bluuebunny/crossref_metadata_2025 huggingface dataset:
Designed Ankyrin Repeat Proteins as Anti‐Idiotypic‐Binding Molecules
Authors: VOGEL MONIQUE , KELLER‐GAUTSCHI ELSBETH , BAUMANN MICHAEL J. , AMSTUTZ PATRICK , RUF CHRISTINE , KRICEK FRANZ , STADLER BEDA M.
Published: September 2007

Abstract:  According to the network theory antibodies may act as antigens thus generating anti‐idiotypic antibodies that can function as regulators of immune responses. Designed ankyrin repeat proteins (DARPins) are a new class of binding proteins and may serve as an alternative to antibodies. Selections from large DARPin libraries against the variable regions of a murine monoclonal anti‐human IgE antibody, termed BSW17, yielded two highly specific anti‐idiotypic DARPins both with high affinity. Their binding characteristics were comparable with these of a previously selected anti‐idiotypic antibody. In vitro cell assays showed that the anti‐idiotypic DARPins were able to inhibit the binding of BSW17 to cell‐bound IgE and prevented BSW17 functional activity. These experiments demonstrate the possibility to isolate anti‐idiotypic DARPins recognizing idiotypic determinants analogous to antibodies. In the future these DARPins may be further analyzed for their potential as putative vaccine candidates.
SLAM‐Associated Protein Solves a Mystery of Autoimmunity
Authors: SAWADA SHIGEMASA , TAKEI MASAMI , ISHIWATA TETSUYOSI , SHIRAIWA HIDETAKA , INOMATA HIROTAKE , NOZAKI TAKAMASA
Published: September 2007

Abstract:  SLAM‐associated protein (SAP) is essential for viral protection, lifelong immune memory (vaccination), and lifelong autoantibody production. We discuss how SAP is a key player in the development of autoimmune disease.
Standardization of Autoimmune Diagnostics in Germany
Authors: SACK ULRICH , CONRAD KARSTEN , CSERNOK ELENA , FRANK INGRID , HAASS MICHAEL , KRIEGER THORSTEN , SEYFARTH MICHAEL , SCHLOSSER UDO , SCHMIDT REINHOLD E. , WITTE TORSTEN
Published: September 2007

Abstract:  The German Regional Group of EASI was established during the annual Meeting of the German Society of Immunology in Kiel in September 2005. Since this initial informative meeting, an active core group of about a dozen rheumatologists, immunologists, and laboratory specialists has been generating starter projects. In general, these projects do focus on clinically associated diagnostic questions, and do integrate a variety of specialists with profound knowledge in several related subjects. The aims of the German EASI group are to contribute to the definition of standards and to improve patient care. Therefore, the group is establishing guidelines for the diagnosis of autoimmune diseases, to standardize and improve their quality, combining the experience of clinical and laboratory specialists. The diagnostic activities focus currently on systemic lupus erythematosus (SLE) and on rheumatoid arthritis. These activities include laboratory investigations and diagnosis through clinical manifestations. Standardized diagnostics cannot be based solely on vague symptoms and positive laboratory tests. In laboratory diagnostics, standardization and implementation of objective methods for the detection of autoantibodies has been identified as a central challenge. Here, immune fluorescence techniques and the evaluation of RibP are used as first parameters that could improve SLE diagnostics. Furthermore, guidelines and proposals from scientific medical organizations, and in particular from other national EASI groups will be adapted to the German health system. A cornerstone of implementation is the identification and logistic preparation of existing serum banks, the definition of gaps that should be bridged, and, particularly, the definition and collection of adequate control groups. Through these measures, the German EASI group will provide a standardized diagnostic model of autoimmune disorders throughout Europe starting in the field of rheumatology. Diagnostics may become more rational, efficient, faster, and cost‐efficient. Patients with autoimmune rheumatic disorders will profit from receiving an earlier and more accurate diagnosis, which again will allow earlier therapeutic intervention and lead to a better long‐term clinical outcome.
Autoimmunity and Time Entanglement
Authors: POO JUAN I. , MARTIN PABLO I. , REWALD ENRIQUE
Published: September 2007

Abstract:  Time is an important factor for every patient affected by chronic inflammatory autoimmune disease. More often than not we cannot predict the natural outcome of the process neither determine whether a remission depends on a particular treatment schedule or it does depend on the restoring capability by the “health drive.” Autoimmune manifestations appear to be entangled with time in most complex ways.
The Pro‐ and Anti‐Inflammatory Potential of Interleukin‐12
Authors: CHANG HYUN‐DONG , RADBRUCH ANDREAS
Published: September 2007

Abstract: T helper (Th) lymphocytes, upon activation and differential costimulation, differentiate into various types of Th memory cells with distinct functions. Upon activation in the presence of interleukin‐12 (IL‐12), Th1 memory cells are imprinted for the expression of interferon‐γ (IFN‐γ), by genetic modification of theifnγ gene and expression of the transcription factor T‐bet. Th1 cells are potent inducers of chronic inflammation of tissues expressing their cognate (auto)antigen. Here, we discuss an anti‐inflammatory potential of Th1 cells, based on their expression of IL‐10. While the expression of IFN‐γ in memory Th1 cells is independent of the original inducer IL‐12, IL‐12 is and remains required to induce expression of the regulatory cytokine IL‐10 by Th1 memory cells giving IL‐12 the potential to act anti‐inflammatory during secondary responses.
Role of Toll‐like Receptors in HMGB1 Release from Macrophages
Authors: PISETSKY DAVID S. , JIANG WEIWEN
Published: September 2007

Abstract:  HMGB1 is a nonhistone nuclear protein that can serve as a cytokine and activate innate immunity. The translocation of this molecule from the inside to the outside of cells is a critical event in inflammation, occurring following activation of certain Toll‐like receptors (TLRs) as well as during the course of apoptotic as well as necrotic cell death. Because the kinetics of HMGB1 release differs from that of a conventional cytokine, it provides a broader therapeutic window and may be an important new target of therapy for inflammatory, autoimmune, and infectious diseases.
EASI—The European Autoimmunity Standardisation Initiative
Authors: SHOENFELD YEHUDA , CERVERA RICARD , HAASS MICHAEL , KALLENBERG CEES , KHAMASHTA MUNTHER , MERONI PIERLUIGI , PIETTE JEAN‐CHARLES , SCHMIDT REINHOLD , WIIK ALLAN
Published: September 2007

Abstract:  The European Autoimmunity Standardisation Initiative (EASI) was founded 6 years ago with the intention of improving diagnostics in chronic rheumatic disorders by strengthening the collaboration between clinical and laboratory scientists responsible for autoimmune diagnostics at any given level of the health care systems in Europe. Thorough clinical work‐up is frequently not the basis for the usage of laboratory tests. Old established test methods may be exchanged for new methods without the differences being communicated. Often, the optimal way of reporting laboratory results to the clinic has not been agreed upon between clinicians and laboratory scientists. An EASI international team consisting of expert rheumatologists/internists/laboratory scientists from Denmark, France, Germany, Israel, Italy, the Netherlands, Spain, and the United Kingdom meets once a year to discuss how interactions between laboratories and rheumatology clinics could be improved in practical terms, how algorithms for cost‐effective and rational autoantibody testing could be harmonized, and what an international concept of standardization in this area could look like. In national EASI teams, which were founded in many European countries, clinical and laboratory experts also meet regularly to discuss how European guidelines may lead to practical improvements in their recent country‐specific approaches. To enable the exchange of information and experiences, representatives of the different teams of the EASI Network will meet annually in the EASI Forum. All EASI teams will present and discuss the results of their activities with other experts in the field in an EASI Conference, which will be held biannually at the International Congress on Autoimmunity.
Screening of Endothelial Expression Libraries for the Identification of Novel Autoantigens Involved in Distinct Autoimmune Diseases Characterized by Endothelial Dysfunction
Authors: MARGUTTI PAOLA , DELUNARDO FEDERICA , COLASANTI TANIA , PIRO ETTORE , PROFUMO ELISABETTA , RIGANÒ RACHELE , SIRACUSANO ALESSANDRA , BUTTARI BRIGITTA , CONTI FABRIZIO , ALESSANDRI CRISTIANO , CAPOZZI ANTONELLA , SORICE MAURIZIO , ORTONA ELENA
Published: September 2007

Abstract:  Screening a cDNA expression library is a powerful technique that allows identification of previously uncharacterized antigens. Proteins recognized by antibodies from patients with autoimmune diseases have been intensively studied over the past two decades since cDNAs encoding autoantigens have become available. Identity of many of them has been defined, and specific structural motifs or post‐translational modifications, which may be important to explain the generation of such antibodies during the autoimmune process, have been pointed out. The screening of human umbilical artery or microvascular endothelial cell expression libraries appears to be a useful tool for the characterization of endothelial autoantigens allowing us to identify several molecules recognized from serum anti‐endothelial cell antibodies of patients with diseases characterized by immune‐mediated endothelial dysfunctions.
Antigen Preparation for Immunological Studies in Systemic Autoimmune Diseases
Authors: ZAMPIERI SANDRA , GHIRARDELLO ANNA , ROSSINI KATIA , IACCARINO LUCA , BASSI NICOLA , ATZENI FABIOLA , SARZI‐PUTTINI PIERCARLO , DORIA ANDREA
Published: September 2007

Abstract:  Systemic autoimmune diseases are characterized by the presence in patient sera of high titers of autoantibodies directed against self‐antigens. The characterization of specific autoantigen–autoantibody system is very important for research as well as for diagnostic tools and several techniques can be employed in such immunological studies. In this review an overview of the different biochemical methods of antigen preparation and the specific methodological applications is given, also describing potential critical aspects and benefits of the different protocols.
Diagnostic Accuracy of IgA Anti‐Tissue Transglutaminase Antibody Assays in Celiac Disease Patients with Selective IgA Deficiency
Authors: VILLALTA D. , ALESSIO M. G. , TAMPOIA M. , TONUTTI E. , BRUSCA I. , BAGNASCO M. , PESCE G. , BIZZARO N.
Published: September 2007

Abstract:  Clinical studies have estimated a 10‐ to 20‐fold increased risk for celiac disease (CD) in patients with selective IgA deficiency (SIgAD). For this reason, screening for CD is mandatory in SIgAD patients, but it represents a special challenge since the specific IgA class antibodies against gliadin (AGA), endomysium (EMA), and tissue‐transglutaminase (tTG) are not produced in patients with CD. IgG class counterparts of these antibodies may be informative; in particular IgG EMA has been demonstrated to be a valid marker for diagnosing CD in SIgAD cases, but it is not used much in clinical laboratories, because it is cumbersome and involves some technical difficulties. Even if it was widely used in clinical laboratories, the measuring of IgG AGA has shown a less‐than‐optimum diagnostic accuracy, so that now it tends to be substituted by tests for anti‐tTG IgG, for which the few available studies have shown diagnostic performances superior to AGA. Since it is not known whether various available methods for measuring IgG anti‐tTG antibodies offer similar diagnostic performances, we have compared the results obtained from nine second‐generation commercial methods (D‐tek, Phadia, Immco, Orgentec, Radim, Euroimmun, Inova, Aesku, Generic Assays), measuring IgG anti‐tTG antibodies in 20 patients with CD and SIgAD and in 113 controls (9 patients with SIgAD without CD, 54 patients with chronic liver disease, and 50 healthy individuals). Diagnostic sensitivity, calculated by means of ROC plot analysis, ranged between 75% and 95%, and specificity ranged from 94% to 100%. In the same population, the diagnostic sensitivity and specificity of AGA IgG were 40% and 87%, respectively. Even though they perform differently, all IgG anti‐tTG methods evaluated are reliable serological assays for the diagnosis of CD in SIgAD patients, with diagnostic accuracy superior to the AGA IgG method. The methods that use a mix of tTG and gliadin peptides as the antigenic preparation have a specificity slightly lower than that of the methods that use only tTG.
Serological and Clinical Characterization of Anti‐dsDNA and Anti‐PM/Scl Double‐Positive Patients
Authors: MAHLER M. , GREIDINGER E. L. , SZMYRKA M. , KROMMINGA A. , FRITZLER M. J.
Published: September 2007

Abstract:  Antibodies to double‐stranded desoxyribonucleic acid (dsDNA) and to the polymyositis/scleroderma (PM/Scl) complex are regarded as serological markers for systemic lupus erythematosus (SLE) and PM/Scl overlap syndrome, respectively. In a previous study, serum samples were identified that contained antibodies specific for both dsDNA and PM/Scl. Fourteen of these sera were available for more detailed investigation including the autoantibody profile as determined by several methods including an addressable laser bead assay, Crithidia luciliae indirect immunofluorescence test (CLIFT) and a PM1‐Alpha ELISA. Moreover, 300 samples from connective tissue disease patients and 30 PM/Scl positive samples were screened for anti‐dsDNA+/PM/Scl+ specimens by CLIFT, dsDNA ELISA, and PM1‐Alpha ELISA. We confirmed anti‐dsDNA and anti‐PM/Scl reactivity in 2/7 samples from the previous study. One sample had also anti‐chromatin and anti‐SS‐A reactivity and the second sample was oligoreactive. In addition, 2/300 (0.7%) unselected samples from connective tissue disease patients were identified with anti‐dsDNA and anti‐PM/Scl reactivity. In a panel of PM1‐Alpha positive samples (n= 30) collected regardless of the diagnosis of the patients, no anti‐dsDNA reactivity was found. All anti‐dsDNA+/anti‐PM/Scl+ patients identified fulfilled sufficient criteria to be classified as definite SLE and also had at least one feature of systemic sclerosis (i.e., sclerodactyly and/or Raynaud's phenomenon). Only 1/4 patients had clinical evidence of dermatomyositis. The combination of anti‐dsDNA+/anti‐PM/Scl+ in patients suffering from connective tissue disease is less frequently found than previously described when newer assays are used. Clinically, anti‐dsDNA+/anti‐PM/Scl+ patients may define a small subgroup of SLE patients with additional features of systemic sclerosis.
Performance of Antinuclear Antibody Connective Tissue Disease Screen
Authors: LÓPEZ‐HOYOS MARCOS , RODRÍGUEZ‐VALVERDE VICENTE , MARTINEZ‐TABOADA VICTOR
Published: September 2007

Abstract:  Antinuclear antibodies (ANAs) have become routine laboratory parameters in clinical hospitals. However, ANA testing by indirect immunofluorescence (IIF) assays is not an automated laboratory test. Efforts are being made to develop easy and semi‐ or automated methods to screen for ANAs. We evaluated the clinical performance of a new ELISA developed to screen for connective tissue disease related ANAs. The presence of serum ANA was studied with a commercial ELISA (Varelisa ANA CTD Screen) in 472 patients (202 SLE, 41 Sjögren syndrome, 11 CREST, 59 rheumatoid arthritis, 30 seronegative spondyloarthropaties, 77 inflammatory bowel disease, 13 reactive arthritis, 11 giant cell arteritis, 28 ankylosing spondilitis). A hundred and five sera from healthy subjects were used as controls. Receiver operator characteristics (ROC) analysis was carried out in order to optimize the cutoff. At target specificities of 80/90%, sensitivities of 80.8/ 73.9% were achieved. At the manufacturer's cutoff (ratio ≥1.0) sensitivity/specificity of 71.4/91.2% was found. At that cutoff, a positive likelihood ratio of 8.11 was found. For helping in the diagnosis of connective tissue diseases a test employing a subset of the most prevalent specificities reveals a good compromise as indicated by a high‐positive likelihood ratio. However, the presence of ANAs in pathologies other than connective tissue diseases, such as SLE or Sjögren syndrome, may be of clinical significance as well. In these cases an IIF assay test is still mandatory, especially in autoimmune laboratories.
Evaluation of Current Methods for the Measurement of Serum Anti–Double‐Stranded DNA Antibodies
Authors: GHIRARDELLO ANNA , VILLALTA DANILO , MOROZZI GABRIELLA , AFELTRA ANTONELLA , GALEAZZI MAURO , GERLI ROBERTO , MATHIEU ALESSANDRO , MERONI PIER LUIGI , MIGLIORINI PAOLA , RADICE ANTONELLA , RICCIERI VALERIA , RUFFATTI AMELIA , SEBASTIANI GIAN DOMENICO , TINCANI ANGELA , DORIA ANDREA ,   ON BEHALF OF FIRMA GROUP
Published: September 2007

Abstract:  Autoantibodies to double‐stranded DNA (dsDNA) are, by definition, serological markers of systemic lupus erythematosus. However, the clinical value of anti‐dsDNA antibodies largely depends on the assay principle and analytical variables of the methods used to quantitate and immunologically characterize them. In the present article, an overview of current methods for anti‐dsDNA antibody detection is presented, together with a look at the future trends in technologies newly employed in this field.
Evaluation of the FIDIS Vasculitis Multiplex Immunoassay for Diagnosis and Follow‐up of ANCA‐Associated Vasculitis and Goodpasture's Disease
Authors: DAMOISEAUX J. , VAESSEN M. , KNAPEN Y. , CSERNOK E. , STEGEMAN C. A. , VAN PAASSEN P. , COHEN TERVAERT J. W.
Published: September 2007

Abstract:  We have evaluated a new‐multiplex immunoassay (FIDIS Vasculitis) for simultaneous detection and quantification of anti‐MPO, ‐PR3, and ‐glomerular basement membrane (GBM) antibodies in diagnosis and follow‐up of ANCA‐associated vasculitides (AAV) and Goodpasture's disease. ANCA were determined in sera of (a) 87 consecutive patients with biopsy‐proven pauci‐immune NCGN and 72 controls; (b) 9 patients with Goodpasture's disease; and (c) 60 WG patients and 60 controls, previously used in a multicenter comparison of direct and capture ELISA for PR3‐ANCA. Finally, for prediction of relapses, PR3‐ANCA was measured in samples preceding relapse in 23 PR3‐AAV patients and in 23 matched PR3‐AAV patients without relapse. The relative sensitivity of the FIDIS Vasculitis assay was 97.4% for MPO‐ANCA and 92.3% for PR3‐ANCA; specificity was 100% and 97.2%, respectively. Evaluation of the anti‐GBM antibody detection revealed a sensitivity of 100% and a specificity of 99.6%. The sensitivity for WG of the PR3‐ANCA detection (71.6%) approached the performance of capture ELISA (74%), although at the cost of specificity (96.7% versus 100%). For prediction of relapses a rise of 50% in ANCA level by FIDIS Vasculitis appeared optimal (ROC curve) for prediction of relapses. However, as compared to capture ELISA, both positive (63% versus 76%) and negative (68% versus 72%) predictive values were reduced. In conclusion, simultaneous detection of anti‐MPO, ‐PR3, and ‐GBM antibodies in the multiplex FIDIS Vasculitis assay has excellent performance in terms of diagnosis of patients with AAV or Goodpasture's disease. However, detection of rises in PR3‐ANCA for prediction of relapses gives less optimal results when compared to capture ELISA.
Development of Automated Assays for Anticardiolipin Antibodies Determination: Addressing Antigen and Standardization Issues
Authors: CAPUANO FRANCESCO , GRASSO VALENTINA , BELFORTE LUCA , PALLAVICINI LUCA , TINCANI ANGELA , ANDREOLI LAURA , BONELLI FABRIZIO
Published: September 2007

Abstract:  The lack of reliable standardization tools as well as the poorly defined nature of the “Cardiolipin antigen” makes the development of the anticardiolipin antibody (ACA) assays (for anti‐IgG and IgM detection) highly challenging. This article describes how several issues have been solved during the development of an automated ACA immunoassays, based on a technology that includes paramagnetic microbeads as solid‐phase reagents and chemiluminescence as a signal. The technology is adapted to an automatic immunoanalyzer, called LIAISON, which performs, in an automatic manner, the whole assay, starting from the primary tube of the bleeding to the display of the assay result. Briefly, the magnetic microbeads were coated with an ethanolic solution of cardiolipin (CL) followed by an affinity‐purified, cross‐linked human β2‐glycoprotein I. CL‐coated paramagnetic microbeads, after incubation with an ACA‐positive sera plus addition of immunogold‐protein A, were visualized by SEM, showing the presence of well‐defined protein clusters on the microbeads surface as an indication of the successful occurrence of the “antigen” coating. The assay standardization was achieved on the basis of human samples containing various amount of ACA, which were previously classified according to consensus doses. The evaluation of the optimized LIAISON Cardiolipin assays (IgG and IgM) was conducted by using clinically characterized APS sera. The results of the evaluation showed that the LIAISON assays perform at least similar to certain well‐established ACA enzyme‐linked immunosorbent assay (ELISA) products.
Clinical Evaluation of a New Quantitative Enzyme‐Linked Immunosorbent Assay for Detection of Double‐Stranded DNA Autoantibodies
Authors: BARDIN NATHALIE , RAGOT CÉLINE , SANMARCO MARIELLE
Published: September 2007

Abstract:  The measurement of autoantibodies specific for double‐stranded DNA (anti‐dsDNA) is a useful tool for the diagnosis and the prognosis of systemic lupus erythematosus (SLE). A new quantitative enzyme‐linked immunosorbent assay (ELISA), ORG anti‐dsDNA, is recently available for the determination of anti‐dsDNA antibodies. The aim of this study was to evaluate the clinical performance of this new assay in a cohort of SLE patients. Seventy‐five sera from SLE patients were tested by two methods for anti‐dsDNA determination, ORG anti‐dsDNA, and EliA anti‐dsDNA. Normal controls were 60 sera from healthy subjects. Moreover, 37 sera from patients with non‐SLE connective tissue diseases were tested in parallel. The levels of complement components (C3, C4, CH50) were measured by nephelometry. From SLE patients, 91% were positive against 9% in non‐SLE patients and 2% in healthy subjects. The sensitivity, specificity, and Youden test for SLE were 90%, 98%, and 88%, respectively. The Yule test (1%) indicated a close association with the disease. The comparison with EliA anti‐dsDNA showed a moderate concordance between the two tests in the group of SLE (κ= 0.51) and a good concordance in the non‐SLE group (κ= 0.89). A significant inverse correlation was found with complement components levels, biological markers associated with disease activity. Our results show this new assay as sensitive and specific for the diagnosis of SLE. Moreover, the correlation with markers associated with disease activity makes it promising for clinical use.
Practice Prize Report—An Assortmentwide Decision-Support System for Dynamic Pricing and Promotion Planning in DIY Retailing
Authors: Natter Martin , Reutterer Thomas , Mild Andreas , Taudes Alfred
Published: September 2007

The main objective of this report is to describe a decision-support system for dynamic retail pricing and promotion planning. Our weekly demand model incorporates price, reference price effects, seasonality, article availability information, features, and discounts. Building on previous research, we quantify demand interdependencies and integrate the resulting profit-lifting effects into the optimal pricing model. The methodology was developed and implemented at bauMax, an Austrian do-it-yourself retailer. Along with the practical requirements, an objective function was employed that can be used as a vehicle for implementing a retailer’s strategy. Eight pricing rounds with thousands of different stock-keeping units have each served as a testing ground for our approach. Based on various benchmarking methods, a positive impact on profit was reported. The currently implemented marketing decision-support system increased gross profit on average by 8.1 and sales by 2.1%.
The 2005 ISMS Practice Prize Winner—Customer Equity and Lifetime Management (CELM) Finnair Case Study
Authors: Tirenni Giuliano , Labbi Abderrahim , Berrospi Cesar , Elisseeff André , Bhose Timir , Pauro Kari , Pöyhönen Seppo
Published: September 2007

The Customer Equity and Lifetime Management (CELM) solution is based on a decision-support system that offers marketing managers a scientific framework for the optimal planning and budgeting of targeted marketing campaigns to maximize return on marketing investments. The CELM technology combines advanced models of Markov decision processes (MDPs), Monte Carlo simulation, and portfolio optimization. MDPs are used to model customer dynamics and to find optimal marketing policies that maximize the value generated by a customer over a given time horizon. Lifetime value optimization is achieved through dynamic programming algorithms that identify which marketing actions, such as cross-selling, up-selling, and loyalty marketing campaigns, transition customers to better value and loyalty states. The CELM technology can also be used to simulate the financial impact of a given marketing policy using Monte Carlo simulation. This allows marketing managers to simulate several targeting scenarios to assess budget requirements and the expected impact of a given marketing policy. The benefits of the solution are illustrated with the Finnair case study, where CELM has been used to optimize marketing planning and budgeting for Finnair’s frequent-flyer program (FFP).
Editorial—It’s the Findings, Stupid, Not the Assumptions
Authors: Shugan Steven M.
Published: September 2007

Observing reality is especially valuable. However, without models, every situation at every time on every variable would be unpredictable. Assumptions allow models and theories to assert constancy. Assumptions distill and simplify reality by dismissing the conspicuous but irrelevant. Criticizing assumptions as unrealistic is absurd. Abstraction is the precise virtue of an assumption. For example, seldom are we prisoners facing interrogation, yet the prisoner’s dilemma remains relevant. The adage “A bird in the hand is worth two in the bush” is relevant for more than birds. Unrealistic assumptions that deny current beliefs breed great new theories.

Assumptions are analogous to the basic ingredients in a gourmet recipe. Only the final product of the recipe dictates whether the ingredients suffice. Similarly, assumptions are realistic when they produce good theories, satisfactory predictions, valuable implications, and correct recommendations. Output matters far more than input. Realism is only an issue when creatively diagnosing poorly performing models, not when judging model performance.

Assumptions are the source of value in empirical analyses. If data sets were truly the source of value, empirical research studies would only greatly devalue the raw data by dramatically reducing rich observations to a few meager summary statistics or estimated parameters. Most empirical research makes a contribution by ignoring (assuming away) most information in the data.

We must dramatically shift our attention far away from the hopeless pursuit and sophistry of realistic assumptions to the contribution those assumptions produce. There are scientific methods for evaluating model output (i.e., predictions, findings, implications, recommendation) on criteria such as accuracy, reliability, validity, robustness, and so on. No corresponding objective scientific methods exist for evaluating realism. Realism depends only on personal taste.
Charnley low-friction arthroplasty
Authors: Wroblewski B. M. , Siney P. D. , Fleming P. A.
Published: September 2007

We studied survival to 38 years after Charnley low-friction arthroplasty of the hip. We used revision as an end-point, while adopting a policy of regular follow-up and early revision for radiological changes alone if indicated.

Between November 1962 and June 2005, 22 066 primary low-friction arthroplasties (17 409 patients) had been performed at Wrightington Hospital by more than 330 surgeons. By June 2006, 1001 (4.5%) hips had been revised and 1490 patients (2662 hips, 12%) had died. At 31 years, where a minimum of 40 hips were still attending follow-up, survival with revision for infection as an endpoint was 95%, for dislocation 98%, for a fractured stem 88.6%, for a loose stem 72.5% and for a loose acetabular component 53.7%. Wear and loosening of the ultra-high-molecular-weight polyethylene acetabular component were the main long-term problems.

We conclude that regular follow-up after hip replacement is essential and that all operative findings should be recorded at revision.
Posterior cruciate ligament balancing in total knee replacement
Authors: Christen B. , Heesterbeek P. V. , Wymenga A. , Wehrli U.
Published: September 2007

We have examined the relationship between the size of the flexion gap and the anterior translation of the tibia in flexion during implantation of a posterior cruciate ligament (PCL)-retaining BalanSys total knee replacement (TKR). In 91 knees, the flexion gap and anterior tibial translation were measured intra-operatively using a custom-made, flexible tensor-spacer device.

The results showed that for each increase of 1 mm in the flexion gap in the tensed knee a mean anterior tibial translation of 1.25 mm (SD 0.79, 95% confidence interval 1.13 to 1.37) was produced.

When implanting a PCL-retaining TKR the surgeon should be aware that the tibiofemoral contact point is related to the choice of thickness of the polyethylene insert. An additional thickness of polyethylene insert of 2 mm results in an approximate increase in tibial anterior translation of 2.5 mm while the flexed knee is distracted with a force of between 100 N and 200 N.
Revision anterior cruciate ligament reconstruction
Authors: Ohly N. E. , Murray I. R. , Keating J. F.
Published: September 2007

We reviewed 87 patients who underwent revision reconstruction of the anterior cruciate ligament. The incidence of meniscal tears and degenerative change was assessed and related to the interval between failure of the primary graft and revision reconstruction. Patients were divided into two groups: early revision surgery within six months of graft failure, and delayed revision. Degenerative change was scored using the French Society of Arthroscopy system.

There was a significantly higher incidence of articular cartilage degeneration in the delayed group (Mann-Whitney U-test, 53.2% vs 24%, p < 0.01). No patient in the early group had advanced degenerative change, compared to 9.2% of patients in the delayed group. There was no significant difference (Mann-Whitney U-test, p = 0.3) in the incidence of meniscal tears between the two groups.

We conclude that revision reconstruction should be carried out within six months of primary graft failure, in order to minimise the risk of degenerative change.
Vacuum-mixing cement does not decrease overall porosity in cemented femoral stems
Authors: Messick K. J. , Miller M. A. , Damron L. A. , Race A. , Clarke M. T. , Mann K. A.
Published: September 2007

The role of vacuum mixing on the reduction of porosity and on the clinical performance of cemented total hip replacements remains uncertain. We have used paired femoral constructs prepared with either hand-mixed or vacuum-mixed cement in a cadaver model which simulated intra-operative conditions during cementing of the femoral component. After the cement had cured, the distribution of its porosity was determined, as was the strength of the cement-stem and cement-bone interfaces.

The overall fraction of the pore area was similar for both hand-mixed and vacuum-mixed cement (hand 6%; vacuum 5.7%; paired t-test, p = 0.187). The linear pore fractions at the interfaces were also similar for the two techniques. The pore number-density was much higher for the hand-mixed cement (paired t-test, p = 0.0013). The strength of the cement-stem interface was greater with the hand-mixed cement (paired t-test, p = 0.0005), while the strength of the cement-bone interface was not affected by the conditions of mixing (paired t-test, p = 0.275). The reduction in porosity with vacuum mixing did not affect the porosity of the mantle, but the distribution of the porosity can be affected by the technique of mixing used.
The use of gravity or manual-stress radiographs in the assessment of supination-external rotation fractures of the ankle
Authors: Schock H. J. , Pinzur M. , Manion L. , Stover M.
Published: September 2007

Supination-external rotation (SER) fractures of the ankle may present with a medial ligamentous injury that is not apparent on the initial radiographs. A cadaver gravity-stress view has been described, but the manual-stress view is considered to be the examination of choice for the diagnosis of medial injuries. We prospectively compared the efficacy of these two examinations.

We undertook both examinations in 29 patients with SER fractures. Of these, 16 (55%) were stress-positive, i.e. and had widening of the medial clear space of > 4 mm with a mean medial clear space of 6.09 mm (4.4 to 8.1) on gravity-stress and 5.81 mm (4.0 to 8.2) on manual-stress examination, and 13 patients (45%) were stress-negative with a mean medial clear space of 3.91 mm (3.3 to 5.1) and 3.61 mm (2.6 to 4.5) on examination of gravity- and manual-stress respectively. The mean absolute visual analgoue scale score for discomfort in the examination of gravity stress was 3.45 (1 to 6) and in the manual-stress procedure 6.14 (3 to 10).

We have shown that examination of gravity-stress is as reliable and perceived as more comfortable than that of manual stress. We recommend using it as the initial diagnostic screening examination for the detection of occult medial ligamentous injuries in SER fractures of the ankle.
Arthroscopic treatment of femoroacetabular impingement secondary to paediatric hip disorders
Authors: Ilizaliturri V. M. , Nossa-Barrera J. M. , Acosta-Rodriguez E. , Camacho-Galindo J.
Published: September 2007

Open reduction of the prominence at the femoral head-neck junction in femoroacetabular impingement has become an established treatment for this condition. We report our experience of arthroscopically-assisted treatment of femoroacetabular impingement secondary to paediatric hip disease in 14 hips in 13 consecutive patients (seven women, six men) with a mean age of 30.6 years (24 to 39) at the time of surgery. The mean follow-up was 2.5 years (2 to 4).

Radiologically, 13 hips had successful restoration of the normal geometry and only one had a residual deformity. The mean increase in the Western Ontario McMasters Osteoarthritis Index for the series at the last follow-up was 9.6 points (4 to 14). No patient developed avascular necrosis or sustained a fracture of the femoral neck or any other complication.

These findings suggest that femoroacetabular impingement associated with paediatric hip disease can be treated safely by arthroscopic techniques.
Cementless fixation of megaprostheses using a conical fluted stem in the treatment of bone tumours
Authors: Bruns J. , Delling G. , Gruber H. , Lohmann C. H. , Habermann C. R.
Published: September 2007

We reviewed 25 patients in whom a MUTARS megaprosthesis with a conical fluted stem had been implanted. There were three types of stem: a standard stem was used in 17 cases (three in the proximal femur, nine in the distal femur and five proximal tibia), a custom-made proximal femoral stem in four cases and a custom-made distal femoral stem in four cases. The mean age of the patients was 40.1 years (17 to 70) and the mean follow-up was for 2.5 years (0.9 to 7.4).

At follow-up two patients had died from their disease: one was alive with disease and 22 were disease-free. One of 23 prostheses had been removed for infection and another revised to a cemented stem. The mean Musculoskeletal Tumor Society score was 24.9 (12 to 30) and the mean Karnofsky index was 82% (60% to 100%).

There was no radiological evidence of loosening or subsidence. Stem stress shielding was seen in 11 patients and was marked in five of these.

There were five complications, rupture of the extensor mechanism of the knee after extra-articular resection in two patients, deep venous thrombosis in one, septic loosening in one, and dislocation of the hip in one.

The survival rate after seven years was 87% (95% confidence interval (CI) 83 to 91) for the patients and 95% (95% CI 91 to 99) for the megaprosthesis. A longer follow-up is needed to confirm these encouraging results.
Some Reflections on the General Meeting's Power to Control Corporate Proceedings
Authors: Qu Charles Zhen
Published: September 2007

The jurisprudence on the power of the general meeting of a company to control corporate actions has been developed largely through the courts' interpretation of various versions of constitutional provisions on corporate power allocation, all of which can be traced back to the Companies Act 1862 (UK), Table A, reg. 55. This body of jurisprudence is likely to be resorted to when a need for resolving a similar question arises, regardless of how the power allocation provision is worded under the current model company constitution in the relevant jurisdiction. This article discusses two different schools of views on corporate power allocation. The mainstream view is that where the management power is vested in the directors, it is not a matter where the general meeting can intervene. However, the author feels that this view is doctrinally unsustainable. Instead, the author agrees with the view that the general meeting's power to make management, and hence corporate litigation, decisions is determined by the parties' intention manifested in the words in all forms of company regulations. This article also argues that regardless of how the relevant constitutional provision on division of corporate powers is worded, the general meeting has power to act where a board that is capable of making impartial decisions is unavailable.
Trabecular Structure Quantified With the MRI-Based Virtual Bone Biopsy in Postmenopausal Women Contributes to Vertebral Deformity Burden Independent of Areal Vertebral BMD
Authors: Ladinsky Glenn A , Vasilic Branimir , Popescu Andra M , Wald Michael , Zemel Babette S , Snyder Peter J , Loh Louise , Song Hee Kwon , Saha Punam K , Wright Alexander C , Wehrli Felix W
Published: September 2007

In postmenopausal women with a wide range of vertebral deformities, MRI-based structural measures of topology and scale at the distal radius are shown to account for as much as 30% of vertebral deformity, independent of integral vertebral BMD.

Introduction: Trabecular bone architecture has been postulated to contribute to overall bone strength independent of vertebral BMD measured by DXA. However, there has thus far been only sparse in vivo evidence to support this hypothesis.

Materials and Methods: Postmenopausal women, 60-80 yr of age, were screened by DXA, and those with T-scores at either the hip or spine falling within the range of −2.5 ± 1.0 were studied with the MRI-based virtual bone biopsy, along with heel broadband ultrasound absorption and pQCT of the tibia. The data from 98 subjects meeting the enrollment criteria were subjected to νMRI at the distal tibia and radius, and measures of topology and scale of the trabecular bone network were computed. A spinal deformity index (SDI) was obtained from morphometric measurements in midline sagittal MR images of the thoracic and lumbar spine to evaluate associations between structure and deformity burden.

Results: A number of structural indices obtained at the distal radius were correlated with the SDI. Among these were the topological surface density (a measure of trabecular plates) and trabecular bone volume fraction, which were inversely correlated with SDI (p < 0.0001). Combinations of two structural parameters accounted for up to 30% of the variation in SDI (p < 0.0001) independent of spinal BMD, which was not significantly correlated. pQCT trabecular BMD was also weakly associated, whereas broadband ultrasound absorption was not. No significant association between SDI and structural indices were found at the tibia.

Conclusions: Structural measures at the distal radius obtained in vivo by νMRI explained a significant portion of the variation in total spinal deformity burden in postmenopausal women independent of areal BMD.
Comparison of Field Testing with Laboratory Testing of the Durability of Stone
Authors: Bortz S. A. , Powers Laura , Wonneberger Bernhard
Published: September 2007

Samples of three granites (Texas Pink, Mount Airy White, Academy Black), one marble (Carrara) and Indiana Limestone have been exposed to 11 years of natural weathering on the roof of a building in the Chicago area. Twice a year, the samples are visually reviewed. In addition, the changes in physical properties have been monitored using non-destructive test procedures for determination of the dynamic (sonic) modulus of elasticity. The sonic modulus measurements were recorded using procedures as outlined in ASTM C 215, “Standard Test Method for Fundamental Transverse, Longitudinal, and Torsional Frequencies of Concrete Specimens.” The sonic modulus measurements were compared to measurements of similar stone samples that were exposed to laboratory accelerated weathering testing. The exposed and protected surfaces have recently been examined petrographically, and the changes due to the natural weathering recorded. Based on this additional testing and evaluation, conclusions can be drawn which further indicate the use of accelerated weathering. Testing can effectively evaluate the long-term changes in the mechanical and physical properties of dimension stone when exposed to natural weathering.
Genetic disorders in the GH–IGF-I axis in mouse and man
Authors: Walenkamp M J E , Wit J M
Published: September 2007

Animal knockout experiments have offered the opportunity to study genes that play a role in growth and development. In the last few years, reports of patients with genetic defects in GH–IGF-I axis have greatly increased our knowledge of genetically determined causes of short stature. We will present the animal data and human reports of genetic disorders in the GH–IGF-I axis in order to describe the role of the GH–IGF-I axis in intrauterine and postnatal growth. In addition, the effects of the GH–IGF-I axis on the development and function of different organ systems such as brain, inner ear, eye, skeleton, glucose homeostasis, gonadal function, and immune system will be discussed. The number of patients with genetic defects in the GH–IGF-I axis is small, and a systematic diagnostic approach and selective genetic analysis in a patient with short stature are essential to identify more patients. Finally, the implications of a genetic defect in the GH–IGF-I axis for the patient and the therapeutic options will be discussed.
IGF-I treatment of insulin resistance
Authors: McDonald Anna , Williams Rachel M , Regan Fiona M , Semple Robert K , Dunger David B
Published: September 2007

Severe insulin resistance resulting from known or putative genetic defects affecting the insulin receptor or post-insulin receptor signalling represents a clinical spectrum ranging from Donohue’s and Rabson–Mendenhall syndrome, where the genetic defect is identified, through to the milder phenotype of type A insulin resistance, where a genetic defect can only be detected in around 10% of cases. Paradoxically, subjects with these conditions may present with hypoglycaemia due to mismatch of post-prandial glucose excursion and compensatory hyperinsulinaemia. Ultimately, treatment with insulin and insulin sensitisers will be unsuccessful and subjects may succumb to diabetes or its complications. Recombinant human IGF-I alone or combined with its binding protein (IGFBP-3) provides an alternative therapy as IGF-I receptor shares structural and functional homology with the insulin receptor and recombinant human insulin-like growth factor I (rhIGF-I) therapy could improve glucose disposal by signalling through the IGF-I receptor, whilst reducing the adverse effects of high insulin concentrations. There are also data which indicate that IGF-I signalling through the IGF-I receptor on the pancreatic β-cell may be important in maintaining insulin secretion. Pilot studies confirmed that rhIGF-I could reduce glucose and insulin levels in subjects with type A insulin resistance and those with Rabson–Mendenhall syndrome with sustained beneficial effects on HbA1c. Continued study has confirmed efficacy of rhIGF-I when combined with IGFBP-3 in the treatment of Donohue’s and type A insulin resistance subjects. Observations that IGF-I treatment can improve C-peptide levels in these subjects may indicate that it might be more valuable as a first line intervention to preserve β-cell function, rather than its current use as a medication of last resort in subjects where all other therapies have failed.
An Experimental Study and a Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Antisecretory Activity ofLactobacillus acidophilusStrain LB Against Nonrotavirus Diarrhea
Authors: Liévin-Le Moal Vanessa , Sarrazin-Davila Luis E. , Servin Alain L.
Published: September 2007

OBJECTIVE. Previous studies have shown that selected strains of Lactobacillus have the capacity to antagonize rotavirus-induced diarrhea. However, only a few reports have documented their efficacy against nonrotavirus diarrhea. This study involved an experimental investigation and a clinical trial of the antisecretory activity of Lactobacillus acidophilus strain LB in the context of nonrotavirus diarrhea.

METHODS. The activity of a culture of L acidophilus LB or of the lyophilized, heat-killed L acidophilus LB bacteria plus their spent culture medium was tested in inhibiting the formation of fluid-formed domes in cultured human intestinal Caco-2/TC7 cell monolayers infected with diarrheagenic, diffusely adhering Afa/Dr Escherichia coli C1845 bacteria. A randomized, double-blind, placebo-controlled clinical trial of male or female children who were 10 months of age and presented with nonrotavirus, well-established diarrhea was conducted to evaluate the therapeutic efficacy of a pharmaceutical preparation that contains 10 billion heat-killed L acidophilus LB plus 160 mg of spent culture medium.

RESULTS. Infection of the cells with C1845 bacteria that were treated with L acidophilus LB culture or the lyophilized, heat-killed L acidophilus LB bacteria plus their culture medium produced a dosage-dependent decrease in the number of fluid-formed domes as compared with cells that were infected with untreated C1845 bacteria. The clinical results show that in selected and controlled homogeneous groups of children with well-established, nonrotavirus diarrhea, adding lyophilized, heat-killed L acidophilus LB bacteria plus their culture medium to a solution of oral rehydration solution shortened by 1 day the recovery time (ie, the time until the first normal stool was passed) as compared with children who received placebo oral rehydration solution.

CONCLUSIONS. Heat-killed L acidophilus LB plus its culture medium antagonizes the C1845-induced increase in paracellular permeability in intestinal Caco-2/TC7 cells and produces a clinically significant benefit in the management of children with nonrotavirus, well-established diarrhea.