previous regional‐scale mapping shows that Aram Dorsum formed in the mid‐Noachian, making it one of the oldest fluvial systems described on Mars and indicating climatic conditions that sustained surface river flows on early Mars