Aggregation Units Research Articles

Ticagrelor versus prasugrel in patients with high on-clopidogrel treatment platelet reactivity after PCI: The ISAR-ADAPT-PF study

Patients with high on-treatment platelet reactivity (HTPR) on clopidogrel are at high risk for adverse cardiovascular events after percutaneous coronary intervention (PCI). The aim of the ISAR-ADAPT-PF study was to assess the antiplatelet efficacy of ticagrelor versus prasugrel in patients with HTPR on clopidogrel. In a prospective and randomized clinical study, 70 patients with HTPR on clopidogrel loading dose (LD) within 24 h post PCI were assigned to receive either ticagrelor [180 mg LD followed by 90 mg maintenance dose (MD) twice daily] or prasugrel (60 mg LD followed by 10 mg MD once daily). The adenosine diphosphate-induced platelet aggregation assessed on the Multiplate analyzer on day 2 after randomization (primary end point) was as follows: the mean difference between the two treatment groups was 6 aggregation units (AU) × min with an upper 95% confidence interval (CI) of 41 AU × min, which was greater than the predefined noninferiority margin of 18 AU × min (P for noninferiority = 0.29). However, no significant differences in absolute platelet reactivity levels between ticagrelor- versus prasugrel-treated patients at that time point were observed (138 ± 100 AU × min vs. 132 ± 64 AU × min, P for superiority = 0.77). In conclusion, neither drug was statistically more effective for inhibition of platelet aggregation in patients with HTPR on clopidogrel post PCI, although the study could not formally demonstrate the assumed noninferiority of ticagrelor versus prasugrel.

Aggregation Bias in Benchmarking: Measuring Potential Process Efficiency

This paper shows that the use of excessively aggregated organizational units in a benchmarking study may skew the evaluation. The most aggregated or consolidated units receive excessively harsh evaluations. The paper also proposes a method for compensating the possible consolidation bias by calculating the so-called Potential Process Efficiency PPE. Finally,the paper applies the proposed method to the benchmarking model used by the Brazilian Electricity Regulatory Agency (ANEEL). Because of the size of the Brazilian DSOs and the heterogeneity of their service areas, it is highly likely that many of the DSOs are in fact subject to biased evaluations.

Accounting for Noise in the Microfoundations of Information Aggregation

This paper shows that the basic unit of information aggregation described by the Geanakoplos and Polemarchakis (1982) posterior revision process does not always produce public statistics that are closer to the full information posterior than the common prior. I study this process of back and forth communication between two individuals with private signals by introducing white noise into payoff computations, defining the evolution of common knowledge, and providing conjectures on the resulting public statistics. I then develop a computational method to ex-ante rank information structures on their tolerance to noise. Subjects' behavior in a laboratory experiment is consistent with the model's prediction: though the posterior revision process do move reports towards each other and towards the full information posterior, noise persists and aggregation is incomplete. As predicted, aggregation attempts in the two least noise-tolerant information structures result in public statistics that perform worse than the common prior.

MEMORY-Based Hardware Architectures to Detect ClamAV Virus Signatures with Restricted Regular Expression Features

We aim to implement a single-chip hardware detection engine for virus scanning. Our study is based on the ClamAV virus database, which contains 88.9K strings and 9.6K extended hex-signatures with restricted regular expression (regex) features. We have previously presented cost-effective hardware architectures to detect the 88.9K strings and 3.2K regex patterns that are composed of multiple string segments. In this paper, we shall present hardware architectures to detect the remaining 6.4K regex patterns. Our method is based on the information reduction approach. We transform the byte-oriented matching problem to a token-based matching problem. A regex pattern contains one or more segments, and a segment may be subdivided into multiple non-trivial tokens. In general, a token is associated with one or a few regexes only. The input byte-stream is converted into a token-stream using dedicated hardware units, where the number of tokens is much less than the number of bytes. The token-stream is processed by a NFA-based aggregation unit to determine if any segment can be found. Detected segments are further processed by a scoreboard to determine if any multi-segment pattern can be found. For proof-of-concept, our method is implemented on a Virtex-6 FPGA which consumes 1.84 MB on-chip memory.

Spatial patterns and temporal dynamics of urban bicycle crashes—A case study from Salzburg (Austria)

Most bicycle crash analyses are designed as explanatory studies. They aim to identify contributing risk factors and calculate risk rates based on – most of the time – highly aggregated statistical data. In contrast to such explanatory study designs, the presented study follows an exploratory approach, focusing on the absolute number of crashes. The aim is to reveal and describe patterns and dynamics of urban bicycle crashes on various spatial scale levels and temporal resolutions through a multi-stage workflow. Spatial units are delineated in the network space and serve as initial units of aggregation. In order to facilitate comparisons among regions and quantify temporal dynamics, a reference value of crash frequency is simulated for each unit of the respective spatial scale level and temporal resolution.For the presented case study, over 3000 geo-coded bicycle crashes in the city of Salzburg (Austria) were analyzed. The data set covers 10years and comprises all bicycle crashes reported by the police. Distinct spatial and temporal patterns with clusters, seasonal variations, and regional particularities could be revealed. These insights are indicators for urban dynamics in the transport system and allow for further, targeted in-depth analyses and subsequent counter measures. Moreover, the results prove the applicability of the proposed multi-stage workflow and demonstrate the added value of analyses of small aggregates on various scale levels, down to single crashes, and temporal resolutions.

Performance evaluation of cognitive radio in advanced metering infrastructure communication

Smart grid is an intelligent electricity grid system. A reliable two-way communication system is required to transmit both critical and non-critical smart grid data. However, it is difficult to locate a huge chunk of dedicated spectrum for smart grid communications. Hence, cognitive radio based communication is applied. Cognitive radio allows smart grid users to access licensed spectrums opportunistically with the constraint of not causing harmful interference to licensed users. In this paper, a cognitive radio based smart grid communication framework is proposed. Smart grid framework consists of Home Area Network (HAN) and Advanced Metering Infrastructure (AMI), while AMI is made up of Neighborhood Area Network (NAN) and Wide Area Network (WAN). In this paper, the authors only report the findings for AMI communication. AMI is smart grid domain that comprises smart meters, data aggregator unit, and billing center. Meter data are collected by smart meters and transmitted to data aggregator unit by using cognitive 802.11 technique; data aggregator unit then relays the data to billing center using cognitive WiMAX and TV white space. The performance of cognitive radio in AMI communication is investigated using Network Simulator 2. Simulation results show that cognitive radio improves the latency and throughput performances of AMI. Besides, cognitive radio also improves spectrum utilization efficiency of WiMAX band from 5.92% to 9.24% and duty cycle of TV band from 6.6% to 10.77%.

A DNA-Based Building Block for Designer Excitonic Circuits

Mimicking the ability of natural light harvesting systems to absorb and transport energy efficiently over long ranges is an important unmet challenge in bionanotechnology. Structured biomolecular scaffolds such as DNA assemblies offer exquisite control over 3D nanometer-scale chromophore organization to program custom energy transfer pathways at the nanoscale while exploiting the quantum nature of inter-molecular chromophore coupling. Here, we report a bottom-up multi-chromophore design framework that leverages quantum properties to design modular, customizable excitonic circuits using programmed DNA assemblies. To achieve this we employ sequence-specific DNA scaffolds that organize strongly interacting cyanine aggregates as building blocks to construct fast, coherent energy transfer in complex supramolecular architectures. Using this approach, we synthesized a DX-tile that consists of multiple interacting cyanine aggregate units to attain spectral tunability, superradiance and fast exciton transport. Because of the increasing number of synthetic chromophores available and the structural flexibility and control of programmable DNA nanotechnology, our bottom-up approach may enable rational design of a broad array of nanoscale excitonic circuits in large-scale one-, two-, and three-dimensional DNA-based arrays.

Randomized Comparison of Different Thienopyridine Loading Strategies in Patients Undergoing Elective Coronary Intervention: The ExcelsiorLOAD Trial.

This randomized trial investigated to what extent loading with prasugrel can provide a more rapid peri-interventional antiplatelet effect than clopidogrel 600 mg. Effective platelet inhibition at the start of a percutaneous coronary intervention (PCI) reduces the risk of ischemic complications. With clopidogrel administered immediately before a PCI, effective platelet inhibition is delayed by 2 h. Prasugrel has the potential of shortening this period. We randomly assigned 300 P2Y12 receptor blocker-naive patients undergoing an elective PCI to loading with clopidogrel 600 mg, prasugrel 30 mg, or prasugrel 60 mg immediately before the PCI. Platelet function was assessed serially by impedance aggregometry. The primary endpoint was the proportion of patients with high on-treatment platelet reactivity at 60 min after loading defined as ≥468 aggregation units × minute (Multiplate Analyzer, Roche Diagnostics, Mannheim, Germany). The 3 groups were well balanced with respect to clinical and angiographic characteristics. At 60 min, 33% of the patients assigned to prasugrel 60 mg, 37% of patients assigned to prasugrel 30 mg, but 55% of those assigned to clopidogrel had high on-treatment platelet reactivity (p < 0.001). At any time point starting from 30 min, prasugrel 60 mg achieved significantly lower platelet reactivity than clopidogrel. Platelet reactivity at 60 min after prasugrel was not significantly different from that at 120 min after clopidogrel (p = 0.18). Prasugrel 30 mg had an intermediate effect. The 30-day incidence of bleeding events was not different among the 3 groups. From 30 min onward, prasugrel 60 mg achieved a stronger platelet inhibition than clopidogrel loading in stable patients undergoing a PCI. Compared with clopidogrel, prasugrel 60 mg was associated with a twice as fast onset of platelet inhibition. (Impact of Extent of Clopidogrel-Induced Platelet Inhibition during Elective Stent Implantation on Clinical Event Rate-Advanced Loading Strategies [ExcelsiorLOAD]; DRKS00006102).

Crossing the Boundaries: An Implementation of Two Methods for Projecting Data across Boundary Changes

Much of the data used in social science is aggregated into spatial units, even if the analysis itself does not explicitly incorporate that information. A key concern with such aggregation, however, is that changes in the units of aggregation themselves cause difficulty in comparing data gathered on the old boundaries and the new boundaries. Such changes present serious concerns to researchers who may exclude observations or cases due to a lack of comparable units or omit certain key variables. While geographers have long examined this problem and created methods of projecting data from one spatial unit into another, known as areal interpolation, it is telling that a recent article notes the difficulty for researchers in implementing even the most basic solutions without relying heavily on programming skills or proprietary software.

Function Aggregation of New Heavy Load High Voltage Circuit Breaker Based on Axiomatic Design

To unify the design process of complex products to meet higher function and performance demands, a practical implementation for a new heavy load high voltage circuit breaker is presented. This paper analyzes the function and performance of a new heavy load high voltage circuit breaker, and addressed needs of being quick, accurate and stable. The superiority of the physical functional basis description method over the traditional functional basis model was demonstrated. The axiomatic design theory is described systematically and in detail using the function decomposition of the high voltage circuit breaker as an example. The concept of functional aggregation unit as the extension and expansion of axiomatic design theory is presented. This aggregation unit extracts essential characteristics of function and performance separately from their concrete structures, avoiding limits of the spring operating mechanism structure caused by reliance on a conventional structure. This function aggregation design method is presented for the design of a transmission unit. These results are of great theoretical significance to guide product innovation based on functional aggregation in axiomatic design theory.

Enhanced BlockACK method for A‐MPDU transmission in IEEE 802.11n/ac/ad WLANs

An enhanced block acknowledgement (BlockACK) method for the aggregate MAC protocol data unit (A-MPDU) transmission is proposed. In the proposed method, the position information of each aggregated subframe is carried by the A-MPDU using the reserved bits and a novel position information control is used to acknowledge the A-MPDU. By utilising the enhanced BlockACK method, the aggregation level of the A-MPDU transmission will not be constrained by the effect of lost subframes. Theoretical analysis and simulation results demonstrate that the enhanced BlockACK method can achieve a more stable aggregation level and higher throughput than the conventional one.

Mesoscale aggregation properties of C60 in toluene and chlorobenzene.

The mesoscale aggregation properties of C60 in two distinct aromatic solvents (toluene and chlorobenzene) and a practical range of concentrations (c = 1-2 and c = 1-5 mg mL(-1), respectively) were systematically explored by static/dynamic light scattering (SLS/DLS), small angle X-ray scattering (SAXS), depolarized dynamic light scattering (DDLS), and cryogenic transmission electron microscopy (cryo-TEM) analyses. The central observations were as follows: (1) aggregate species of sizes in the range of several hundred nanometers have been independently revealed by SLS, DLS, and DDLS analyses for both solvent systems. (2) DDLS and cryo-TEM measurements further revealed that while C60 clusters are notably anisotropic (rod-like) in chlorobenzene, they are basically isotropic (spherical) in toluene. (3) Detailed analyses of combined SLS and SAXS profiles suggested that varied, yet self-similar, solvent-induced aggregate units were responsible for the distinct (mesoscale) aggregation features noted above. (4) From a dynamic perspective, specially commissioned DLS measurements ubiquitously displayed two relaxation modes (fast and slow mode), with the second (slow) mode being q (wave vector) independent. While the fast mode in both solvent systems was basically diffusive by nature and leads to geometrical features in good agreement with the above static analyses, the slow mode was analyzed and tentatively suggested to reflect the effect of mutual confinement. (5) Micron-scale aggregate morphology of drop-cast thin films displays similar contrasting features for the two solvent media used. Overall, this study suggests that solvent-induced, nanoscale, aggregate units may be a promising factor to control a hierarchy of microscopic aggregation properties of C60 solutions and thin films.

Biochemical classification of tauopathies by immunoblot, protein sequence and mass spectrometric analyses of sarkosyl-insoluble and trypsin-resistant tau.

Intracellular filamentous tau pathology is the defining feature of tauopathies, which form a subset of neurodegenerative diseases. We have analyzed pathological tau in Alzheimer’s disease, and in frontotemporal lobar degeneration associated with tauopathy to include cases with Pick bodies, corticobasal degeneration, progressive supranuclear palsy, and ones due to intronic mutations in MAPT. We found that the C-terminal band pattern of the pathological tau species is distinct for each disease. Immunoblot analysis of trypsin-resistant tau indicated that the different band patterns of the 7–18 kDa fragments in these diseases likely reflect different conformations of tau molecular species. Protein sequence and mass spectrometric analyses revealed the carboxyl-terminal region (residues 243–406) of tau comprises the protease-resistant core units of the tau aggregates, and the sequence lengths and precise regions involved are different among the diseases. These unique assembled tau cores may be used to classify and diagnose disease strains. Based on these results, we propose a new clinicopathological classification of tauopathies based on the biochemical properties of tau.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-015-1503-3) contains supplementary material, which is available to authorized users.

Antiplatelet Efficacy of Fixed-Dose Aspirin-Clopidogrel Combination in Patients with Stable Coronary Artery Disease Treated with Drug-Eluting Stent Implantation.

A fixed-dose combination (FDC) of aspirin and clopidogrel bisulfate may improve medication adherence. However, the absence of data on the relative antiplatelet efficacy of FDC and separate dual pills (SDP) of aspirin and clopidogrel in real-world patients with stable coronary artery disease is a major factor retarding clinical introduction of such an FDC. This was a single-centre, randomized, open-label, parallel-group, non-inferiority trial. Patients who maintained a regimen of separate aspirin and clopidogrel pills for at least 1year after drug-eluting stent implantation without adverse events were enrolled. Patients were randomly assigned to either the FDC group or the SDP group. Antiplatelet efficacy and tolerability were assessed at baseline and at 4weeks. Of the 93 enrolled patients, 83 (FDC group: n=42; SDP group: n=41) completed the study. The difference in the changes in P2Y12 percentage inhibition did not exceed the predetermined value for inferiority [mean difference -1.7; 95% confidence interval (CI) -6.9 to 4.5, p<0.001 for non-inferiority]. The changes from baseline to 4weeks in P2Y12 reaction units (PRU) (mean difference 9.7PRU, p=0.46), maximal platelet aggregation (mean difference 2.0%, p=0.44) and aspirin reaction units (ARU) (mean difference -2.3ARU, p=0.88) did not differ significantly between the treatment groups. The tolerability of the FDC formulation was similar to that of SDP therapy (p=0.68). In patients with prior percutaneous coronary intervention, the antiplatelet efficacy of the aspirin/clopidogrel FDC was non-inferior to that of SDP and the tolerability of the two regimens was similar after 4weeks of treatment.

Changes in platelet function independent of pharmacotherapy following coronary intervention in non-ST-elevation myocardial infarction patients

BackgroundHigh on treatment platelet reactivity (HTPR) is common in patients receiving clopidogrel following an acute coronary syndrome (ACS); it's also associated with increased morbidity and mortality. More potent and predictable antiplatelet drugs have addressed this issue at the expense of increased bleeding. Identification of HTPR and the targeted use of more potent antiplatelet drugs has, so far, broadly failed. We investigate this approach in terms of the timing of platelet function testing and how this can impact on the ability of these bedside tests to predict HTPR around the time of coronary intervention. MethodsHigh risk ACS patients treated with 5 days of clopidogrel had platelet function assessed using the multiple electrode aggregometry system (MEA) pre, post and 24 h following percutaneous coronary intervention (PCI). Simultaneous detailed analysis of platelet status was undertaken with quantification of platelet bound and soluble p-selectin and mass spectrometry quantification of the eicosanoid 12-HETE. ResultsAs assessed by MEA 40.5% of patients had HTPR pre-PCI; mean aggregation units (AU) in response to ADP were 499.1 ± 46.3 pre-PCI, 407.6 ± 37.7 post-PCI and 269.1 ± 24.6 AU 24 h post-PCI (pre to post PCI p > 0.05, pre to 24 h post-PCI p = 0.0002). This highly significant drop in platelet reactivity was contrasted with on-going expression of platelet bound p-selectin, increased soluble p-selectin and rising 12-HETE concentrations. ConclusionsThis study outlines significant changes in ex-vivo platelet aggregation that occur within 24 h of PCI in high risk NSTEMI patients using bedside PFT. Whilst there were no changes in antiplatelet therapy during the study period its clear that timing is crucial when assessing high on treatment residual platelet activity.

Commentary on the 2015 SPR Standards of Evidence.

We comment on the 2015 Society for Prevention Research standards of evidence document, summarizing major changes from the previous 2005 Standards, and point to ways in which the Standards could be further improved. We endorse important new standards, such as those on testing the causal theory and mechanisms of the intervention, improved trial reporting standards, and added attention to scale-up research and cost analyses. Despite discussion of replication in the new Standards, we are concerned about the lack of stand-alone replication standards, and the deletion of an explicit requirement for replication before an intervention is considered efficacious. Finally, we are deeply concerned about the lack of attention to the unit or level of aggregation of the intervention target. It is a major conceptual oversight. The unit targeted by an intervention (whether a cell, person, organization, community, state, nation) is a fundamental feature shaping intervention theory, research design, data collection, analyses, effect sizes, diffusion possibilities and patterns, and scale-up issues. Future Standards updates should eliminate the implicit assumption in the current text that effective preventive interventions inherently target individual persons.

Ranking Method Based on Cross-efficiency and Aggregate Units in Data Envelopment Analysis

In this study a new method is developed for ranking all type of efficient decision making units (extreme and non-extreme ones) which is based on cross-efficiency aggregate units. Also, this study is able to encountering alternatives in order to find the best solutions among alternatives.

Mean platelet volume and high-residual platelet reactivity in patients receiving dual antiplatelet therapy with clopidogrel or ticagrelor

Objective: High on-treatment platelet reactivity (HRPR) is associated with a two- to ninefold increased risk of recurrent ischemic events among patients receiving dual antiplatelet therapy (DAPT) for coronary artery disease. However, its determinants are still poorly understood. The aim of the present study was to assess the impact of mean platelet volume (MPV) on platelet reactivity in patients receiving DAPT after an acute coronary syndrome or PCI.Methods: Patients treated with DAPT (acetylsalicylic acid [ASA] and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30 – 90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test > 862 aggregation units (AU)*min (for ASA) and ADP test values ≥ 417 AU*min (for ADP-antagonists).Results: Our population is represented by a total of 487 patients on DAPT, divided according to MPV tertiles (< 10.4 fl; 10.4 – 11.29 fl; ≥ 11.3 fl). Larger-sized platelets were associated with use of statins (p < 0.001) and beta-blockers (p = 0.03), higher hemoglobin levels (p = 0.002) and lower platelets count (p < 0.001). Higher platelet reactivity was observed at ASPI test in patients with higher MPV (r = 0.12, p = 0.008), but not for ADP-mediated aggregation (r = -0.007, p = 0.88). However, a low prevalence of HRPR was observed with ASA, with no impact of MPV tertiles (1.2 vs 1.1 vs 1.6%, p = 0.70, adjusted OR [95% CI] = 1.05 [0.51 – 1.77], p = 0.87). MPV did not influence the prevalence of HRPR for ADP-antagonists (25.9 vs 1 vs 26.5%, p = 0.89; adjusted OR [95% CI] = 1.1 [0.84 – 1.45], p = 0.50) with similar results among the 259 patients receiving clopidogrel (adjusted OR [95% CI] = 1.15 [0.82 – 1.62], p = 0.43) and the 228 patients on ticagrelor (adjusted OR [95% CI] = 1.46 [0.84 – 2.55], p = 0.18).Conclusion: In patients receiving DAPT, MPV does not affect the response to major antiplatelet therapies. In fact, MPV elevation does not influence the risk of HRPR with clopidogrel, ticagrelor or ASA.

Geographic variation in fasciotomy during operative management of tibia fractures

BackgroundDiagnosis and treatment of acute or impending compartment syndrome (ACS) remains a clinical challenge. ACS is a clinical diagnosis, and may be associated with variation in its definition, as well as individual threshold for fasciotomy. We examined regional and state variation in rates of lower extremity fasciotomy associated with operatively managed tibia fractures. MethodsA total of 313,344 surgically treated tibia fractures were identified via Current Procedural Terminology (CPT) codes using PearlDiver, a private-payer medical record database. Data from the PearlDiver database was compared to the National Trauma Data Bank trauma registry data to corroborate calculated fasciotomy rates. ResultsThe aggregate United States fasciotomy rate derived from PearlDiver was 2.57%. State fasciotomy rates were wide-ranging (0.03%–11.86%) with an average state rate of 2.22% (n=47, SD=2.27). ConclusionsThere was significant state-to-state variation in the use of fasciotomy during operative management of tibial fractures. Various factors may have contributed to the observed difference of state fasciotomy rates. Level of evidenceThis is a Level III epidemiological study retrospectively comparing geographic rates of fasciotomy during operative management of tibia fractures.

Dilation Effects in FRP-Confined Square Concrete Columns Using Stone, Brick, and Recycled Coarse Aggregates

AbstractThe axial capacity enhancement of square plain concrete columns due to fiber-reinforced polymer (FRP) wrap is measured through experiments as a function of the fundamental dilation property of the parent concrete. To this end, unconfined (control) and FRP-confined concrete column specimens made using stone, brick, recycled stone, and recycled brick aggregates having their own dilation properties were subjected to uniaxial compression. The dilation effect measured using the digital image correlation technique (DICT) was observed to have a distinct relation with the concrete modulus of elasticity resulting from the coarse aggregate unit weight and absorption capacities. Relations between the strengthening ratio and strain enhancement ratio with the actual confinement ratio were plotted to measure the confinement effectiveness coefficients and strain enhancement coefficients using a redefined confining pressure model. The measured coefficients are found to be distinctly lower for brick and recycled a...