bluuebunny/crossref_metadata_2025 huggingface dataset:
Total-Variation Regularization Based Inverse Planning for Intensity Modulated Arc Therapy
Authors: Zhu Lei , Niu Tianye , Choi Kihwan , Xing Lei
Published: January 2013

Intensity modulated arc therapy (IMAT) delivers conformal dose distributions through continuous gantry rotation with constant or variable speed while modulating the field aperture shape and weight. The enlarged angular space and machine delivery constraints make inverse planning of IMAT more intractable as compared to its counterpart of fixed gantry IMRT. Currently, IMAT inverse planning is being done using two extreme methods: the first one computes in beamlet domain with a subsequent arc leaf sequencing, and the second proceeds in machine parameter domain with entire emphasis placed on a pre-determined delivery method without exploring potentially better alternative delivery schemes. Towards truly optimizing the IMAT treatment on a patient specific basis, in this work we propose a total-variation based inverse planning framework for IMAT, which takes advantage of the useful features of the above two existing approaches while avoiding their shortcomings. A quadratic optimization algorithm has been implemented to demonstrate the performance and advantage of the proposed approach. Applications of the technique to a prostate case and a head and neck case indicate that the algorithm is capable of generating IMAT plans with patient specific numbers of arcs efficiently. Superior dose distributions and delivery time are achieved with a maximum number of apertures of three for each field. As compared to conventional beamlet-based algorithms, our method regularizes the field modulation complexity during optimization, and permits us to obtain the best possible plan with a pre-set modulation complexity of fluences. As illustrated in both prostate and head-and-neck case studies, the proposed method produces more favorable dose distributions than the segment-based algorithms, by optimally accommodating the clinical need of intensity modulation levels for each individual field. On a more fundamental level, our formulation preserves the convexity of optimization and makes the search of the global optimal solution possible with a deterministic method.
Graphical Methods for Reliability Data
Authors: Surucu Baris , Sazak Hakan S.
Published: January 2013

In this article, we review some existing nonparametric and parametric graphical methods for reliability data. We first give general definitions and concepts in the area. Then, we discuss some well‐known basic graphical techniques including empirical cumulative distribution function (cdf) plot, hazard plot, probability‐probability (P‐P) plot, quantile‐quantile (Q‐Q) plot, the Weibull plot, the Duane plot, mean cumulative function (MCF) plot, and Total Time on Test (TTT) plot. We also describe some problem‐specific graphical techniques that explore different applications in the reliability area.
Double productive immunoglobulin sequence rearrangements in patients with chronic lymphocytic leukemia
Authors: Visco Carlo , Moretta Francesca , Falisi Erika , Facco Monica , Maura Francesco , Novella Elisabetta , Nichele Ilaria , Finotto Silvia , Giaretta Ilaria , Ave Elisa , Perbellini Omar , Guercini Nicola , Scupoli Maria Teresa , Trentin Livio , Trimarco Valentina , Neri Antonino , Semenzato Gianpietro , Rodeghiero Francesco , Pizzolo Giovanni , Ambrosetti Achille
Published: January 2013

The immunoglobulin heavy chain variable (IGHV) gene mutational status represents a major prognostic marker in chronic lymphocytic leukemia (CLL). Usually, the prognostic implications of IGHV gene analysis can be reliably ascertained but, occasionally, double productive rearrangements have been detected. Clinical presentation and biological features of such cases are unknown. Sixty patients with morphologically and phenotypically monoclonal CLL but double productive IGHV rearrangements were retrospectively identified by mRNA analysis from three Hematology Institutions. Clinical and biological features and survival of these 60 patients were compared with a control group of patients with CLL and single IGHV rearrangement. A prospective registry was used to assess the epidemiology of double productive IGHV among incidental patients with CLL. Using standard criteria to define IGHV‐mutated (M) or unmutated (U) cases, 39 of the 60 patients (65%) with double productive IGHV rearrangement had concordant status (23 MM, 16 UU), while 21 (35%) had discordant IGHV status. As compared with M patients, the MM ones had lower CD38 expression, more favorable cytogenetics and more indolent clinical behavior. Cases with UU had similar characteristics of U patients. Discordant cases presented with adverse prognostic features and had an aggressive clinical behavior requiring early treatment, similar to U patients. The prevalence of double IGHV was 3.1%. Patients with CLL with double concordant mutational status (MM or UU) have a clinical course similar to that of the corresponding single IGHV status, while those exhibiting discordant status represent a high risk population. This may help correct stratification within clinical trials. Am. J. Hematol. 88:277–282, 2013. © 2013 Wiley Periodicals, Inc.
Conducting Organic Frameworks Based on a Main‐Group Metal and Organocyanide Radicals
Authors: Zhang Zhongyue , Zhao Hanhua , Kojima Hirotaka , Mori Takehiko , Dunbar Kim R.
Published: January 2013

Reactions of the main‐group cation TlI with anions of 2,5‐derivatives of TCNQ (TCNQ=7,7,8,8‐tetracyanoquinodimethane) have led to the isolation of a family of unprecedented semiconducting main‐group‐metal–organic frameworks, namely, [Tl(TCNQX2)], (X=H, Cl, Br, I). A comparison of single‐crystal and powder X‐ray diffraction data revealed the existence of a third polymorph of the previously reported material Tl(TCNQ)] and two distinct polymorphs of [Tl(TCNQCl2)], whereas only one phase was identified for [Tl(TCNQBr2)] and [Tl(TCNQI2)]. These new results are described in the context of the structures of other known binary metal–TCNQ frameworks that display a variety of coordination environments for the central cation, namely, four‐, six‐, and eight‐coordinate, and different arrangements of the adjacent TCNQ radicals—parallel versus perpendicular—in the stacked columns. The halogen substituents affect the structures and the properties of these compounds, owing to both steric and electronic effects as evidenced by the semiconducting properties of crystals of [Tl(TCNQCl2)] phase I, [Tl(TCNQBr2)], and [Tl(TCNQI2)], which correlate well with the distances of adjacent TCNQ radicals in the columns. 1D infinite Hückel model simulations of the band structures of [Tl(TCNQCl2)] phase I, [Tl(TCNQBr2)], and [Tl(TCNQI2)] were conducted with and without consideration of the TlI cations, the results of which indicate that the charge mobility does not strictly occur in one dimension. The modulations of the band structures with various assumptions of the energy difference (Δ) between the TlI 6s orbital and the TCNQ LUMO orbital were calculated and are discussed in light of the observed properties.
Examination of measurement apparatus for 2D magnetic properties
Authors: Maeda Yoshitaka , Urata Shinya , Kano Yuko , Arakawa Toshinobu , Yanase Shunji , Okazaki Yasuo , Watanabe Shota
Published: January 2013

The development of highly efficient electrical rotating machines is an important issue in energy conservation. To realize this goal, we must consider the details of magnetic phenomena in rotating machines. Therefore, an accurate evaluation of 2D magnetic properties is indispensable. However, it is very difficult to measure these properties, especially under high magnetic induction, due to the difficulty in measuring rotating magnetic properties in electrical steel sheets. In this paper, a new apparatus with an eight‐tooth‐core, distributed windings, and interpoles, is proposed in order to measure 2D magnetic properties. We evaluate the uniformity of magnetic conditions in specimens by finite element analysis. © 2013 Wiley Periodicals, Inc. Electron Comm Jpn, 96(2): 57–64, 2013; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.10403
Stable position of a B12 cluster near the Si surface and its STM images
Authors: Ito Shunsuke , Maruizumi Takuya , Suwa Yuji
Published: January 2013

We conducted a first‐principles examination to determine the most stable position of an icosahedral B12 cluster near a Si(001) surface. We discovered that such a cluster is most stable when its center is located at the fourth layer position from the Si top surface where a Si dimer sits directly overhead. Scanning tunneling microscopy (STM) simulation revealed that Si dimers above the B12 cluster are distinguishable from other dimers in STM images at low sample bias voltages. © 2013 Wiley Periodicals, Inc. Electron Comm Jpn, 96(2): 50–56, 2013; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.10405
Tetranuclear Copper Azido Complex of 4,5‐Diazafluoren‐9‐one
Authors: Babu B. Kishore , Biju A. R. , Sunkari Sailaja , Rajasekharan M. V. , Tuchagues J. ‐P.
Published: January 2013

A tetranuclear CuII complex, Cu4(dafone)4(N3)8 (1, dafone = 4,5‐diazafluoren‐9‐one) is described. The propensity of dafone to chelate through one short and one long bond is readily accommodated by the tendency of CuII to undergo Jahn–Teller elongation in its six‐coordinate complexes. The crystal structure of 1 consists of two distortion isomers of the tetranuclear complex molecule. In each isomer, there are four μ1,1‐azido bridges and two μ1,1,1‐azido bridges as well as two terminally coordinated azide ions. The isomers, both of which are centrosymmetric, differ in the way the Jahn–Teller axes of the different CuII sites are aligned. Magnetic susceptibility measurements show an overall ferromagnetic interaction, which could be fitted with a two parameter model (J1 = 22.8 cm–1, J3 = –8.2 cm–1). The magnetic interaction was modelled by using DFT calculations, which showed that the two isomers are magnetically quite different; one is a ferromagnetically coupled tetramer, and the other may be viewed as two ferromagnetic dimers. The X‐band EPR spectra are in broad agreement with this model.
Pressure Effect Studies on the Spin‐Transition Behavior of a Dinuclear Iron(II) Compound
Authors: Bhattacharjee Ashis , Roy Madhusudan , Ksenofontov Vadim , Kitchen Jonathan A. , Brooker Sally , Gütlich Philipp
Published: January 2013

Magnetic studies into the effect of different hydrostatic pressures between ambient and 1.03 GPa on the high‐spin (HS) ⇄ low‐spin (LS) transition behavior of the dinuclear iron(II) compound [FeII2(PMAT)2](BF4)4·DMF (1, PMAT = 4‐amino‐3,5‐bis{[(2‐pyridylmethyl)amino]methyl}‐4H‐1,2,4‐triazole, DMF = N,N‐dimethylformamide) have been carried out at 2–300 K. Under ambient pressure, the sample studied exhibits a [HS–HS] to [HS–LS] half spin transition (ST) at T${1 \over 2}$ = 208 K without any thermal hysteresis. Increasing the pressure above 0.2 GPa causes an increase (initially rapid but above 0.5 GPa more gradual) of T${1 \over 2}$ as well as a matching reduction in the residual high‐spin fraction at room temperature. This paper probes in detail how the increased pressure favors the stabilization of the system through a transition from the [HS–HS] state to the [HS–LS] state, although there is no evidence of the [LS–LS] state even under a pressure of 1.03 GPa and down to 2 K. This work includes magnetic measurements, a calorimetric study of the ST behavior, and an estimation of the entropy change for such a half‐ST process. The origin of [HS–HS] ⇄ [HS–LS] transition behavior, which likely lies with the rigidness of the bridging ligand, is explained in greater detail. This is consistent with significant stabilization of the [HS–LS] form by the two very rigid bridging ligands between the two FeII centers. The role of intermolecular interactions in the stabilization of the dinuclear lattice system is established.
Regulation of sodium and calcium in Daphnia magna exposed to silver nanoparticles
Authors: Zhao Chun-Mei , Wang Wen-Xiong
Published: January 2013

The toxicity of manufactured silver nanoparticles (AgNPs) has been widely studied, but the influence of AgNPs on the major ions (such as sodium [Na] and calcium [Ca]) regulations are unknown. In the present study, a freshwater cladoceran Daphnia magna was exposed to commercial AgNPs coated with polyvinylpyrrolidone. After 48 h, the Na body content was significantly reduced by AgNO3 exposure, but the Ca body content was significantly increased under AgNO3 and AgNP exposures, respectively. No effect was observed on the body concentrations of Na and Ca at 50 to 500 µg/L AgNPs with 1-µM cysteine addition. Exposure of AgNO3 and AgNPs inhibited the Na influx and elevated the Na efflux. In contrast, their exposure increased the Ca influx, but did not affect the Ca efflux. The results of the present study demonstrated the significant influences of AgNO3 and AgNPs (without cysteine) on Na and Ca regulations. Such effect of AgNPs on Na and Ca regulation disappeared after cysteine addition, indicating that the soluble Ag released from AgNPs played a major role in the ionoregulatory dysfunction. Environ. Toxicol. Chem. 2013;32:913–919. © 2013 SETAC
Expression of immunoregulatory genes and its relationship to lead exposure and lead-mediated oxidative stress in wild ungulates from an abandoned mining area
Authors: Rodríguez-Estival Jaime , de la Lastra José M. Pérez , Ortiz-Santaliestra Manuel E. , Vidal Dolors , Mateo Rafael
Published: January 2013

Lead (Pb) is a highly toxic metal that can induce oxidative stress and affect the immune system by modifying the expression of immunomodulator-related genes. The aim of the present study was to investigate the association between Pb exposure and the transcriptional profiles of some cytokines, as well as the relationship between Pb exposure and changes in oxidative stress biomarkers observed in the spleen of wild ungulates exposed to mining pollution. Red deer and wild boar from the mining area studied had higher spleen, liver, and bone Pb levels than controls, indicating a chronic exposure to Pb pollution. Such exposure caused a depletion of spleen glutathione levels in both species and disrupted the activity of antioxidant enzymes, suggesting the generation of oxidative stress conditions. Deer from the mining area also showed an induced T-helper (Th)–dependent immune response toward the Th2 pathway, whereas boar from the mining area showed a cytokine profile suggesting an inclination of the immune response toward the Th1 pathway. These results indicate that environmental exposure to Pb may alter immune responses in wild ungulates exposed to mining pollution. However, evidence of direct relationships between Pb-mediated oxidative stress and the changes detected in immune responses were not found. Further research is needed to evaluate the immunotoxic potential of Pb pollution, also considering the prevalence of chronic infectious diseases in wildlife in environments affected by mining activities. Environ. Toxicol. Chem. 2013;32:876–883. © 2013 SETAC
Integrated analysis of genome‐wide copy number alterations and gene expression in microsatellite stable, CpG island methylator phenotype‐negative colon cancer
Authors: Loo Lenora W. M. , Tiirikainen Maarit , Cheng Iona , Lum‐Jones Annette , Seifried Ann , Church James M. , Gryfe Robert , Weisenberger Daniel J. , Lindor Noralane M. , Gallinger Steven , Haile Robert W. , Duggan David J. , Thibodeau Stephen N. , Casey Graham , Le Marchand Loïc
Published: January 2013

Microsatellite stable (MSS), CpG island methylator phenotype (CIMP)‐negative colorectal tumors, the most prevalent molecular subtype of colorectal cancer, are associated with extensive copy number alteration (CNA) events and aneuploidy. We report on the identification of characteristic recurrent CNA (with frequency >25%) events and associated gene expression profiles for a total of 40 paired tumor and adjacent normal colon tissues using genome‐wide microarrays. We observed recurrent CNAs, namely gains at 1q, 7p, 7q, 8p12‐11, 8q, 12p13, 13q, 20p, 20q, Xp, and Xq and losses at 1p36, 1p31, 1p21, 4p15‐12, 4q12‐35, 5q21‐22, 6q26, 8p, 14q, 15q11‐12, 17p, 18p, 18q, 21q21‐22, and 22q. Within these genomic regions we identified 356 genes with significant differential expression (P < 0.0001 and ±1.5‐fold change) in the tumor compared to adjacent normal tissue. Gene ontology and pathway analyses indicated that many of these genes were involved in functional mechanisms that regulate cell cycle, cell death, and metabolism. An amplicon present in >70% of the tumor samples at 20q11‐20q13 contained several cancer‐related genes (AHCY, POFUT1, RPN2, TH1L, and PRPF6) that were upregulated and demonstrated a significant linear correlation (P < 0.05) for gene dosage and gene expression. Copy number loss at 8p, a CNA associated with adenocarcinoma and poor prognosis, was observed in >50% of the tumor samples and demonstrated a significant linear correlation for gene dosage and gene expression for two potential tumor suppressor genes, MTUS1 (8p22) and PPP2CB (8p12). The results from our integration analysis illustrate the complex relationship between genomic alterations and gene expression in colon cancer. © 2013 Wiley Periodicals, Inc.
High‐resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non‐hodgkin's lymphoma
Authors: Aya‐Bonilla Carlos , Green Michael R. , Camilleri Emily , Benton Miles , Keane Colm , Marlton Paula , Lea Rod , Gandhi Maher K. , Griffiths Lyn R.
Published: January 2013

We employed a Hidden‐Markov‐Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high‐density single nucleotide polymorphism (SNP) array data from Non‐Hodgkin's lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B‐cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B‐cells (i.e., BCR, MAPK, and PI3K signaling), its role in B‐cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down‐regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over‐representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over‐representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B‐cell lymphomas. © 2013 Wiley Periodicals, Inc.
Nuclear remodeling of telomeres in chronic myeloid leukemia
Authors: Samassekou Oumar , Hébert Josée , Mai Sabine , Yan Ju
Published: January 2013

Chronic myeloid leukemia (CML) is a hematologic cancer characterized by the proliferation of myeloid cells and the translocation between chromosomes 9 and 22, [t(9;22)(q34.1;q11.2)]. At the chronic phase (CP), CML cells present longer telomeres than at the other clinical phases, display arm‐specific maintenance of individual telomere lengths, and are chromosomally stable. We asked whether an alteration of nuclear organization of telomeres, which is associated with genomic instability, occurs in CML cells at the CP. We used fluorescent in situ hybridization of telomeres combined with three‐dimensional (3D) quantification to study the nuclear telomeric architecture of CML cells at the CP. We found that cells can exhibit high telomere numbers, different telomere distributions, and alterations in peripheral or central nuclear location of telomeres. Also, we show that CML cells can be categorized in two groups according to the number of their telomere aggregates (TAs). We propose that the presence of high TAs in some samples is associated with the increased genomic instability and could be an indication of the clinical transitional phase. Also, alterations of nuclear organization of telomeres at the CP confirm that nuclear remodeling of telomeres can occur at an early clinical stage of a cancer. © 2013 Wiley Periodicals, Inc.
Coupling of ultrasound‐assisted extraction and expanded bed adsorption for simplified medicinal plant processing and its theoretical model: Extraction and enrichment of ginsenosides from Radix Ginseng as a case study
Authors: Mi Jianing , Zhang Min , Zhang Hongyang , Wang Yuerong , Wu Shikun , Hu Ping
Published: January 2013

A high‐efficient and environmental‐friendly method for the preparation of ginsenosides from Radix Ginseng using the method of coupling of ultrasound‐assisted extraction with expanded bed adsorption is described. Based on the optimal extraction conditions screened by surface response methodology, ginsenosides were extracted and adsorbed, then eluted by the two‐step elution protocol. The comparison results between the coupling of ultrasound‐assisted extraction with expanded bed adsorption method and conventional method showed that the former was better than the latter in both process efficiency and greenness. The process efficiency and energy efficiency of the coupling of ultrasound‐assisted extraction with expanded bed adsorption method rapidly increased by 1.4‐fold and 18.5‐fold of the conventional method, while the environmental cost and CO2 emission of the conventional method were 12.9‐fold and 17.0‐fold of the new method. Furthermore, the theoretical model for the extraction of targets was derived. The results revealed that the theoretical model suitably described the process of preparing ginsenosides by the coupling of ultrasound‐assisted extraction with expanded bed adsorption system.
Reactive Template Synthesis of Polypyrrole Nanotubes for Fabricating Metal/Conducting Polymer Nanocomposites
Authors: Zhang Jun , Liu Xianghong , Zhang Lixue , Cao Bingqiang , Wu Shihua
Published: January 2013

Unique nanocomposites of polypyrrole/Au and polypyrrole/Pt hybrid nanotubes are synthesized employing polypyrrole (PPy) nanotubes as an advanced support by solution reduction. The conducting polymer PPy nanotubes are fabricated by using pre‐prepared MnO2 nanowires as the reactive templates. MnO2 nanowires induce the 1D polymerization of pyrrole monomers and the simultaneous dissolution of the templates affords the hollow tube‐like structure. The loading content of metal nanoparticles in the nanocomposites could be adjusted by simply changing the amount of metal precursors. This work provides an efficient approach to fabricate an important kind of metal/conducting polymer hybrid nanotubes that are potentially useful for electrocatalyst and sensor materials.
The menopause: risks and benefits of available treatments
Authors: Currie Heather , Cochrane Rosemary
Published: January 2013

Menopausal symptoms affect many woman, but debate continues over the role of hormone replacement therapy in their management. Our Drug review considers the risks and benefits of the current treatment options, followed by an analysis of the prescription data and sources of further information.
Properties and use of compound analgesics in pain management
Authors: Chaplin Steve , Campbell William
Published: January 2013

Steve Chaplin and Dr William Campbell provide an overview of the properties of compound analgesics and how they compare in the management of pain.
A Framework for Continuous Inspection Plans Using Multivariate Mathematical Methods
Authors: Oprime Pedro , Ganga Gilberto Miller Devós
Published: January 2013

The aim of this study was to propose and apply a sampling procedure using mathematical models and multivariate statistics for continuous processes in manufacturing companies. The research presented in this paper can be classified as a descriptive and empirical quantitative study in which the basic interest was in creating a model that describes and analyzes the causal relationships between the quality characteristics (in this case, multivariate) of a process, in order to select the best continuous inspection plan. This framework was applied in a company that supplies the main component producers for the worldwide car industry. The results obtained from applying the multivariate procedures made it possible to select the best continuous inspection plan based on inspection frequency, resultant mean quality, and proportion of the units inspected. This procedure should be tested on new problems and real situations in order to validate the methods used. Copyright © 2012 John Wiley & Sons, Ltd.
Adapting the Hypervolume Quality Indicator to Quantify Trade‐offs and Search Efficiency for Multiple Criteria Decision Making Using Pareto Fronts
Authors: Lu Lu , Anderson‐Cook Christine M.
Published: January 2013

When choosing a best solution based on simultaneously balancing multiple objectives, the Pareto front approach allows promising solutions across the spectrum of user preferences for the weightings of the objectives to be identified and compared quantitatively. The shape of the complete Pareto front provides useful information about the amount of trade‐off between the different criteria and how much compromise is needed from some criterion to improve the others. Visualizing the Pareto front in higher (3 or more) dimensions becomes difficult, so a numerical measure of this relationship helps capture the degree of trade‐off. The traditional hypervolume quality indicator based on subjective scaling for multiple criteria optimization method comparison provides an arbitrary value that lacks direct interpretability. This paper proposes an interpretable summary for quantifying the nature of the relationship between criteria with a standardized hypervolume under the Pareto front (HVUPF) for a flexible number of optimization criteria, and demonstrates how this single number summary can be used to evaluate and compare the efficiency of different search methods as well as tracking the search progress in populating the complete Pareto front. A new HVUPF growth plot is developed for quantifying the performance of a search method on completeness, efficiency, as well as variability associated with the use of random starts, and offers an effective approach for method assessment and comparison. Two new enhancements for the algorithm to populate the Pareto front are described and compared with the HVUPF growth plot. The methodology is illustrated with an optimal screening design example, where new Pareto search methods are proposed to improve computational efficiency, but is broadly applicable to other multiple criteria optimization problems. Copyright © 2012 John Wiley & Sons, Ltd.
Reliability Analysis into Hospital Dialysis System: A Case Study
Authors: Tsarouhas Panagiotis H.
Published: January 2013

Dialysis system is an artificial medical operating system that works as a kidney in the human body, and is used when the kidney has failed or has been spoiled. In this study, reliability and maintainability analysis, which are of the fundamental issues for the operation management of a dialysis system, was developed. Descriptive statistics of all the failures at each device of the system were determined. The failure data covers a period of 45 months. The best fit of the failure data between the common theoretical distributions was found, and the respective parameters were identified. Moreover, the reliability and the maintainability at device and system level for different time intervals were calculated. They both proved to be useful tools to assess the current situation, and to predict reliability, mainly in the short term, for upgrading the operation management of the system. Copyright © 2012 John Wiley & Sons, Ltd.
Adoption of Hip Resurfacing Arthroplasty at Hospital for Special Surgery: A Cohort Study
Authors: Su Edwin P. , Su Sherwin L.
Published: January 2013

Background

Hip resurfacing arthroplasty (HRA) is an alternative to traditional total hip replacement (THR) that allows for the preservation of femoral bone. It is a more technically difficult procedure that has led some researchers to report an unsatisfactory learning curve (Berend et al., J Bone Joint Surg Am Suppl 2:89–92, 2011 ; Mont et al., Clin Orthop Relat Res 465:63–70, 2007 ).

Purpose

The purpose of this study was to investigate the adoption of HRA at our institution, examining the clinical results, revision rate, and modes of failure. Additionally, a comparison of three different implant systems was performed.

Methods

A retrospective review of a consecutive series of HRA performed at our institution between the years 2004 and 2009 was carried out. A total of 820 HRA with a minimum of 2 years of follow-up were included in the study. The majority of included patients were males (70%), with osteoarthritis (92%). The average age was 49.8 years, and the mean BMI was 27.5 kg/m2.

Results

The average Harris hip score improved from 61 to 96.5 postoperatively. Thirteen revisions (1.6%) were performed for femoral neck fracture, femoral head osteonecrosis, acetabular loosening, metal reactivity/metallosis, and metal allergy. The overall Kaplan–Meier survival curve with revision surgery as an endpoint showed 98.5% survival at 5 years. There were no observable differences in clinical scores or revision rates between the different implant systems.

Conclusions

HRA can be successfully adopted with a low complication rate, given careful patient selection, specialized surgical training, and use of good implant design.
Novel Treatment of a Failed Quadriceps Tendon Repair in a Diabetic Patient Using a Patella-Quadriceps Tendon Allograft
Authors: Druskin Sasha C. , Rodeo Scott A.
Published: January 2013

Recurrent quadriceps tendon rupture is a debilitating condition that may be challenging to treat, especially in the presence of systemic disease such as diabetes mellitus (Bedi et al., J Shoulder Elbow Surg 19:978–988, 2010; Chbnou and Frenette, Am J Physiol Regul Integr Comp Physiol 5:R952–R957, 2004; Chen et al., J Shoulder Elbow Surg 5:416–421, 2003). Many surgical treatment protocols have been proposed (Azar, in Canale and Beatty, eds., Campbell's Operative Orthopedics, Mosby/Elsevier, Philadelphia, PA, 2008; Ilan et al., J Am Acad Orthop Surg 3:192–200, 2003; Rodeo and Izawa, in Garrett et al., eds., Principles and Practice of Orthopedic Sports Medicine, Lippincott Williams & Wilkins, Philadelphia, PA, 2000). We report the case of a diabetic male with multiple treatment failures. He ultimately sustained a good outcome following treatment with a novel surgical technique that utilized a patella quadriceps tendon allograft. Tendon allograft-to-native bone healing had previously failed in this patient, so we used a bone-tendon construct allograft to provide an allograft bone-to-native bone healing site. Now, 13 months postoperative, the patient has increased strength, minimal pain, 20 ° of extensor lag and 130 ° of flexion.
Effect of Pelvic Osteotomy in the Skeletally Immature on Acetabular Coverage
Authors: Al-Moussa Sulaiman , Moroz Paul , Beaulé Paul E.
Published: January 2013

Background

Although pelvic osteotomy in children has been effective in re-establishing containment of the hip joint, its impact on hip joint development with respect to acetabular coverage is ill defined.

Purpose

The purpose of this study is to determine the prevalence of acetabular overcoverage in patients who had pelvic osteotomy during childhood and its impact on patient function.

Patients and Methods

Between 1980 and 2008, all patients who had a pelvic osteotomy done at our institution for non-neuropathic hip dysplasia (DDH) or secondary to Legg–Calvé–Perthes disease (LCP) prior to skeletal maturity were reviewed. A clinical assessment and the WOMAC, UCLA Activity Score, Marx activity score, and SF-36 quality-of-life questionnaires were completed. A standardized AP pelvic X-ray was performed to determine the acetabular coverage, signs of retroversion, and degenerative changes.

Results

Twenty-eight patients (32 hips) were identified, of which 14 (9 DDH, 5 LCP) agreed to participate. Impingement sign was positive in eight patients (six DDH, two LCP). Crossover and ischial spine signs were each present in ten hips. Tonnis grades were: 0 in 1 hip, 1 in 10 hips, 2 in 2 hips, and 3 in 1 hip. The mean Tonnis angle was 11.6 ± 8.6°. The mean CE angle was 24.0 ± 15.9° with six hips having a CE angle <20° and one hip with a CE angle >40°. There was no correlation between crossover sign or ischial sign and Tonnis grade ( p = 0.739), hip pain ( p = 0.520), or impingement sign ( p = 1.00).

Conclusions

Acetabular overcoverage is common in patients who underwent pelvic osteotomy during childhood. No correlation was identified between retroversion and hip pain in our patient cohort.
Labral Refixation: Current Techniques and Indications
Authors: Philippon Marc J. , Briggs Karen K. , Fagrelius Teddy , Patterson Dianna
Published: January 2013

Background

Labral tears have been associated with femoroacetabular impingement, instability, sports-related activity or trauma, capsular laxity or hypermobility, dysplasia, and degeneration. Disruption of the labrum increases the rate of acetabular cartilage compression and the contact stress between the femoral and acetabular cartilage. If left untreated, these lesions will alter normal hip joint function and may eventually lead to osteoarthritis.

Methods

For the labrum with adequate tissue (>7 mm), the labrum is repaired if it is detached or torn. If the labrum is bruised, a rim reduction and repair is performed, especially in the presence of cartilage damage and the labral–chondral junction. Labri are debrided only if there is enough substance to maintain the function of the labrum. Care must be taken to fix the labrum so that it provides adequate seal with the femoral head.

Results

Two-year outcome on 122 patients who underwent arthroscopic treatment for femoroacetabular impingement and chondrolabral dysfunction showed that, overall, most patients showed an improvement in symptoms and function and were satisfied with the results. Independent predictors of improved outcomes were joint space >2 mm and repair of labral pathology instead of debridement. Several other studies have shown excellent results following labral refixation and repair.

Conclusions

Labral tears have been associated with femoroacetabular impingement, instability, sports-related activity or trauma, capsular laxity or hypermobility, dysplasia, and degeneration. Untreated labral tears can result in premature osteoarthritis of the hip. Debridement only used to be the standard of care, but excellent results reveal arthroscopic labral repair and refixation are an option with good outcomes.
The Development and Validation of a More Discriminating Functional Hip Score for Research
Authors: Konan Sujith , Tahmassebi Jenni , Haddad Fares S.
Published: January 2013

Background

Total hip arthroplasty (THA) is a commonly performed procedure with increasing frequency in the young adult. While most available outcome measures can document postoperative improvement in pain and function, they do not measure the ability to perform high-demand activities.

Questions/Purposes

We present and validate a user-friendly discriminating hip scoring system (the functional hip score) for use in younger, “high-demand” patients undergoing hip arthroplasty surgery.

Methods

We studied 38 subjects without any hip symptoms and 72 patients undergoing THA for osteoarthritis of the hip. Preprocedure and postprocedure scores were collected in the latter cohort of patients. SF-36 and WOMAC scores were used to validate our functional scoring system. The functional hip score was tested for internal consistency, reliability, and criterion validity.

Results

The functional hip score had high test–retest reliability, internal consistency, and criterion validity. This can be used to measure functional outcome in the younger high-demand adult patient undergoing THA.

Conclusion

Our discriminating functional hip score can reliably measure improvement in hip function in the younger high-demand adult. Current scoring systems have ceiling effects and are unable to differentiate a high performing hip replacement from the routine hip replacement. The use of functional tasks that are measured objectively allows better documentation of improvement in hip function.
Caution Should be Taken in Performing Surgical Hip Dislocation for the Treatment of Femoroacetabular Impingement in Patients over the Age of 40
Authors: Boone G. R. , Pagnotto M. R. , Walker J. A. , Trousdale R. T. , Sierra R. J.
Published: January 2013

Background

Open and arthroscopic procedures are treatment options for patients with femoroacetabular impingement (FAI). Age has been found to be a predictive factor in the outcome of patients undergoing periacetabular osteotomy (PAO) for hip dysplasia. It is unclear if older age contraindicates joint preservation through a surgical hip dislocation (SHD).

Questions/Purpose

The purpose of this retrospective case series was to evaluate the short-term outcomes of patients over 40 years of age without radiographic evidence of end-stage arthritis who underwent SHD for the treatment of FAI and to determine whether older age should be a contraindication for joint-preserving procedures in these patients. Our specific aims included (1) documenting the intraoperative findings and procedures, (2) assessing pain relief provided, and (3) assessing treatment failures and postoperative complications, noting the number of patients that ultimately required total hip arthroplasty (THA).

Patients and Methods

All patients at age 40 and older who had SHD for the treatment of FAI were identified from a series of patients treated with SHD. Clinical notes, radiographs, and operative reports were reviewed to determine clinical results, complications, and the need for additional procedures. The minimum follow-up was 1 year (mean 3.9 years; range 1–8 years).

Results

At final follow-up, 11/22 (50%) of hips had pain relief, while 11/22 (50%) either continued having significant symptoms or required THA. Five (23%) reported nontrochanteric pain symptoms that were the same or worse than before surgery, and six hips (27%) underwent subsequent THA). The average time between SHD and THA was 1.9 years (0.9–6.2). The average age of patients who went on to require THA was 45 (42–50) years.

Conclusions

Surgical hip dislocation can be used for the treatment of FAI in patients over age 40, but strict selection criteria should be adhered to, as only half of the patients experienced significant improvement in their hip pain. THA was required in one-third of hips for continued pain and radiographic progression of arthritis. SHD for treatment of pathology that is not amenable to hip arthroscopy should remain a surgical option in older patients with FAI only if joint degeneration is not present.
Simultaneous versus Staged Bilateral Total Knee Arthroplasty
Authors: Hussain Nasir , Chien Teresa , Hussain Farrah , Bookwala Ammar , Simunovic Nicole , Shetty Vijay , Bhandari Mohit
Published: January 2013

Background

An important source of debate in many orthopaedic practices is the choice of performing simultaneous or staged bilateral total knee arthroplasty.

Questions/Purpose

The objective of this meta-analysis is to compare simultaneous bilateral with staged bilateral total knee arthroplasty for peri-operative complication rates, infection rates and mortality outcomes.

Methods

All relevant citations were retrieved from MEDLINE, EMBASE, COCHRANE databases and the unpublished literature. Included studies were assessed for methodological quality and abstracted data was conducted independently by two reviewers. Data was categorized into subgroups and pooled using the DerSimonian and Laird's random effects model.

Results

A total of 18 articles were identified from 873 potentially relevant titles and selected for inclusion in the primary meta-analyses. The incidence of mortality was significantly higher in the simultaneous group at 30 days (RR [relative risk] 3.67, 95% confidence interval [CI] 1.68–8.02, p = 0.001, I2 = 59%, n = 67,691 patients), 3 months (RR 2.45, 95% CI 2.15–2.79, p < 0.00001, I2 = 0%, n = 66,142 patients) and 1 year (RR 1.85, 95% CI 1.66–2.06, p < 0.001, I2 = 0%, n = 65,322 patients) after surgery. However, there were no significant differences between the two groups in regards to in-hospital mortality rates (R 1.18, 95% CI 0.74–1.88, p = 0.48, I2 = 0%, n = 33,814 patients). In addition, there was no increased risk of deep vein thrombosis, cardiac complication, and pulmonary embolism or infection rates in either comparison group.

Conclusions

The results of the analysis suggest that simultaneous bilateral total knee arthroplasty has a significantly higher rate of mortality at 30 days, 3 months and 1 year after surgery, but similar infection and complication rates in comparison to staged bilateral total knee arthroplasty.
Thrombophilic Abnormalities in Patients with or without Pulmonary Embolism following Elective Spinal Surgery
Authors: Kotwal Suhel , Kawaguchi Satoshi , Hughes Alexander , Cammisa Frank , Zhang Kai , Salvati Eduardo , Girardi Federico
Published: January 2013

Background

Significance of the thrombophilic abnormalities in development of venous thromboembolism (VTE) has been studies with total hip arthroplasty and acute traumatic spinal cord injury. However, their role as risk factors for VTE in elective spinal surgery remains to be determined.

Questions/Purposes

To determine the role of thrombophilic abnormalities in the development of pulmonary embolism (PE) following elective spine surgery.

Methods

Case and control groups were created in patients who had undergone elective spinal surgery for degenerative conditions. The PE group comprised 12 patients whose post-operative course was complicated by development of PE. The control group included 12 patients with an uneventful post-operative course. Demographic data including age, gender and surgical procedures were matched between the PE group and the control group. Both groups were evaluated for thrombophilic and hypofibrinolytic risk factors at 3 months post-operatively or later. Blood tests were performed to measure fasting serum homocysteine, antithrombin III, and protein C. Molecular genetic testing was conducted for detection of the plasminogen activator inhibitor-1 4G/4G, and prothrombin 3 UTR gene mutations.

Results

Heterozygous mutation (G20201A) of prothrombin was detected in two patients (16.7%) in the PE group, whereas no such mutation was noted in the control group. Plasminogen activator inhibitor-1 4G/4G homozygous mutation was seen in three in the PE group and two in the control group. Of homocysteine, antithrombin III and protein C, only one patient in each group showed abnormal levels of homocysteine. In total, there half of the patients in the PE group had at least one thrombophilic abnormality, whereas three (25%) patients showed such abnormality in the control group.

Conclusion

These findings suggest the involvement of thrombophilic abnormalities, especially the heterozygous G20201A mutation, in the development of PE in patients undergoing elective spinal surgery.
Lumbar Spine Intervertebral Disc Gene Delivery: A Pilot Study in Lewis Rats
Authors: Damle Sheela R. , Rawlins Bernard A. , Boachie-Adjei Oheneba , Crystal Ronald G. , Hidaka Chisa , Cunningham Matthew E.
Published: January 2013

Background

Basic research toward understanding and treating disc pathology in the spine has utilized numerous animal models, with delivery of small molecules, purified factors, and genes of interest. To date, gene delivery to the rat lumbar spine has only been described utilizing genetically programmed cells in a matrix which has required partial disc excision, and expected limitation of treatment diffusion into the disc.

Purpose

This study was designed to develop and describe a surgical technique for lumbar spine exposure and disc space preparation, and use of a matrix-free method for gene delivery.

Methods

Naïve or genetically programmed isogeneic bone marrow stromal cells were surgically delivered to adolescent male Lewis rat lumbar discs, and utilizing quantitative biochemical and qualitative immunohistological assessments, the implanted cells were detected 3 days post-procedure.

Results

Statistically significant differences were noted for recovery of the β-galactosidase marker gene comparing delivery of naïve or labeled cells (105 cells per disc) from the site of implantation, and between delivery of 105 or 106 labeled cells per disc at the site of implantation and the adjacent vertebral body. Immunohistology confirmed that the β-galactosidase marker was detected in the adjacent vertebra bone in the zone of surgical implantation.

Conclusions

The model requires further testing in larger cohorts and with biologically active genes of interest, but the observations from the pilot experiments are very encouraging that this will be a useful comparative model for basic spine research involving gene or cell delivery, or other locally delivered therapies to the intervertebral disc or adjacent vertebral bodies in rats.
Large‐scale isolation of human skeletal muscle satellite cells from post‐mortem tissue and development of quantitative assays to evaluate modulators of myogenesis
Authors: Scott Ian C. , Tomlinson Wendy , Walding Andrew , Isherwood Beverley , Dougall Iain G.
Published: January 2013

Background

During aging, there is a decreased ability to maintain skeletal muscle mass and function (sarcopenia). Such changes in skeletal muscle are also co‐morbidities of diseases including cancer, congestive heart failure and chronic obstructive pulmonary disease. The loss of muscle mass results in decreased strength and exercise tolerance and reduced ability to perform daily activities. Pharmacological agents addressing these pathologies could have significant clinical impact, but their identification requires understanding of mechanisms driving myotube formation (myogenesis) and atrophy and provision of relevant assays. The aim of this study was to develop robust in vitro methods to study human myogenesis.

Methods

Satellite cells were isolated by digestion of post‐mortem skeletal muscle and selection using anti‐CD56 MicroBeads. CD56+ cell‐derived myotubes were quantified by high content imaging of myosin heavy chains. TaqMan‐polymerase chain reaction arrays were used to quantify expression of 41 selected genes during differentiation. The effects of activin receptor agonists and tumour necrosis factor alpha (TNFα) on myogenesis and gene expression were characterised.

Results

Large‐scale isolation of CD56+ cells enabled development of a quantitative myogenesis assay with maximal myotube formation 3 days after initiating differentiation. Gene expression analysis demonstrated expression of 19 genes changed substantially during myogenesis. TNFα and activin receptor agonists inhibited myogenesis and downregulated gene expression of muscle transcription factors, structural components and markers of oxidative phenotype, but only TNFα increased expression of pro‐inflammatory markers.

Conclusions

We have developed methods for large‐scale isolation of satellite cells from muscle and quantitative assays for studying human myogenesis. These systems may prove useful as part of a screening cascade designed to identify therapeutic agents for improving muscle function.

Electronic supplementary material

The online version of this article (doi:10.1007/s13539‐012‐0097‐z) contains supplementary material, which is available to authorized users.