bluuebunny/crossref_metadata_2025 huggingface dataset:
Software maintainability assessment based on fuzzy logic technique
Authors: Mittal Harish , Bhatia Pradeep
Published: June 2009

Software maintenance is a process of modifying existing operational software while leaving its primary functions intact. Easily maintainable software saves large costs in industries. Software maintainability assessment is a major issue these days. In order to assess maintainability we consider four major aspects of software i.e., average numbers of live variables, average life span of variables, average cyclomatic complexity and the comment ratio. This paper proposes a fuzzy logic based precise and easy approach to quantify maintainability of software.
Word-length selection for power minimization via nonlinear optimization
Authors: Clarke Jonathan A. , Constantinides George A. , Cheung Peter Y. K.
Published: June 2009

This article describes the first method for minimizing the dynamic power consumption of a Digital Signal Processing (DSP) algorithm implemented on reconfigurable hardware via word-length optimization. Fast models for estimating the power consumption of the arithmetic components and the routing power of these algorithm implementations are used within a constrained nonlinear optimization formulation that solves a relaxed version of word-length optimization. Tight lower and upper bounds on the cost of the integer word-length problem can be obtained using the proposed solution, with typical upper bounds being 2.9% and 5.1% larger than the lower bounds for area and power consumption, respectively. Heuristics can then use the upper bound as a starting point from which to get even closer to the known lower bound. Results show that power consumption can be improved by up to 40% compared to that achieved when using simple word-length selection techniques, and further comparisons are made between the minimization of different cost functions that give insight into the advantages offered by multiple word-length optimization.
Custom topology rotary clock router with tree subnetworks
Authors: Taskin Baris , Demaio Joseph , Farell Owen , Hazeltine Michael , Ketner Ryan
Published: June 2009

Increasing demands on computing power have spurred the development of faster, higher-density Integrated Circuits (ICs), compounding power and complexity concerns in design budgets. The clock distribution network is a significant contributor to such power and complexity concerns. Resonant rotary clocking is a relatively new technology that realizes several benefits over current clocking methods, including power, frequency, and variation tolerance, yet lacks the automation tools to promote increased use. Towards this end, an automated rotary clock routing methodology is presented that generates custom topology rotary ring routes with tree subnetworks. In addition to the benefits of adiabatic clocking, the presented custom topology router permits 38.6% shorter wirelengths on average for register tapping, compared to traditional prescribed skew, binary tree routing.
Theories and algorithms on single-detour routing for untangling twisted bus
Authors: Yan Tan , Wong Martin D. F.
Published: June 2009

Previous works on PCB bus routing assume matched pin ordering on both sides. But in practice, the pin ordering might be mismatched and the nets become twisted. In this article, we propose a preprocessing step to untangle such twisted nets. We also introduce a practical routing style, which we call
single-detour routing
, to simplify the untangling problem. We then present a necessary and sufficient condition for the existence of single-detour routing solutions. Furthermore, we present a dynamic-programming-based algorithm to solve the single-detour untangling problem with consideration of wire capacity between adjacent pins. Our algorithm produces an optimal single-detour routing solution that rematches the pin ordering. By integrating our algorithm into the bus router in a previous length-matching router, we show that many routing problems that cannot be solved previously can now be solved with insignificant increase in runtime.
Practical and low-overhead masking of failures of TCP-based servers
Authors: Zagorodnov Dmitrii , Marzullo Keith , Alvisi Lorenzo , Bressoud Thomas C.
Published: June 2009

This article describes an architecture that allows a replicated service to survive crashes without breaking its TCP connections. Our approach does not require modifications to the TCP protocol, to the operating system on the server, or to any of the software running on the clients. Furthermore, it runs on commodity hardware. We compare two implementations of this architecture (one based on primary/backup replication and another based on message logging) focusing on scalability, failover time, and application transparency. We evaluate three types of services: a file server, a Web server, and a multimedia streaming server. Our experiments suggest that the approach incurs low overhead on throughput, scales well as the number of clients increases, and allows recovery of the service in near-optimal time.
A library for light-weight information-flow security in haskell
Authors: Russo Alejandro , Claessen Koen , Hughes John
Published: June 2009

Protecting confidentiality of data has become increasingly important for computing systems. Information-flow techniques have been developed over the years to achieve that purpose, leading to special-purpose languages that guarantee information-flow security in programs. However, rather than producing a new language from scratch, information-flow security can also be provided as a library. This has been done previously in Haskell using the arrow framework. In this paper, we show that arrows are not necessary to design such libraries and that a less general notion, namely monads, is sufficient to achieve the same goals. We present a monadic library to provide information-flow security for Haskell programs. The library introduces mechanisms to protect confidentiality of data for pure computations, that we then easily, and modularly, extend to include dealing with side-effects. We also present combinators to dynamically enforce different declassification policies when release of information is required in a controlled manner. It is possible to enforce policies related to what, by whom, and when information is released or a combination of them. The well-known concept of monads together with the light-weight characteristic of our approach makes the library suitable to build applications where confidentiality of data is an issue.
Shared subtypes
Authors: Ahn Ki Yung , Sheard Tim
Published: June 2009

A newtype declaration in Haskell introduces a new type renaming an existing type. The two types are viewed by the programmer as semantically different, but share the same runtime representation. When operations on the two semantic views coincide, the run-time cost of conversion between the two types is reduced to zero (in both directions) because of this common representation.

We describe a new language feature called Shared Subtypes (SSubtypes), which generalizes these properties of the newtype declaration. SSubtypes allow programmers to specify subtype rules between types and sharing rules between data constructors. A value of a type T, where T is a subtype of U, can always be cast, at no cost, to value of type U. This free up-casting allows library functions that consume the supertype to be applied without cost to subtypes. Yet any semantic interpretations desired by the programmer can be enforced by the compiler. SSubtype declarations work particularly well with GADTs. GADTs use differing type indexes to make explicit semantic differences, by using a different index for each way of viewing the data. Shared subtypes allow GADTs to share the same runtime representation as a reference type, of which the GADT is a refinement.
Language and program design for functional dependencies
Authors: Jones Mark P. , Diatchki Iavor S.
Published: June 2009

Eight years ago, functional dependencies, a concept from the theory of relational databases, were proposed as a mechanism for avoiding common problems with multiple parameter type classes in Haskell. In this context, functional dependencies give programmers a means to specify the semantics of a type class more precisely, and to obtain more accurate inferred types as a result. As time passed, however, several issues were uncovered - both in the design of a language to support functional dependencies, and in the ways that programmers use them - that led some to search for new, better alternatives.

This paper focusses on two related aspects of design for functional dependencies: (i) the design of language/type system extensions that implement them; and (ii) the design of programs that use them. Our goal is to clarify the issues of what functional dependencies are, how they should be used, and how the problems encountered with initial proposals and implementations can be addressed.
The Advent of Near-Atomic Resolution in Single-Particle Electron Microscopy
Authors: Cheng Yifan , Walz Thomas
Published: June 2009

Single-particle electron microscopy (EM) can provide structural information for a large variety of biological molecules, ranging from small proteins to large macromolecular assemblies, without the need to produce crystals. The year 2008 has become a landmark year for single-particle EM as for the first time density maps have been produced at a resolution that made it possible to trace protein backbones or even to build atomic models. In this review, we highlight some of the recent successes achieved by single-particle EM and describe the individual steps involved in producing a density map by this technique. We also discuss some of the remaining challenges and areas, in which further advances would have a great impact on the results that can be achieved by single-particle EM.
Mechanism of Mo-Dependent Nitrogenase
Authors: Seefeldt Lance C. , Hoffman Brian M. , Dean Dennis R.
Published: June 2009

Nitrogen-fixing bacteria catalyze the reduction of dinitrogen (N2) to two ammonia molecules (NH3), the major contribution of fixed nitrogen to the biogeochemical nitrogen cycle. The most widely studied nitrogenase is the molybdenum (Mo)-dependent enzyme. The reduction of N2 by this enzyme involves the transient interaction of two component proteins, designated the iron (Fe) protein and the MoFe protein, and minimally requires 16 magnesium ATP (MgATP), eight protons, and eight electrons. The current state of knowledge on how these proteins and small molecules together effect the reduction of N2 to ammonia is reviewed. Included is a summary of the roles of the Fe protein and MgATP hydrolysis, information on the roles of the two metal clusters contained in the MoFe protein in catalysis, insights gained from recent success in trapping substrates and inhibitors at the active-site metal cluster FeMo cofactor, and finally, considerations of the mechanism of N2 reduction catalyzed by nitrogenase.
Biosynthesis of Phosphonic and Phosphinic Acid Natural Products
Authors: Metcalf William W. , van der Donk Wilfred A.
Published: June 2009

Natural products containing carbon-phosphorus bonds (phosphonic and phosphinic acids) have found widespread use in medicine and agriculture. Recent years have seen a renewed interest in the biochemistry and biology of these compounds with the cloning of the biosynthetic gene clusters for several family members. This review discusses the commonalities and differences in the molecular logic that lie behind the biosynthesis of these compounds. The current knowledge regarding the metabolic pathways and enzymes involved in the production of a number of natural products, including the approved antibiotic fosfomycin, the widely used herbicide phosphinothricin (PT), and the clinical candidate for treatment of malaria FR-900098, is presented. Many of the enzymes involved in the biosynthesis of these compounds catalyze chemically and biologically unprecedented transformations, and a wealth of new biochemistry has been revealed through their study. These investigations have also suggested new strategies for natural product discovery.
AMPK inhibits myoblast differentiation through a PGC-1α-dependent mechanism
Authors: Williamson David L. , Butler David C. , Alway Stephen E.
Published: June 2009

Elevated phosphorylation of AMP-activated protein kinase (AMPK) has been shown to inhibit skeletal muscle growth in both culture and animal models, but its role in differentiation of muscle cells is less clear. p21 is known to have an important role in differentiation, but AMPK's role regulating p21 in differentiation in muscle cultures is unknown. Therefore, the purpose of this study was to determine the role of p21 in differentiation of skeletal muscle cells under conditions of elevated AMPK phosphorylation. Treating C2C12 myoblast cultures with 1 mM 5-aminoimidazole-4-carboxamide 1-β-d-ribonucleoside (AICAR) for up to 24 h induced AMPK phosphorylation. Activation of AMPK reduced p21 protein and mRNA expression, which was associated with reduced G1/S cell cycle transition and p21 promoter activity. AICAR-treated myoblasts undergoing differentiation also had reduced p21 protein expression, reduced myotube formation, and myosin accumulation. When myotube cultures were treated with AICAR for 24 h, p21, myosin protein expression, and MyoD were significantly reduced. Myotube atrophy was also apparent compared with control conditions. Addition of compound C, an AMPK inhibitor, attenuated AICAR's negative effects on the myotube cultures. The nuclear expression of p21 protein appeared to be more affected by AICAR-treated myotubes than the cytosolic portion of p21 protein, which was attenuated with compound C treatment. Further analysis revealed that AICAR treatment increased PGC-1α and decreased FOXO3A protein expression, which was reversed with compound C cotreatment. Knockdown of PGC-1α with shRNA corroborated the compound C data, preserving nuclear FOXO3A and p21 protein expression. These data demonstrate that AICAR-induced AMPK phosphorylation inhibits cell cycle transition, reducing differentiation of myoblasts into myotubes, through PGC-1α-FOXO3A-p21.
UAVs Dynamic Mission Management in Adversarial Environments
Authors: Faied Mariam , Assanein Ihemed , Girard Anouck
Published: June 2009

We address a dynamic configuration strategy for teams of Unmanned Air Vehicles (UAVs). A team is a collection of UAVs which may evolve through different organizations, called configurations. The team configuration may change with time to adapt to environmental changes, uncertainty, and adversarial actions. Uncertainty comes from the stochastic nature of the environment and from incomplete knowledge of adversary behaviors. To each configuration, there corresponds a set of different properties for the UAVs in the team. The design for the configuration control problem involves a distributed hierarchical control architecture where the properties of the system can be formally analyzed. We do this in the framework of dynamic networks of hybrid automata. We present results from simulation to demonstrate different scenarios for adversarial response.
Modeling Nonlinear Dynamics and Chaos: A Review
Authors: Aguirre Luis A. , Letellier Christophe
Published: June 2009

This paper reviews the major developments of modeling techniques applied
to nonlinear dynamics and chaos. Model representations, parameter
estimation techniques, data requirements, and model validation are some of
the key topics that are covered in this paper, which surveys slightly over two
decades since the pioneering papers on the subject appeared in the literature.
Periodic and Solitary Wave Solutions to the Fornberg‐Whitham Equation
Authors: Zhou Jiangbo , Tian Lixin
Published: June 2009

New travelling wave solutions to the Fornberg‐Whitham equation ut − uxxt + ux + uux = uuxxx + 3uxuxx are investigated. They are characterized by two parameters. The expresssions for the
periodic and solitary wave solutions are obtained.
ZPC Matrices and Zero Cycles
Authors: Arav Marina , Hall Frank , Li Zhongshan , Rao Bhaskara
Published: June 2009

Let H be an m×n real matrix and let Zi be the set of column indices of the zero entries of row i of H. Then the conditions |Zk∩(∪i=1k−1Zi)|≤1 for all k  (2≤k≤m) are called the (row) Zero Position Conditions (ZPCs). If H satisfies the ZPC, then H is said to be a (row) ZPC matrix. If HT satisfies the ZPC, then H is said to be a column ZPC matrix. The real matrix H is said to have a zero cycle if H has a sequence of at least four zero entries of the form hi1j1,hi1j2,hi2j2,hi2j3,…,hikjk,hikj1 in which the consecutive entries alternatively share the same row or column index (but not both), and the last entry has one common index with the first entry. Several connections between the ZPC and the nonexistence of zero cycles are established. In particular, it is proved that a matrix H has no zero cycle if and only if there are permutation matrices P and Q such that
PHQ is a row ZPC matrix and a column ZPC matrix.
Synthesis and Evaluation of Novel Organogermanium Sesquioxides As Antitumor Agents
Authors: Zhang Chun Li , Li Tai Hua , Niu Shuang Huan , Wang Rong Fu , Fu Zhan Li , Guo Feng Qin , Yang Ming
Published: June 2009

Five new organogermanium sesquioxides have been synthesized and characterized by elemental analysis and IR spectra. All the compounds were tested for antitumor activities against KB, HCT, and Bel cells in vitro. Compound 5 (γ‐thiocarbamido propyl germanium sesquioxide) showed excellent antitumor activity, and its inhibition yield to KB, HCT, and Bel cells was 92.9%, 84.9%, and 70.9%, respectively. A rapid method was described for the labeling compound 5 with  99mTc, and the optimum labeling conditions were investigated. The labeling yield is above 90% in pH 7.0, 20∘C, reaction time greater than 10 minutes, 1 mg of compound 5, and 0.075∼0.1 mg of SnCl2. The biodistribution of  99mTc labeled compound 5 in nude mice bearing human colonic xenografts was studied. The result showed that the tumor uptakes were 0.73, 0.97, 0.87, and 0.62 ID%/g at 1‐hour, 3‐hour, 6‐hour, and 20‐hour postinjection, respectively. T/NT (the uptake ratio for per gram of tumor over normal tissues) was 18.3 for tumor versus brain and 5.81 for tumor versus muscle at 20‐hour postinjection. The tumor clearance was slow. The results showed that compound 5 may be developed to be a suitable cancer therapeutic agent.
Necessary Conditions for a Class of Optimal Control Problems on Time Scales
Authors: Zhan Zaidong , Wei W.
Published: June 2009

Based on the Gateaux differential on time scales, we investigate and establish necessary conditions for Lagrange optimal control problems on time scales. Moreover, we present an economic model to demonstrate the effectiveness of our results.
Inhibition of Matrix Metalloproteinase-9 with Doxycycline Reduces Pancreatitis-Associated Lung Injury
Authors: Sochor Markus , Richter Sabine , Schmidt Anja , Hempel Silke , Hopt Ulrich T. , Keck Tobias
Published: June 2009

Background/Aims: Severe lung injury, responsible for up to 15% of mortality in acute necrotizing pancreatitis patients, is promoted by neutrophil (PMN) migration into the lung. We have previously demonstrated that pulmonary injury in acute pancreatitis is mediated by PMN-derived matrix metalloproteinase-9 (MMP-9). This study was conducted to evaluate the ability of the broad-spectrum MMP inhibitor doxycycline to prevent secondary pulmonary injury in acute pancreatitis. Methods: Eighteen rats were randomized into three groups: severe pancreatitis (SAP), severe pancreatitis + doxycycline (SAP+Dox) (30 mg/kg body mass) or control. Acute pancreatitis was induced by intraductal glycodesoxycholic acid and i.v. stimulation with cerulein. Lung sections were histologically graded for edema, microthrombi, atelectasis and hemorrhage. Active MMP-9 in lung tissue was measured with fluorescent assay (ELISA). Naphtol-AS-D-chloroacetate esterase staining was used to determine pulmonary PMN infiltration. The inhibitory effect of doxycycline on MMP-9-induced transmigration was confirmed in a Matrigel transmigration assay. Results: Addition of doxycycline significantly reduced TNF-α-induced PMN transmigration across Matrigel membrane (12.6 ± 2.6 vs. 20.1 ± 3.9 PMNs; p < 0.05). SAP+Dox showed decreased concentration of active MMP-9 in lung tissue (37.89 ± 1.75 vs. 46.29 ± 3.68 ng/ml; p < 0.05) and as a result decreased pulmonary infiltration of PMNs (21.2 ± 5.1 vs. 32.5 ± 6.8; p < 0.05). Histological evaluation revealed decreased pulmonary edema (1.83 ± 0.41 vs. 2.33 ± 0.51, p < 0.05), atelectasis (1.67 ± 0.52 vs. 2.33 ± 0.52; p < 0.05) and pulmonary hemorrhage (2.5 ± 0.55 vs. 1.83 ± 0.41; p < 0.05) in SAP+Dox vs. SAP. These findings were paralleled by reduced pulmonary expression of active MMP-9. Conclusions: Inhibition of MMP-9 activity with doxycycline reduced pancreatitis-associated lung injury and expression of MMP-9 in pulmonary tissue. Doxycycline reduced PMN migration in vitro and in vivo and therefore might represent a novel strategy for the prevention of secondary pulmonary complications in acute pancreatitis.
Plasma Ghrelin Levels and Their Relationship with Gastric Emptying in Patients with Dysmotility-Like Functional Dyspepsia
Authors: Lee K.J. , Cha D.Y. , Cheon S.J. , Yeo M. , Cho S.W.
Published: June 2009

Background/Aims: Ghrelin affects gastric motility. However, little is known about the role of ghrelin in the pathophysiology of functional dyspepsia (FD). We investigated plasma ghrelin levels and their relationship with gastric emptying time in dysmotility-like FD patients. Methods: 42 patients with dysmotility-like FD and 14 healthy volunteers were enrolled in the study. Gastric half-emptying time was measured using a radiolabeled meal. Plasma total ghrelin levels before and after the meal were determined using a radioimmunoassay kit. Results: Preprandial ghrelin levels were significantly lower in FD patients than in controls. Postprandial ghrelin levels were similar between the two groups. Abnormally low preprandial ghrelin levels were observed in 7 out of 42 patients, in whom significant postprandial decrease of ghrelin levels was absent. Delayed gastric emptying was observed in 5 out of 7 patients with abnormally low ghrelin levels. Pre- or postprandial ghrelin levels were not significantly correlated with gastric half-emptying time, both in the patient group and in the control group. Conclusions: Abnormally low preprandial ghrelin levels and absence of significant postprandial decrease of ghrelin levels are present in a subset of dysmotility-like FD patients. Further investigation on the pathogenetic implication of these alterations in FD is required.
Determinant Factors of Renal Failure after Coronary Artery Bypass Grafting with On-Pump Technique
Authors: Ahmadi Hossein , Karimi Abbasali , Davoodi Saeed , Movahedi Namvar , Marzban Mehrab , Abbasi Kyomars , Salehi Omran Abbas , Shirzad Mahmud , Abbasi Seyed Hesameddin , Tazik Mokhtar
Published: June 2009

Objective: The aim of the present study was to investigate the determinant factors of acute renal failure (ARF) after isolated on-pump coronary artery bypass grafting (CABG). Subjects and Methods: This was a retrospective study of 13,315 adult patients who underwent isolated CABG with cardiopulmonary bypass (CPB) in Tehran Heart Center from May 2002 to May 2007. The exclusion criteria were age <18, concomitant cardiac and/or noncardiac surgical operations, history of renal failure before surgery, and chronic renal failure requiring dialysis. Preoperative and operative variables were measured, and a multivariate logistic regression model was constructed to identify the independent risk factors for developing renal failure after on-pump CABG. Results: Of the 13,315 patients, 3,347 (25.4%) and 90,883 (74.6%) were females and males, respectively, with a mean age of 58.63 ± 9.48 years. ARF was detected in 85 (0.6%) of the patients with isolated on-pump CABG. The mean age of the patients was 58.63 ± 9.48 years, and 25.5% of them were female. The multivariate logistic regression analysis identified age (OR = 1.035; p = 0.002), female gender (OR = 1.622; p = 0.037), history of peripheral vascular disease (PVD) (OR = 2.579; p = 0.042), diabetes mellitus (OR = 1.918; p < 0.001), emergent and urgent surgery (OR = 1.744 and OR = 7.901, respectively; p = 0.003), CPB time >70 min (OR = 1.944; p = 0.007), and intra-aortic balloon pump (IABP) insertion (OR = 10.181; p < 0.001) as the independent risk factors for ARF. Conclusion: The data showed that age, female gender, positive history of diabetes and PVD, urgent and emergent surgery, CPB time >70 min, and need for IABP were the independent determinant factors of ARF after on-pump CABG.
Perceived Health Status of Women with Overt and Subclinical Hypothyroidism
Authors: Vigário Patrícia , Teixeira Patrícia , Reuters Vaneska , Almeida Cloyra , Maia Maicon , Silva Marina , Vaisman Mário
Published: June 2009

Objective: The objective of this study was to investigate the health status of women with overt and subclinical hypothyroidism and relate it to the presence of clinical signs and symptoms of the disease. Subjects and Methods: A cross-sectional study was conducted on 232 women divided into 3 groups: overt hypothyroidism (n = 14); subclinical hypothyroidism (n = 152), and controls (n = 66). Health status was evaluated by the questionnaire SF-36, and the clinical signs and symptoms of hypothyroidism were assessed with the Billewicz scale modified by Zulewski. The Kruskal-Wallis test followed by the Mann-Whitney U test with Bonferroni correction was applied to compare continuous variables between the groups. To assess the relationship between SF-36 domains and the clinical score, as well as SF-36 domains and serum thyroid-stimulating hormone levels, the Spearman correlation coefficient was calculated. Results: Patients with overt hypothyroidism presented systematically lower scores in all SF-36 domains (p < 0.05), both in relation to subclinical hypothyroidism patients and controls. This indicates a great dissatisfaction with health status in this group. Patients with subclinical hypothyroidism presented statistically lower scores in relation to controls with the exception of the role-emotional and bodily pain domains, where although they were not statistically significant, scores were clinically different. Highly negative correlations between SF-36 domains and the clinical score were observed in overt hypothyroidism (physical function r = –0.80, p < 0.01; bodily pain r = –0.74, p < 0.01). Conclusion: Overt hypothyroidism seemed to be associated with worse perception of health status, negatively associated with clinical score.
Accuracy of 64-Multidetector-Row Computed Tomography in the Diagnosis of Coronary Artery Disease
Authors: Sheikh Mehraj , Ben-Nakhi AbdelMohsen , Shukkur A. Mohemad , Sinan Tariq , Al-Rashdan Ibrahim
Published: June 2009

Objectives: The aim of this prospective study was to assess the accuracy of 64-multidetector-row computed tomography coronary angiography (CTA) in the diagnosis of coronary artery disease (CAD). Patients and Methods: Ninety-two patients suspected of having CAD underwent CTA using a 64-slice CT scanner before a scheduled, conventional coronary angiogram (CCA). Blinded assessment of CTA to detect CAD was performed. The accuracy of CTA in detecting significant stenoses (≥50%) was compared to CCA. Data analysis was performed on 73 patients because the scans were nondiagnostic in 5 patients and 14 refused to undergo coronary angiography. Results: The CTAs of 21 of these 73 patients were considered as normal; 19 were confirmed on CCA. For the remaining 52 diagnosed as abnormal, 51 were confirmed on CCA. For patient-based analysis, CTA had a sensitivity of 95%, a specificity of 96%, a positive predictive value of 98% and a negative predictive value of 90%. For the whole vessel, the sensitivity of CTA was 60–100%, for all vessels and the specificity was 82–100%. Pooled sensitivity was 92% and pooled specificity was 98%. For the segments, the sensitivity of CTA was 64% or above for all vessels except for the distal left anterior descending artery (40%), mid circumflex artery (50%) and posterior descending artery (60%); the pooled sensitivity was 79%. The specificity for the segments was 82–100% for all vessels and pooled specificity was 94%. Conclusion: The sensitivity and specificity for patient-based analysis and for the main coronary vessels were high whereas for the segments, the sensitivity was moderately good, but the specificity was high, confirming that a negative CTA is useful to rule out significant CAD. A coordinated classification system between radiologists and cardiologists is required to eliminate errors in segment classification.
Phenotypic Expression in the First Case of Complete Trisomy 12: Combination of Prenatal Ultrasound and Necropsic Examination
Authors: Machado Ana Paula , Ramalho Carla , Loureiro Teresa , Cunha Manuela , Dória Sofia , Carvalho Filipa , Oliveira João Paulo , Brandão Otília , Matias Alexandra
Published: June 2009

The authors report the first case of a complete trisomy 12 detected antenatally at 16 weeks of gestation. The ultrasonographic features (craniofacial abnormalities) correlated well with postmortem findings. The absence of the hypophysis gland, olfactory pathways and both adrenal glands, as well as developmental anomalies of the central nervous system, were additional findings at autopsy. The recognition of complete trisomy 12 phenotype can be helpful in the pre- and postnatal diagnosis of future similar cases and parental counseling.
The Management of Hydrocephalus in Children with Posterior Fossa Tumours: The Role of Pre-Resectional Endoscopic Third Ventriculostomy
Authors: Bhatia Robin , Tahir Mohammed , Chandler Christopher L.
Published: June 2009

Aims: The purpose of this retrospective case series was to determine the incidence of complications and outcomes associated with a primary management policy of endoscopic third ventriculostomy (ETV) prior to posterior fossa tumour resection in a single paediatric neurosurgical unit. Methods: Between July 1999 and August 2007, 59 children with posterior fossa tumours were surgically managed. Based on presenting neurology, imaging criteria and cerebrospinal fluid (CSF) pressure during ventriculostomy, patients were categorised into no (n = 16), mild (6), moderate (22) or severe (15) hydrocephalus on admission. Results: Thirty-seven (63%) patients underwent ETV within (mean) 1.5 days of admission, and of those, 32 (87.1%) exhibited significant improvement in presenting symptomology immediately after ETV. Complications arising after ETV included CSF infection/meningitis (n = 2) and bleeding (n = 1). ETV failed in 5/37 patients over the follow-up period. There was a significant association between increasing severity of hydrocephalus before ETV and increased number of complications (p = 0.03). Conclusions: The use of pre-resectional ETV at this institution is an effective and safe procedure with a high success rate at up to 7.5 years of follow-up. We believe that all paediatric neurosurgical institutions should review their practice regarding hydrocephalus associated with posterior fossa tumours in the light of the controversy surrounding perioperative CSF diversion.
Präoperative Gerinnungsdiagnostik – Eine “Conditio sine qua non”?
Authors: Marte W.
Published: June 2009

Die präoperative Gerinnungsdiagnostik stellt trotz vorhandener Richtlinien einen nicht unumstrittenen Bestandteil des laborchemischen Routinescreenings dar, zumal eine Vielzahl von Studien den Nutzen einer Durchführung unter bestimmten patientenspezifischen Voraussetzungen, im Hinblick auf ein verbessertes perioperatives Outcome, nicht bestätigten. Die Durchführung eines präoperativen Gerinnungsscreenings sollte bei Erwachsenen von den Faktoren Anamnese, ASA-Klassifikation, Art der Operation und Alter abhängig gemacht werden. Bei Kindern ist eine «step-by-step»-Screeningmethode aufgrund einer oftmals nicht vorhandenen Blutungsanamnese angezeigt.
Perioperatives Gerinnungslabor
Authors: Ramschak H.
Published: June 2009

Obwohl derzeit immer mehr Autoren einen präoperativen Blutgerinnungsstatus nicht mehr als obligat erforderlich ansehen, erscheint dieser zumindest bei unklarer hämostaseologischer Anamnese und/oder Klinik nicht zuletzt aus forensischen Gründen indiziert. Zwingend erforderlich erscheint allerdings das Erheben einer spezifischen Anamnese, die sowohl den Patienten als auch dessen Blutsverwandte erfassen sollte. Eine klinische Untersuchung kann gute Hinweise auf das Vorliegen eines angeborenen oder erworbenen Defekts der Blutstillung (Koagulopathie und/oder Thrombopenie/-pathie) geben. Präoperativ gilt heute als laborspezifische Minimalerfordernis die Bestimmung der Prothrombinzeit nach Quick, der aktivierten partiellen Thromboplastinzeit, des Fibrinogens und der Thrombozytenzahl. Eine Erweiterung der Diagnostik ist indiziert bei unklaren anamnestischen Angaben oder bei pathologischen Befunden im Rahmen der klinischen Untersuchung. Intra- oder postoperativ kann je nach klinischer Situation ebenfalls eine weiterführende Diagnostik indiziert sein, wobei immer ein möglichst rationales und rationelles Vorgehen anzustreben ist.
Hypothermie und Gerinnung
Authors: Sitzwohl C. , Dumitrescu R.-V. , Lorber C. , Illievich U.M.
Published: June 2009

Hypothermie wird im allgemeinen mit perioperativen Gerinnungsstörungen in Zusammenhang gebracht. In vitro und tier-experimentelle Arbeiten zeigen, daß Blutgerinnungszeiten, vor allem wenn sie temperaturkorrigiert, d.h. bei der aktuellen Temperatur gemessen werden, bei Hypothermie verlängert sind. Dabei werden jedoch temperaturkorrigierte Daten mit nicht temperaturkorrigierten Normalwerten verglichen und viele komplexe Interaktionen des Gerinnungssystems außer Acht gelassen. Am Menschen durchgeführte Untersuchungen wurden im allgemeinen in Situationen mit aktiviertem Gerinnungssystem [Extrakorporale Zirkulation (EKZ), Trauma etc.] durchgeführt und lassen daher keinen Rückschluß auf die Auswirkungen der Hypothermie per se auf ein im Gleichgewicht befindliches Hämostasesystem zu. Perioperativ auftretende Blutungen sollten bei hypothermen Patienten mit ausreichenden Gerinnungsfaktoren durch Erwärmung und nicht mittels ungezielter Gerinnungsfaktorengabe therapiert werden.
Thromboembolieprophylaxe und rückenmarksnahe Regionalanästhesie
Authors: Neuray M.
Published: June 2009

Rückenmarksnahe Hämatome sind sehr seltene Komplikationen einer Regionalanästhesie. Sie können auch spontan auftreten. Ob ihre Inzidenz durch eine perioperative Thromboembolieprophylaxe mit Heparin oder niedermolekularen Heparinen erhöht wird, wird anhand dieser Literaturübersicht überprüft. Dies kann derzeit nicht mit letzter Sicherheit ausgeschlossen werden. Die veröffentlichten Studien scheitern an letztlich zu geringen Fallzahlen und lassen oft wesentliche Detailangaben vermissen. Dennoch sind rückenmarksnahe Regionalanästhesien auch unter medikamentöser Thromboseprophylaxe durchaus möglich. Hinsichtlich des Vorgehens unter den verschiedenen Pharmaka haben sich heute jeweils besondere Vorsichtsmaßahmen etabliert. Am wenigsten abgesichert ist derzeit eine präoperative Dauertherapie mit niedermolekularen Heparinen und eine Einnahme von Acetylsalicylsäure kurz vor der Operation. In alien Fallen ist vom Anästhesisten eine erhöhte Aufmerksamkeit und ein auf den Patienten bezogenes, individuelles Vorgehen gefordert. Besonders gilt es, weitere Risikofaktoren für ein rückenmarksnahes Hämatom zu vermeiden und das Punktionstrauma zu minimieren.
Autologe Blutkomponentenspende mit dem Programm PES2 des Zellseparators MCS 3p
Authors: Pruß A. , Petrow R. , Siebert G. , Radtke H. , Koscielny J. , Kiesewetter H.
Published: June 2009

Hintergrund: Gegenwärtig geht der Trend auf dem Gebiet der autologen Blutspende in die Richtung qualitätsverbessernder Maßnahmen. Seit Anfang der neunziger Jahre wurde in mehreren transfusionsmedizinischen Einrichtungen die Möglichkeit der maschinellen Eigenblutspende geprüft. Die vorliegende Arbeit überprüft die Eignung des Zellseparationsprogramms PES2 (MCS3p, Fa. Haemonetics) für die Eigenblutspende. Material und Methodik: PES2-Programm, Zellseparator MCS3p, Gewinnung von einem Erythrozytenkonzentrat (bca. resuspendiert in SAG-M) und einem Frischplasma, Datenerhebung an 314 Eigenblutspenden, Erfassung unerwünschter Wirkungen, Darstellung von Entnahmeparametern, Charakterisierung der Blutderivate am Tag 0, 14 und 35. Ergebnisse: Die klinische Verträglichkeit des Protokolls ist als sehr gut einzuschätzen. Die Nebenwirkungsrate betrug 2.28%. Die Werte des Hämoglobins (11,57 mmol/l) und des Hämatokrits (61,9%) am Tag 0 sind mit den Parametern konventionell hergestellter Konserven vergleichbar. Die Leukozytenkontamination der Erythrozytenkonzentrate am Tag 0 liegt im oberen Grenzbereich (1,24×109/Transfusionseinheit). Der Thrombozytenwert am Tag 0 von 32.92 Gpt/1 entspricht einer Konzentration von 9,21 × 109/Transfusionseinheit. Die Hämolyserate am Ende der Lagerungszeit betrug 0,51%/Transfusionseinheit. Schlußfolgerung: Die sehr gute Verträglichkeit der Separation, die leichte Bedienbarkeit sowie die gute Konservenqualität empfehlen das Programm PES2 für einen weiteren Einsatz in transfusionsmedizinischen Einrichtungen und Krankenhäusern, die ein eigenes Eigenblutprogramm aufbauen wollen.
Volumensubstitution in der perioperativen Phase unter besonderer Berücksichtigung der Kardiochirurgie
Authors: Boldt J.
Published: June 2009

Einem suffizienten Volumenersatz kommt beim kritischkranken Intensivpatienten und besonders auch im Rahmen herzchirurgischer Eingriffe besondere Bedeutung zu. Neben einem kristalloiden Volumenersatz stehen eine Reihe verschiedener kolloidaler Lösungen wie Albumin, Dextran, Gelatinepräparate und Hydroxyäthylstärke (HES)-Lösungen in unterschiedlicher Konzentration und Zusammensetzung zur Verfügung. Die Wahl des «idealen Volumenersatzes» wird weiterhin kontrovers diskutiert. Von besonderer Bedeutung sind bei Anwendung der extrakorporalen Zirkulation (EKZ) mögliche Veränderungen im Bereich des Interstitiums, der Gerinnung und der inflammatorischen Antwort. Veränderungen der Mikrozirkulation mit konsekutiver Hypoxie und Anoxie der zu versorgenden Gewebeteile scheinen von besonderer Bedeutung zu sein. Bedingt durch die Aktivierung dieser Mediatorsysteme kommt es zu einer zunehmenden Permeabilitätsstörung im Sinne eines Membranlecks (‘capillary leakage’) mit konsekutiver Manifestierung einer Organinsuffizienz. Die «ideale» Volumentherapie sollte nicht allein zu einer hämodynamischen Stabilisierung führen, sondern auch positiven Einfluß auf die Mikrozirkulation haben. Kolloidale Lösungen führen rascher zu einer Stabilisierung des Blutvolumens. Selbst große Mengen an Kristalloiden reichen oft nicht aus, das zirkulierende Blutvolumen zu stabilisieren. Zur Kontroverse «kristalloider versus kolloidaler Volumenersatz» ist in letzter Zeit noch die Kontroverse «kolloidaler versus kolloidaler Volumenersatz» dazugekommen. Für den Einsatz von Humanalbumin gibt es nur wenige schlüssige Argumente, insbesondere erscheint die Gabe5%iger Humanalbumin-Lösungen kaum sinnvoll. Hydroxyäthylstärke stellt eine sinnvolle Alternative dar. Neuere HES-Präparationen führen zu einer suffizienten Verbesserung der Makro- und Mikrozirkulation ohiie negative Effekte auf Gerinnung und Immunologie.
Oxygen-Carrying Blood Substitutes
Authors: Waschke K.F. , Quintet M. , Kerger H. , Lenz C.
Published: June 2009

Transfusion of human blood components still has major drawbacks, such as transfusion-transmitted diseases, requirements for blood type analysis and cross-match testing, availability and supply, storage and preservation time. The rapid progress in science and technology has advanced to a critical stage where safe and effective alternatives to the transfusion of red blood cells emerge. Although some toxicity issues remain, substantial improvements in the area of artificial oxygen carriers have been made in the past years. To date hemoglobin- and perfluorocarbon-based oxygen carriers are under clinical investigation. In addition to their use as red blood cell substitutes other clinical applications of artificial oxygen carriers should be considered. Due to their physiological properties (especially acellular oxygen transport) artificial oxygen-carrying solutions can be used to provide oxygen to ischemic tissues which cannot be reached by cellular blood components. Longer preservation times of organs awaiting transplantation have been described after perfusion with artificial oxygen carriers as well as an increase in tumor susceptibility to chemo- and radiotherapy. Therefore, artificial oxygen carriers are not only confined to their use as red blood cell substitutes, but will find a wide and divergent spectrum of interdisciplinary applications. Since blood transfusion is a big business and enormous amounts of capital have been invested in the search of artificial oxygen carriers, it can be assumed that substitutes of red blood cells will be available during the next years. However, since there is no anticipated substitute for all fractions of human blood, there will be an ongoing requirement for human blood components, such as fresh frozen plasma, platelets, and others.
Coagulation Disorders Induced by L-Asparaginase: Correction with and without Fresh-Frozen Plasma
Authors: Glasmacher A. , Kleinschmidt R. , Unkrig C. , Mezger J. , Scharf R.E.
Published: June 2009

Objective: L-asparaginase is a potent inhibitor of protein synthesis that may cause deficiencies in several haemostatic proteins, including fibrinogen and antithrombin III, with consequent haemorrhagic or thromboembolic complications. Fresh-frozen plasma has been used to prevent these complications. Its administration has, however, several disadvantages including hypervolaemia and risk of viral transmission. The aim of the present study was to evaluate the efficacy and the expense of a more specific substitution therapy using heat-inactivated concentrates of fibrinogen and antithrombin III and low-dose heparin as compared to therapy with fresh-frozen plasma. Design: Observational study. Setting: Leukaemia unit of a university hospital. Patients: Thirteen patients with de novo acute lymphoblastic leukaemia received 5,000 U/m2 L-asparaginase for 14 days. Interventions: Eight patients were substituted with fibrinogen and antithrombin III (group A) and 5 patients with fresh-frozen plasma and antithrombin III (group B). Results: In all 13 patients median plasma levels of fibrinogen and antithrombin III decreased within 7 days after initiation of L-asparaginase treatment to 0.087 g/l (range 0.055-0.303 g/l) and 62% (43-69%), respectively. Appropriate substitution by both regimens prevented a further decrease of fibrinogen and antithrombin III. Group A received a median total of 13,350 U antithrombin III (5,000-23,800 U) and 4,000 mg of fibrinogen (2,500-15,000 mg), group B 3,420 ml (1,140-6.270 ml) of fresh-frozen plasma and 8,500 U (2,500-15,000 U) antithrombin III (p = 0.107 for the administration of antithrombin III). Drug costs did not differ significantly between group A: 5,083 DM (3,060-10,472 DM) and group B: 4,668 DM (2,184-7,035 DM) (p = 0.380). Conclusion: The use of fibrinogen and antithrombin III can replace fresh-frozen plasma during L-asparaginase therapy without increasing the cost of treatment.
Comparison of the Initial Distribution Volume of Glucose and Sucrose in Volume-Challenged Dogs
Authors: Takamura K. , Iwakawa T. , Sakai I. , Muraoka M. , Ishihara H. , Matsuki A.
Published: June 2009

Objective: Sucrose has been used as an estimate of the extracellular fluid (ECF) volume. This study was designed to examine the hypothesis that the initial distribution volume of glucose (IDVG) correlates with the initial distribution volume of sucrose (IDVS) following volume challenges. Design: Prospective study for comparison of two methods. Setting: Animal laboratory of the University of Hirosaki School of Medicine. Materials and Methods: Ten mongrel dogs of either sex, weighing 8.5-14.0 kg, were the subject of the study. Dogs were anesthetized with pentobarbital and paralyzed with pancuronium. The volume challenge was conducted with 3% dextran in lactated Ringer’s solution 30 ml · kg–1 over 30 min in 10 dogs. Thereafter, the same amount of the fluid was further administered in 8 of these 10 dogs. Before and after each volume challenge, glucose (100 mg·kg–1) and sucrose (100 mg·kg–1) were infused simultaneously over 30 s. The two estimates were calculated using a one-compartment model from repeated measurements of increased plasma glucose and sucrose during postinfusion. Results: A linear correlation was obtained between the two estimates (r = 0.89, n = 28, p< 0.0001). All dogs consistently showed that the IDVG individually followed the IDVS during changes in the latter. Conclusions: Results demonstrated that the IDVG correlated with the IDVS before and after volume changes and support the hypothesis that the IDVG is useful for evaluating the ECF volume status of highly perfused tissues.
Äquivalenzen zwischen Normen und Regelwerken (Teil I)
Authors: Markowetz D. , Grunenberg R. , Krüger J.
Published: June 2009

Teil I reproduziert und erweitert zwei Beiträge, die auf dem 28. Kongreβ der Deutschen Gesellschaft für Transfusionsmedizin und Immunhämatologie (DGTI) in Wien (17.-20.9.1995) präsentiert wurden. Die Autoren diskutieren methodische Er-gebnisse, die sie beim Ausbau des bereits seit vielen Jahren vorhandenen Qualitätsmanagement-Systems (QM-Systems) erzielten. Im Mittelpunkt stehen die qualitätsrelevanten Prozesse in alien Bereichen und auf alien Ebenen des Instituts für Transfusionsmedizin der Universität zu Köln. Diese Prozesse werden auf die nach den Bedürfnissen des Instituts hin maβgeschneiderte Norm DIN EN ISO 9001 abgebildet. Aus den Ergebnissen dieser Abbildung wird eine Strategic zum weite-ren Ausbau des aktuellen QM-Systems abgeleitet. In der Diskussion werden auch die Realisierungschancen dieser Strategiemaβnahmen angesprochen. Teil II beschäftigt sich mit den Aquivalenzen zwischen GMP (Good Manufacturing Practice), EN 45001, ISO Guide 25, GLP (Good Laboratory Practice) und der Modellnorm DIN EN ISO 9001.
Infektionsmarker bei Blutspenden
Authors: Glück D. , Maurer C. , Kubanek B.
Published: June 2009

Ziel: Die Infektionsrisiken durch Blutpräparate sollen aus aktuellen Daten abgeschätzt werden. Design: Die Häufigkeiten der Infektionsmarker HIV, HCV und HBV unter den Blutspenden wurden erfaβt. Rahmen und Teilnehmen Durch das Studiensekretariat konnten die Befunde bei alien Blutspenden im Jahr 1994 erstmals aus alien staatlichkommunalen und DRK-Blutspendediensten in Deutschland erfaβt und ausgewertet werden. Ergebnisse: Das Risiko einer Infektionsübertragung durch zelluläre Blutpräparate aus Mehrfachspenden ist einzuschätzen als 1 : 1 Million für HIV mit einem Streubereich von 1: 300000 bis 1 : 3 Millionen und für HBV 1: 50000. Für HCV ist das Risiko für den Gesamtbereich noch nicht endgültig festzustellen, liegt jedoch sicher unter 1 : 20 000. Aus Teildaten der Serokonversion von HCV bei Blutspendern aus ländlichen Bereichen errechnen sich sogar Zahlen von kleiner 1 : 200000. Schluβfolgerungen: Durch die effektive Spender-selektion, für HIV seit 1985, für HCV seit 1990, ist ein hohes Maβ an Sicherheit erreicht.