Block Definition Research Articles

Ultrasound and Review of Evidence for Lower Extremity Peripheral Nerve Blocks

This qualitative systematic review summarizes existing evidence from randomized controlled trials (RCTs) comparing ultrasound (US) to alternative techniques for lower extremity peripheral nerve block. There were 11 RCTs of sufficient quality for inclusion. Jadad scores ranged from 1 to 4 with a median of 3. For femoral nerve blocks, US provided shorter onset and improved quality of sensory and motor block, as well as a decrease in local anesthetic requirements. For sciatic nerve blocks, US resulted in a higher percentage of patients with complete sensory and motor block, as well as decreased local anesthetic requirements. In 2 of the studies for sciatic nerve block, US resulted in a shorter time to successfully complete the procedure. No study was powered to detect a difference in surgical block success. Overall, there was significant heterogeneity in the definitions of successful sensory and motor block. In 2 studies, the optimal peripheral nerve stimulation technique may have not been used, resulting in a potential bias. No RCT reported US as inferior to alternative techniques in any outcome. There is level Ib evidence to make a grade A recommendation that US guidance provides improvements in onset and success of sensory block, a decrease in local anesthetic requirements, and decreased time to perform lower extremity peripheral nerve blocks.

Single nucleotide polymorphisms and the linkage disequilibrium at the LDL receptor gene in Koreans

The low-density lipoprotein (LDL) receptor gene is one of the important genes in cardiovascular biology, but gives difficulty in single nucleotide polymorphism (SNP) marker choice. Twelve SNPs at the LDL receptor locus were genotyped in 117 Korean individuals. Six SNPs (rs8111982, rs12983082, rs1003723, rs5925, rs6413504, and rs2738464) were polymorphic in the Korean sample. And 8 SNPs (rs5931, rs811 1982, rs12983082, rs11669576, rs1003723, rs5925, rs641 3504, and rs2738464) were polymorphic in at least one population among the five ethnic groups (European: CEU; Chinese: CHB; Japanese: JPT; African:YRI; and Korean: KOR). Phylogenetic trees constructed based on the twelve SNPs showed a pattern clustering KOR with CHB and JPT as more closely related than either YRI or CEU. The plot of the pairwise linkage disequilibrium (LD) values for the exon 13 SNP (rs5925) against the physical distances between pairs of SNPs showed a tendency of LD decrease in the upstream of rs5925, while the low r2 values are present in the downstream of rs5925 (≥0.20). The three SNPs (rs12983082, rs1003723, and rs5925) which are ethnically polymorphic are likely to be useful SNP markers for the LDL receptor locus. The interblock region between exon 13 and exon 18 delimited by the less stringent block definition (four gamete rule) contains a feasible recombination hotspot in the LDL receptor gene in Koreans.

Superfast Multifrontal Method for Large Structured Linear Systems of Equations

In this paper we develop a fast direct solver for large discretized linear systems using the supernodal multifrontal method together with low-rank approximations. For linear systems arising from certain partial differential equations such as elliptic equations, during the Gaussian elimination of the matrices with proper ordering, the fill-in has a low-rank property: all off-diagonal blocks have small numerical ranks with proper definition of off-diagonal blocks. Matrices with this low-rank property can be efficiently approximated with semiseparable structures called hierarchically semiseparable (HSS) representations. We reveal the above low-rank property by ordering the variables with nested dissection and eliminating them with the multifrontal method. All matrix operations in the multifrontal method are performed in HSS forms. We present efficient ways to organize the HSS structured operations along the elimination. Some fast HSS matrix operations using tree structures are proposed. This new structured multifrontal method has nearly linear complexity and a linear storage requirement. Thus, we call it a superfast multifrontal method. It is especially suitable for large sparse problems and also has natural adaptability to parallel computations and great potential to provide effective preconditioners. Numerical results demonstrate the efficiency.

LD-Spline: Mapping SNPs on genotyping platforms to genomic regions using patterns of linkage disequilibrium

BackgroundGene-centric analysis tools for genome-wide association study data are being developed both to annotate single locus statistics and to prioritize or group single nucleotide polymorphisms (SNPs) prior to analysis. These approaches require knowledge about the relationships between SNPs on a genotyping platform and genes in the human genome. SNPs in the genome can represent broader genomic regions via linkage disequilibrium (LD), and population-specific patterns of LD can be exploited to generate a data-driven map of SNPs to genes.MethodsIn this study, we implemented LD-Spline, a database routine that defines the genomic boundaries a particular SNP represents using linkage disequilibrium statistics from the International HapMap Project. We compared the LD-Spline haplotype block partitioning approach to that of the four gamete rule and the Gabriel et al. approach using simulated data; in addition, we processed two commonly used genome-wide association study platforms.ResultsWe illustrate that LD-Spline performs comparably to the four-gamete rule and the Gabriel et al. approach; however as a SNP-centric approach LD-Spline has the added benefit of systematically identifying a genomic boundary for each SNP, where the global block partitioning approaches may falter due to sampling variation in LD statistics.ConclusionLD-Spline is an integrated database routine that quickly and effectively defines the genomic region marked by a SNP using linkage disequilibrium, with a SNP-centric block definition algorithm.

Numerical Analysis of the 650,000 m2 Åknes Rock Slope based on Measured Displacements and Geotechnical Data

The unstable 650,000 m2 Aknes rock slope (Western Norway) poses a hazard, as a sudden failure may cause a destructive tsunami in the fjord. In this study the slope was divided into blocks based on displacements measured at the slope surface. Discontinuous deformation analysis (DDA) showed that three or four blocks in the upper half may be considered as potential subareas that may fail catastrophically. The lower half may be divided into two or three blocks, but more limited data introduces more uncertainty into block definition. The Universal Distinct Element code (UDEC) was used for two-dimensional (2D) stability analyses. By varying fracture geometry, fracture friction, and groundwater conditions within reasonable limits based on site-specific data a number of possible models were compared. The conclusions show that models that were unstable to great depths were in closer agreement with shear strength parameters derived from an earlier study than models that were unstable to smaller depths. The length (depth) of the outcropping fracture, along which shear displacements are shown to occur, plays an important role. A (shallow) slide at 30 m, in which displacements have been documented by borehole measurements, will reduce the stability at greater depths. Increased groundwater pressure is demonstrated to be less critical for very deep slope instability. The results of the DDA and UDEC modelling will be useful for planning of future investigations, interpretation of the subsequent results, further development of the early warning system and in the tsunami modelling.

Fields of definition of building blocks

We investigate the fields of definition up to isogeny of the abelian varieties known as building blocks. These varieties are defined as the $\mathbb {Q}$-varieties admitting real or quaternionic multiplications of the maximal possible degree allowed by their dimensions (cf. Pyle (2004)). The Shimura-Taniyama conjecture predicts that every such variety is isogenous to a non-CM simple factor of a modular Jacobian $J_1(N)$. The obstruction to descend the field of definition of a building block up to isogeny is given by Ribet in 1994 as an element in a Galois cohomology group. In this paper we begin by studying these elements from an abstract Galois-cohomological point of view, and obtain results and formulas for the computation of invariants related to them. When considered for the element attached to a building block, these invariants give the structure of its endomorphism algebra, and also complete information on the possible fields of definition up to isogeny of this building block. We implemented these computations in Magma for building blocks given as $\overline {\mathbb {Q}}$-simple factors up to isogeny of the Jacobian of the modular curve $X_1(N)$. Using this implementation we computed a table for conductors $N\leq 500$, which is described in the last section. This table is a source of examples of building blocks with different behaviors and of statistical information; in particular, it contains many examples that answer a question posed by Ribet in 1994 on the existence of a smallest field of definition up to isogeny for RM-building blocks of even dimension.

A Conceptual Framework for the Collaborative Modeling of Networked Manufacturing Systems

A manufacturing system is a product, and has to be designed as any other product. Therefore, a need for adequate methodological support and tools for modeling, structuring, and control of the next generation manufacturing systems is recognized. In this study, the adaptive distributed modeling framework for collaborative design and operations of network manufacturing systems is presented. In manufacturing networks, several autonomous partners participate in dynamic design of a manufacturing system, its implementation, and adaptation. In this context collaborative modeling, structuring, and control in distributed manufacturing environment play a vital role. The proposed modeling framework introduces the common modeling space and enables a collaborative definition of modeling building blocks, model design, simulation, and operations support of distributed manufacturing systems in a dynamic environment — which is the realistic nature of the global manufacturing. The prototype of the framework is elaborated in a case study.

Value of Diagnostic Lumbar Selective Nerve Root Block: A Prospective Controlled Study

Although diagnostic lumbar selective nerve root blocks are often used to confirm the pain-generating nerve root level, the reported accuracy of these blocks has been variable and their usefulness is controversial. The purpose of this study was to evaluate the accuracy of diagnostic lumbar selective nerve root blocks to analyze potential causes of false results in a prospective, controlled, single-blinded manner. A total of 105 block anesthetics were performed under fluoroscopic guidance in 47 consecutive patients with pure radiculopathy from a single confirmed level: 47 blocks were performed at the symptomatic level, and 58 were performed at the adjacent asymptomatic "control" level. Contrast and local anesthetics were injected, and spot radiographs were taken in all cases. We calculated the diagnostic value of the block anesthetics using concordance with the injected level. We analyzed the potential causes of false results using spot radiographs. On the basis of a definition of a positive block as 70% pain relief, determined by receiver-operator characteristic (ROC) analysis, diagnostic lumbar selective nerve root block anesthetics had a sensitivity of 57%, a specificity of 86%, an accuracy of 73%, a positive predictive value of 77%, and a negative predictive value of 71%. False-negatives were due to the following causes identifiable on spot radiographs: insufficient infiltration, insufficient passage of the injectate, and intraepineural injections. On the other hand, false-positives resulted from overflow of the injectate from the injected asymptomatic level into either the epidural space or symptomatic level. The accuracy of diagnostic lumbar selective nerve root blocks is only moderate. To improve the accuracy, great care should be taken to avoid inadequate blocks and overflow, and to precisely interpret spot radiographs.

Case-Control Study Using Array-Based Genotyping Produced a Panel of Genes Associated with Risk to Acute Myelogenous Leukemia (AML).

Multiple loci with small genetic effects are thought to be linked to AML pathogenesis. To detect such loci requires systematic screening of large number of single nucleotide polymorphisms (SNPs) within large study population. In this study we tested whether 3104 SNPs in 200 candidate genes were associated with risk to AML. Genes were considered potential candidates for their known or suspected roles in DNA repair system, pharmacogenomics and transcriptional regulation in hematopoiesis or putative pathways related to leukemogenesis. Selection of SNPs was performed using dbSNP and HapMap project databases, with emphasis on non-synonymous SNPs or haplotype tagging SNPs. To discover potential SNPs responsible for AML susceptibility, we conducted a case-control study using Affymetrix targeted genotyping 3K array. We applied this platform to analyze the samples from 309 de novo AML patients and 382 healthy controls. Genotype scorings were processed using GeneChip scanner 3000 TG(Affymetrix) and analyzed with GCOS software(Affymetrix). In total more than 255,000 SNPs were genotyped for this study. Samples with suboptimal call rates were excluded. Statistical testing were carried out using χ2, Cochran-Armitage trend, Fisher's exact, odds ratio, haplotype estimation, LD block definition. Here we report that 23 SNPs in 16 genes are associated with elevated or reduced risk to AML. Some of associated genes were transcription factors such as ZNF23 and ZNF233. While associated genes were distributed evenly among the whole genome, four associated genes were found on chromosome 1. Among those associated SNPs, two were located in coding region, one in exon-intron boundary, while the rest of SNPs were located in introns of associated genes. Among 23 SNPs identified, two intronic SNPs from 1st intron of BAALC(Brain and acute leukemia, cytoplasmic) gene were associated with the reduced risk to AML. Haplotype estimation and linkage disequilibrium pattern of 9 SNPs including two associated SNPs will be presented. In conclusion, we identified SNPs responsible for AML susceptibility by candidate gene-based SNP array approach. These promising data when supported by further molecular validation would greatly enhance the current understanding of AML predisposition and diseases progression. Implication of polymorphic variants in AML etiopathogenesis will be presented and discussed.

Identification of Genes Associated with Risk to Aplastic Anemia (AA) Using Array-Based Genotyping.

In this study we tested whether 3104 SNPs in 200 candidate genes were associated with risk to aplastic anemia (AA). Genes were considered potential candidates for their known or suspected roles in DNA repair system, pharmacogenomics and transcriptional regulation in hematopoiesis or putative pathways related to development of AA. Selection of SNPs was performed using dbSNP and HapMap project databases, with emphasis on non-synonymous SNPs or haplotype tagging SNPs. To discover potential SNPs responsible for AA susceptibility, a case-control study using Affymetrix targeted genotyping 3K array was designed. We applied 3K array to analyze the samples from 132 AA patients and 382 healthy controls. Genotyping were processed using GeneChip scanner 3000 TG(Affymetrix) and analyzed with GCOS software(Affymetrix). In total more than 160,000 SNPs were genotyped for this study. Samples with suboptimal call rates were excluded. Statistical testing were carried out using χ2, Cochran-Armitage trend, Fisher's exact, odds ratio, haplotype estimation, LD block definition. Here we report that 19 SNPs in 14 genes are associated with elevated or reduced risk to AA. Three associated genes map to chromosome 11 and 16 respectively. Some of associated genes were transcription factors such as RARB and ZNF233. Among those associated SNPs, one was located in coding region while the rest of SNPs were located in introns of associated genes. In conclusion, we identified SNPs responsible for AA susceptibility by candidate gene-based SNP array approach. These promising data when supported by further molecular validation would greatly enhance the current understanding of AA predisposition and diseases progression. Implication of polymorphic variants in AA etiopathogenesis will be presented and discussed.

DASC standards track IP-based design trends

The common engineering practice of decomposing complex problems into a series of simpler subproblems to arrive at effective solutions is mirrored in the electronics industry by the definition and use of IP blocks. Although such blocks were initially fairly simple, the industry has been moving toward the exchange of highly complex, configurable parts such as microprocessors and digital-signal processors. Hence, there's a need for specific IP standards to manage this increased complexity. Although many aspects of the industry could benefit from standardization, three of them are currently being actively addressed: concise, vendor-neutral descriptions of IP characteristics; metrics for IP quality; and IP encryption for protected information exchange. The new standards that the IEEE Design Automation Standards Committee (DASC) is addressing cover both the technical aspects of IP use and the infrastructure for developing sound business models for IP production and distribution.

Evaluation of sample size effect on the identification of haplotype blocks.

BackgroundGenome-wide maps of linkage disequilibrium (LD) and haplotypes have been created for different populations. Substantial sharing of the boundaries and haplotypes among populations was observed, but haplotype variations have also been reported across populations. Conflicting observations on the extent and distribution of haplotypes require careful examination. The mechanisms that shape haplotypes have not been fully explored, although the effect of sample size has been implicated. We present a close examination of the effect of sample size on haplotype blocks using an original computational simulation.ResultsA region spanning 19.31 Mb on chromosome 20q was genotyped for 1,147 SNPs in 725 Japanese subjects. One region of 445 kb exhibiting a single strong LD value (average |D'|; 0.94) was selected for the analysis of sample size effect on haplotype structure. Three different block definitions (recombination-based, LD-based, and diversity-based) were exploited to create simulations for block identification with θ value from real genotyping data. As a result, it was quite difficult to estimate a haplotype block for data with less than 200 samples. Attainment of a reliable haplotype structure with 50 samples was not possible, although the simulation was repeated 10,000 times.ConclusionThese analyses underscored the difficulties of estimating haplotype blocks. To acquire a reliable result, it would be necessary to increase sample size more than 725 and to repeat the simulation 3,000 times. Even in one genomic region showing a high LD value, the haplotype block might be fragile. We emphasize the importance of applying careful confidence measures when using the estimated haplotype structure in biomedical research.

IHAP – integrated haplotype analysis pipeline for characterizing the haplotype structure of genes

BackgroundThe advent of genotype data from large-scale efforts that catalog the genetic variants of different populations have given rise to new avenues for multifactorial disease association studies. Recent work shows that genotype data from the International HapMap Project have a high degree of transferability to the wider population. This implies that the design of genotyping studies on local populations may be facilitated through inferences drawn from information contained in HapMap populations.ResultsTo facilitate analysis of HapMap data for characterizing the haplotype structure of genes or any chromosomal regions, we have developed an integrated web-based resource, iHAP. In addition to incorporating genotype and haplotype data from the International HapMap Project and gene information from the UCSC Genome Browser Database, iHAP also provides capabilities for inferring haplotype blocks and selecting tag SNPs that are representative of haplotype patterns. These include block partitioning algorithms, block definitions, tag SNP definitions, as well as SNPs to be "force included" as tags. Based on the parameters defined at the input stage, iHAP performs on-the-fly analysis and displays the result graphically as a webpage. To facilitate analysis, intermediate and final result files can be downloaded.ConclusionThe iHAP resource, available at , provides a convenient yet flexible approach for the user community to analyze HapMap data and identify candidate targets for genotyping studies.

A First-Generation Metric Linkage Disequilibrium Map of Bovine Chromosome 6

We constructed a metric linkage disequilibrium (LD) map of bovine chromosome 6 (BTA6) on the basis of data from 220 SNPs genotyped on 433 Australian dairy bulls. This metric LD map has distances in LD units (LDUs) that are analogous to centimorgans in linkage maps. The LD map of BTA6 has a total length of 8.9 LDUs. Within the LD map, regions of high LD (represented as blocks) and regions of low LD (steps) are observed, when plotted against the integrated map in kilobases. At the most stringent block definition, namely a set of loci with zero LDU increase over the span of these markers, BTA6 comprises 40 blocks, accounting for 41% of the chromosome. At a slightly lower stringency of block definition (a set of loci covering a maximum of 0.2 LDUs on the LD map), up to 81% of BTA6 is spanned by 46 blocks and with 13 steps that are likely to reflect recombination hot spots. The mean swept radius (the distance over which LD is likely to be useful for mapping) is 13.3 Mb, confirming extensive LD in Holstein-Friesian dairy cattle, which makes such populations ideal for whole-genome association studies.

The Effect of Single-Nucleotide Polymorphism Marker Selection on Patterns of Haplotype Blocks and Haplotype Frequency Estimates

The definition of haplotype blocks of single-nucleotide polymorphisms (SNPs) has been proposed so that the haplotypes can be used as markers in association studies and to efficiently describe human genetic variation. The International Haplotype Map (HapMap) project to construct a comprehensive catalog of haplotypic variation in humans is underway. However, a number of factors have already been shown to influence the definition of blocks, including the population studied and the sample SNP density. Here, we examine the effect that marker selection has on the definition of blocks and the pattern of haplotypes by using comparable but complementary SNP sets and a number of block definition methods in various genomic regions and populations that were provided by the Encyclopedia of DNA Elements (ENCODE) project. We find that the chosen SNP set has a profound effect on the block-covered sequence and block borders, even at high marker densities. Our results question the very concept of discrete haplotype blocks and the possibility of generalizing block findings from the HapMap project. We comparatively apply the block-free tagging-SNP approach and discuss both the haplotype approach and the tagging-SNP approach as means to efficiently catalog genetic variation.

Analysis of concordance of different haplotype block partitioning algorithms.

BackgroundDifferent classes of haplotype block algorithms exist and the ideal dataset to assess their performance would be to comprehensively re-sequence a large genomic region in a large population. Such data sets are expensive to collect. Alternatively, we performed coalescent simulations to generate haplotypes with a high marker density and compared block partitioning results from diversity based, LD based, and information theoretic algorithms under different values of SNP density and allele frequency.ResultsWe simulated 1000 haplotypes using the standard coalescent for three world populations – European, African American, and East Asian – and applied three classes of block partitioning algorithms – diversity based, LD based, and information theoretic. We assessed algorithm differences in number, size, and coverage of blocks inferred under different conditions of SNP density, allele frequency, and sample size.Each algorithm inferred blocks differing in number, size, and coverage under different density and allele frequency conditions. Different partitions had few if any matching block boundaries. However they still overlapped and a high percentage of total chromosomal region was common to all methods. This percentage was generally higher with a higher density of SNPs and when rarer markers were included.ConclusionA gold standard definition of a haplotype block is difficult to achieve, but collecting haplotypes covered with a high density of SNPs, partitioning them with a variety of block algorithms, and identifying regions common to all methods may be the best way to identify genomic regions that harbor SNP variants that cause disease.

EFFECTIVE ALGORITHMS FOR TAG SNP SELECTION

Single nucleotide polymorphisms (SNPs), due to their abundance and low mutation rate, are very useful genetic markers for genetic association studies. However, the current genotyping technology cannot afford to genotype all common SNPs in all the genes. By making use of linkage disequilibrium, we can reduce the experiment cost by genotyping a subset of SNPs, called Tag SNPs, which have a strong association with the ungenotyped SNPs, while are as independent from each other as possible. The problem of selecting Tag SNPs is NP-complete; when there are large number of SNPs, in order to avoid extremely long computational time, most of the existing Tag SNP selection methods first partition the SNPs into blocks based on certain block definitions, then Tag SNPs are selected in each block by brute-force search. The size of the Tag SNP set obtained in this way may usually be reduced further due to the inter-dependency among blocks. This paper proposes two algorithms, TSSA and TSSD, to tackle the block-independent Tag SNP selection problem. TSSA is based on A* search algorithm, and TSSD is a heuristic algorithm. Experiments show that TSSA can find the optimal solutions for medium-sized problems in reasonable time, while TSSD can handle very large problems and report approximate solutions very close to the optimal ones.

A practical definition of conduction block in IvIg responsive multifocal motor neuropathy

Background: Multifocal motor neuropathy with conduction block (MMN) can be mistaken for motor neurone disease or other lower motor neurone syndromes, but is treatable with intravenous immunoglobulin (IvIg). Formal electrophysiological...

A Hybrid-Agent-Based Approach for Block Break Definition Using Fuzzy Logic

This paper presents a hybrid-agent-based methodology for defining block breaks using fuzzy logic mechanisms for agent preference representation and mediation. The concept of a hybrid agent is defined, and the fuzzy-logic-based mechanisms for defining the preferences of individual agents and then deriving joint preferences are described. Working examples are given for defining blocks and associated breaks in the hold area and engine room of the notional fast sealift ship PD-337. The agents jointly defining the block breaks in these examples are a structure manufacturing planner, a structure assembly planner, and an outfitting planner. Excel spreadsheets are used in these examples to execute the fuzzy-based operations. This methodology has proven to be straightforward, to provide useful results, and to have the potential to improve the efficiency and optimality of block definition. The methodology could be effectively integrated into the detail/production design process and could also be applied to the definition of other planning units, such as outfit units and on-board outfitting zones. Areas of further research include exploring within the hybrid agent and fuzzy-based context (1) the ability to define breaks in all three dimensions simultaneously rather than sequentially where simultaneous three-dimensional optimization is necessary, (2) dynamic break definition where a break location is dependent to some extent on the location of adjacent breaks, (3) the simultaneous consideration of preferences from lifting/weight and planning/work content agents that use block attributes other than location to determine if breaks are satisfactory, and (4) the development of an integrated and user-friendly tool for block break definition for use in the production planning or build strategy development process.

Characterisation of the genomic architecture of human chromosome 17q and evaluation of different methods for haplotype block definition

BackgroundThe selection of markers in association studies can be informed through the use of haplotype blocks. Recent reports have determined the genomic architecture of chromosomal segments through different haplotype block definitions based on linkage disequilibrium (LD) measures or haplotype diversity criteria. The relative applicability of distinct block definitions to association studies, however, remains unclear. We compared different block definitions in 6.1 Mb of chromosome 17q in 189 unrelated healthy individuals. Using 137 single nucleotide polymorphisms (SNPs), at a median spacing of 15.5 kb, we constructed haplotype block maps using published methods and additional methods we have developed. Haplotype tagging SNPs (htSNPs) were identified for each map.ResultsBlocks were found to be shorter and coverage of the region limited with methods based on LD measures, compared to the method based on haplotype diversity. Although the distribution of blocks was highly variable, the number of SNPs that needed to be typed in order to capture the maximum number of haplotypes was consistent.ConclusionFor the marker spacing used in this study, choice of block definition is not important when used as an initial screen of the region to identify htSNPs. However, choice of block definition has consequences for the downstream interpretation of association study results.