bluuebunny/crossref_metadata_2025 huggingface dataset:
Antitopoisomerase 1 Antibodies in Systemic Sclerosis
Authors: TAMBY MATHIEU C. , BUSSONE GUILLAUME , MOUTHON LUC
Published: September 2007

Abstract:  Among the multiple autoantibodies identified in the serum of systemic sclerosis (SSc) patients, three are disease‐specific, mutually exclusive, and helpful to determine the prognosis: anticentromere antibodies, antitopoisomerase 1 antibodies (ATA), and anti‐RNA‐polymerase III antibodies. ATA can be identified through different techniques, including double immunodiffusion (DID) assay, enzyme‐linked immunosorbent assay (ELISA), or immunoblot. Although all of them are commonly used, none of them can be considered as the reference. Herein, we propose a brief description of the different methods available for the detection of ATA. All these studies revealed that ATA, determined by DID assay, ELISA, or immunoblot, are highly specific for SSc although the reported sensitivity is fickle. As we recently reported, patients with ATA had an almost similar phenotype without distinction between the methods of detection, ELISA, and immunoblot, and the use of these two techniques improves the sensitivity without diminishing the specificity. Thus, we may propose that a combination of the immunoblot using HEp‐2 cells antigens and ELISA could be used for the detection of ATA.
Reliability of Control Skin Tests with Common Antigens in Children Undergoing Tuberculin Skin Test
Authors: STEIN MICHAL , SELA‐RAZON BATIA , KLETER YESHAYAOU , SOMEKH ELI
Published: September 2007

Abstract:  The aim of this study was to determine the reliability of skin tests with common antigens as a measure of delayed‐type hypersensitivity response in children undergoing tuberculin skin test (TST). Children from developing countries underwent TST as well as skin tests with diphtheria–tetanus vaccine (DT) and candida antigens prior to heart surgery. We included 52 children (mean age: 7.16 years). Forty‐two (81%) and 20 of the 52 patients (38%) reacted to the DT and candida skin tests, respectively (P < 0.001 for the difference in response to these antigens). There was no difference in response to candida and DT antigens between patients with positive or negative TST. There was no difference between patients aged 6 years or older compared to younger patients in the response to DT or candida antigen. Skin tests with common antigens are associated with a high false‐negative rate and may not predict reliably a state of anergy.
A New Line Immunoassay for the Multiparametric Detection of Antiganglioside Autoantibodies in Patients with Autoimmune Peripheral Neuropathies
Authors: CONRAD KARSTEN , SCHNEIDER HAUKE , ZIEMSSEN TJALF , TALASKA THOMAS , REINHOLD DIRK , HUMBEL RENE‐LOUIS , ROGGENBUCK DIRK
Published: September 2007

Abstract:  A novel line immunoassay for the multiparametric detection of 11 antiganglioside autoantibodies (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, and GQ1b) was evaluated by comparing the reactivities in sera of 77 patients with suspected or definite autoimmune peripheral neuropathies (PNP), 60 blood donors, and 30 systemic lupus erythematodes (SLE) patients. At least one antiganglioside autoantibody was detectable in 97.4% of the patients with neuropathies compared to 12.2% in the control group. A broad spectrum of reactivities with more than two antiganglioside autoantibodies including all tested gangliosides except GD2 and GT1b was found in nearly one‐third of the patients with neuropathies whereas in the control group autoantibody profiles with more than two reactivities were observed in two SLE patients only. For the first time anti‐GM4 IgG and IgM antibodies were shown in PNP including Guillain–Barré syndrome (GBS), Miller–Fisher syndrome (MFS), and multifocal motor neuropathy (MMN). Different autoantibody profiles detectable by this multiparametric assay may help to diagnose different entities within the growing spectrum of autoimmune PNP.
Prevalence of Antinucleosome Antibodies by Enzyme‐Linked Immunosorbent Assays in Patients with Systemic Lupus Erythematosus and Other Autoimmune Systemic Diseases
Authors: PŮTOVÁ IVANA , DOSTAL C. , BECVAR R.
Published: September 2007

Abstract:  The objective was to report our experience with the detection of antinucleosome antibodies (anti‐Ncs Ab) in a series of systemic lupus erythematosus (SLE) patients, and to compare these results with those of antihistone and anti‐double‐stranded (ds) DNA antibodies. For this we selected 128 patients (106 females, 22 males, mean age 40 years) including 52 patients with SLE without organ involvement, 14 with lupus nephritis, 8 with neuropsychiatric lupus (NPSLE), 39 with systemic sclerosis (SSc), 15 with Sjögren syndrome (SS), and 51 healthy controls (38 females, 13 males, mean age 42 years). The sera were assayed for the levels of anti‐ds DNA (ELISA), antihistone (INNO LIA ANA Update), anti‐Ncs Ab (ELISA) and antinuclear antibodies (ANA‐indirect immunofluorescence (IIF) on Hep‐2 cells). The frequencies of positive anti‐Ncs Ab, anti‐ds DNA, and antihistone antibodies were in group of patients with SLE: 73%, 63%, and 54%, with SSc: 18%, 8%, 5%, and with SS: 3%, 3% and 0%, respectively. Patients with SLE have significantly increased levels of anti‐Ncs Ab in their sera compared to healthy controls, SSc patients, and patients with SS. The concentration of the anti‐Ncs Ab was 76 IU/mL in the SLE patients, 139 IU/mL in cases with lupus nephritis, 117 IU in NPSLE patients, 15 IU/mL in the SSc and 8 IU/mL in the healthy controls. All the three autoantibodies were present more frequently in cases with lupus and this correlation was significant in statistical means. Antinucleosome IgG antibodies seem to be a more sensitive marker of SLE than anti‐ds DNA.
Predictive Value of Antibodies to Citrullinated Peptides and Rheumatoid Factors in Anti‐TNF‐α Treated Patients
Authors: BOBBIO‐PALLAVICINI FRANCESCA , CAPORALI ROBERTO , ALPINI CLAUDIA , MORATTI REMIGIO , MONTECUCCO CARLOMAURIZIO
Published: September 2007

Abstract:  This article will focus on the relationship between serum levels of anti‐citrullinated peptide antibodies (anti‐CCP) or rheumatoid factor (RF) and clinical response to TNF‐α blockers in order to evaluate whether these antibodies may have a role as serological markers of response to therapy in rheumatoid arthritis (RA). The changes induced in anti‐CCP levels after TNF blocking therapy still remain a controversial issue even though a marked reduction following conventional DMARDs has been reported in early disease. On the other hand, a drop in RF levels during treatment has been reported by many authors. Decreased IgM RF levels seem to parallel clinical response suggesting that this antibody can also be regarded as a marker of response to treatment. Pre‐treatment RF positivity or negativity does not influence response to TNF‐α blocking therapy while high pre‐treatment levels of IgA RF seem to be associated with a poor response rate.
Determination of Oxidized Low‐Density Lipoproteins (ox‐LDL) versus ox‐LDL/β2GPI Complexes for the Assessment of Autoimmune‐Mediated Atherosclerosis
Authors: LOPEZ LUIS R. , BUCKNER TAMMY R. , HURLEY BETH L. , KOBAYASHI KAZUKO , MATSUURA EIJI
Published: September 2007

Abstract:  The immunolocalization of oxidized low‐density lipoproteins (ox‐LDL), β2‐glycoprotein I (β2GPI), CD4+/CD8+ immunoreactive lymphocytes, and immunoglobulins in atherosclerotic lesions strongly suggested an active participation of the immune system in atherogenesis. Oxidative stress leading to ox‐LDL production is thought to play a central role in both the initiation and progression of atherosclerosis. ox‐LDL is highly proinflammatory and chemotactic for macrophage/monocyte and immune cells. Enzyme‐linked immunosorbent assays (ELISAs) to measure circulating ox‐LDL have been developed and are being currently used to assess oxidative stress as risk factor or marker of atherosclerotic disease. ox‐LDL interacts with β2GPI and circulating ox‐LDL/β2GPI complexes have been demonstrated in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). It has been postulated that β2GPI binds ox‐LDL to neutralize its proinflammatory and proatherosclerotic effects. Because β2GPI is ubiquitous in plasma, its interaction with ox‐LDL may mask oxidized epitopes recognized by capture antibodies potentially interfering with immunoassays results. The measurement of ox‐LDL/β2GPI complexes may circumvent this interference representing a more physiological and accurate way of measuring ox‐LDL.
Multiplex Assays to Diagnose Celiac Disease
Authors: LOCHMAN IVO , MARTIS PETER , BURLINGAME RUFUS W. , LOCHMANOVÁ ALEXANDRA
Published: September 2007

Abstract:  Patients with celiac disease are sensitive to the gluten fractions of wheat. Symptoms include gastrointestinal problems and a failure to thrive in children, but may range from headaches to general malaise in adults. Thus, it is difficult to diagnose celiac disease by symptoms alone. The standard diagnostic criteria include the presence of the characteristic anti‐gliadin or anti‐tissue transglutaminase antibodies (anti‐tTG) in serum, flattened mucosa on intestinal biopsy, and improved symptoms on a gluten‐free diet. Because of the ease of use of the tTG enzyme‐linked immunosorbent assay (ELISA) compared to endomysial by indirect immunofluorescence assay, there has been much more screening for celiac disease in recent years. This increased screening showed that celiac disease was more prevalent than previously believed. We compared a new multiplex assay that includes a novel form of deamidated gliadin and recombinant human tTG as the antigens to other assays using standard antigens. In addition, the new assay detects the presence of selective IgA deficiency, which shows a 10‐fold increase in prevalence in patients with celiac disease compared to the general population. The combination of sensitivity and specificity of the new multiplex assay was equal or better than those for standard assays. Thus the performance, ease of use, and ability to measure three clinically important parameters in a single test make the new multiplex assay a viable alternative to standard assays in a clinical lab.
Could Serum Antibody to Poly(ADP‐Ribose) and/or Histone H1 Be Marker for Senile Dementia of Alzheimer Type?
Authors: KANAI YOSHIYUKI , AKATSU HIROYASU , IIZUKA HIDEKI , MORIMOTO CHIKAO
Published: September 2007

Abstract:  Poly(ADP‐ribosyl)ation has been focused on ischemic injury in the brain in relation to Alzheimer's disease (AD). We have measured IgG antibodies against poly adenosine diphosphate‐ribose (pADPR) as well as histone H1 (H1) in 26 patients with either AD or with senile dementia of Alzheimer type (SDAT), and found that 80.7% (21/26) were positive for anti‐pADPR IgG antibodies. Anti‐H1 IgG antibodies were less positive (57.6%) (15/26) than anti‐pADPR IgG antibodies, however, titers of both antibodies were well correlated (r= 0.768). Meanwhile, similar studies on 32 patients with systemic lupus erythematosus (SLE) who were positive for anti‐pADPR antibody showed poor correlation (r= 0.184) and the difference in the correlation was statistically significant (r < 0.01). It is worthy of remark that anti‐double‐stranded (ds) DNA antibody, which is the hallmark of SLE, was negative in all dementia patients. Together with the findings that major subclass in dementia is both IgG1 and IgG2 and that in SLE was IgG2, the mode of production of anti‐pADPR antibody in AD and SDAT is under different regulation mechanisms from that in SLE. Given the evidence that major target for ADP‐ribosylation is H1 molecule, the association between anti‐pADPR and anti‐H1 in AD/SDAT makes sense and supports the concept that modification of proteins renders them immunogenic. Whatever the regulation is, parallel assay of two antibodies above would be of use not only for monitoring the disease process but also as a prodrome for possible subsets of SDAT and AD.
Identification by Proteomic Tool of Atypical Anti‐Liver/Kidney Microsome Autoantibodies Targets in de Novo Autoimmune Hepatitis after Liver Transplantation
Authors: HUGUET STÉPHANIE , VINH JOELLE , JOHANET CATHERINE , SAMUEL DIDIER , GIGOU MICHÈLE , ZAMFIR OANA , DUCLOS‐VALLÉE JEAN‐CHARLES , BALLOT ERIC
Published: September 2007

Abstract: 
De novo autoimmune hepatitis (AIH) occurs after liver transplantation for nonautoimmune disorders. Autoantibodies so‐called atypical anti‐liver/kidney microsome antibodies (LKMA) with an unusual liver/kidney cytoplasmic staining as judged by indirect immunofluorescence, can be detected in some patients' sera. Few studies investigated their molecular targets, and the aim of this work was to identify the atypical anti‐LKMA targets by proteomic tool. This proteomic approach consisted of (a) two‐dimensional gel electrophoresis of cytosolic and microsomal proteins obtained by differential centrifugations of rat liver and rat kidney, followed by (b) two‐dimensional immunoblotting with sera of patients with de novo AIH (n= 8, including 2 with anti‐LKMA antibodies) and then (c) identifications of interest spots performed by ion trap mass spectrometry. By this way several proteins at 25 kDa were unambiguously identified: isoforms of carbonic anhydrase III, members of different glutathione S‐transferase (GST) families, and subunit β1 of proteasome. This is the first report of proteasome and carbonic anhydrase III as autoantigens in de novo AIH. These results could lead to a better diagnosis of this disease using identified autoantigens in diagnostic tests, and strengthen proteomic approach as a new way of autoantigens investigation.
Exploring cDNA Phage Display for Autoantibody Profiling in the Serum of Multiple Sclerosis Patients
Authors: GOVARTS C. , SOMERS K. , HUPPERTS R. , STINISSEN P. , SOMERS V.
Published: September 2007

Abstract:  We applied a cDNA phage display method called serological antigen selection (SAS) to identify immunogenic targets that evoke an autoantibody response in the serum of multiple sclerosis (MS) patients. This method involves the display of a cDNA expression library, in this study a MS brain library, on filamentous phage and subsequent selection using patient immunoglobulin G (IgG). To apply the SAS technology for autoantibodies in the serum of MS patients, an optimization was necessary to deplete cDNA products that encode IgG fragments derived from B cells present in the MS brain plaques. We describe a differential screening procedure in which positive selection rounds on MS serum and negative selection rounds on healthy control serum were alternated to optimize the selection procedure. As a result, a substantial decrease of IgG‐displaying phage clones was observed after each negative selection round, thereby preventing an overgrowth of IgG‐displaying phage clones. Our depletion strategy was therefore successful in preventing the enrichment of IgG‐displaying phage clones. This approach will facilitate the identification of possible MS‐related antigens.
Novel Biomarkers in Autoimmune Diseases
Authors: ORBACH HEDI , ZANDMAN‐GODDARD GISELE , AMITAL HOWARD , BARAK VIVIAN , SZEKANECZ ZOLTAN , SZUCS GABRIELLA , DANKO KATALIN , NAGY ENDRE , CSEPANY TUNDE , CARVALHO JOZELIO F. , DORIA ANDREA , SHOENFELD YEHUDA
Published: September 2007

Abstract:  The development of autoimmune diseases may be influenced by hormonal, immunomodulatory, and metabolic pathways. Prolactin (PRL), ferritin, vitamin D, and the tumor marker tissue polypeptide antigen (TPA) were measured in autoimmune diseases: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis (PM), dermatomyositis (DM), multiple sclerosis (MS), autoimmune thyroid diseases, and antiphospholipid syndrome. Hyperprolactinemia (HPRL) was detected in 24% of PM patients, in 21% of SLE patients, in 6.7% of MS patients, 6% of RA patients, and in 3% of SSc patients. Hyperferritinemia was detected in 23% of SLE patients, 15% of DM patients, 8% of MS patients, and 4% of RA patients. The patients had relatively low levels of 25 OH Vitamin D: the average results (mean ± SD) were between 9.3 ± 4.4 to 13.7 ± 7.1 ng/mL in the different diseases, while the 25 OH Vitamin D concentrations less than 20 ng/mL are regarded as deficient. TPA levels were in the same range of the controls, elevated only in SLE. HPRL, hyperferritinemia, hypovitaminosis D, and TPA levels did not correlate with SLE activity elevated levels of rheumatoid factor or anti‐CCP antibodies in RA. HPRL, hyperferritinemia, and hypovitaminosis D have different immunological implications in the pathogenesis of the autoimmune diseases. Preventive treatment with vitamin D or therapy for HPRL with dopamine agonists, may be considered in certain cases. Hyperferritinemia may be used as an acute‐phase reactant marker in autoimmune diseases mainly SLE. TPA may be used to indicate the tendency for malignancies.
Antinucleosome Antibodies and Systemic Lupus Erythematosus
Authors: DÜZGÜN NURŞEN , ŞAHIN MEHMET , GENÇ YASEMIN , TUTKAK HÜSEYIN
Published: September 2007

Abstract:  The aim of this study is to investigate the prevalence of antinucleosome antibody in systemic lupus erythematosus (SLE) and their association with disease activity and renal involvement. The study included 131 patients with SLE, 74 rheumatoid arthritis, 26 systemic sclerosis, and 50 healthy individuals. Antinucleosome antibody and anti‐dsDNA antibody were measured by an enzyme‐linked immunosorbent assay (ELISA). Antinuclear antibody was tested by immunofluorescence using HEp‐2 cells. Out of 131 SLE patients, 72 (54.9%) were seropositive for antinucleosome antibody, which was significantly higher than only 3 of 74 (4%) patients with rheumatoid arthritis (χ2= 52.82, P < 0.001); none of the patients with systemic sclerosis and 50 healthy individuals were seropositive. The sensitivity and specificity of antinucleosome antibodies in SLE were 83.6% and 70%, respectively. Fifty‐one (38.9%) of SLE patients had renal involvement. Among these patients, the rate of antinucleosome positivity and anti‐dsDNA were 74.5% and 78.4%, respectively. Antinucleosome antibodies were found to be 31.4% positive in SLE patients lacking anti‐dsDNA antibody. Antinucleosome antibodies significantly correlated with disease activity (r= 0.428, P < 0.001) and anti‐dsDNA (r= 0518, P < 0.001). The positivity of antinucleosome antibodies was significantly higher in patients with renal disease than the subjects without renal disease (χ2= 12.89, P < 0.001). The results of our study have revealed that in SLE patients, antinucleosome antibody could be a useful parameter for the assessment of disease activity or renal involvement.
Comparison of Three Multiplex Immunoassays for Detection of Antibodies to Extractable Nuclear Antibodies Using Clinically Defined Sera
Authors: COPPLE SUSAN S. , MARTINS THOMAS B. , MASTERSON CHARLIN , JOLY ERWANN , HILL HARRY R.
Published: September 2007

Abstract:  We set out to determine the agreement of three multiplex immunoassays for the detection of autoantibodies involved in connective tissue disease using clinically defined sera. Usefulness of the immunoassays will be defined by correlation to disease state. Using the immunoassays from Inova Diagnostics, Biomedical Diagnostics (BMD), and AtheNA, reactivity, to Smith (Sm), ribonucleic protein (RNP), SSA (Ro), SSB (La), Scl‐70, and dsDNA or chromatin, we tested 273 clinically defined sera consisting of 57 systemic lupus erythrematosus (SLE) sera, 69 rheumatoid arthritis (RA) sera, 47 sera defined as various other connective tissue diseases, and 100 normal donor sera. Samples were also tested for anti‐nuclear antibody (ANA) oN HEp‐2 cells by IFA for analysis of discrepant results. Inova, BMD, and AtheNA assays demonstrated 57%, 89%, and 80% concordance, respectively, in the 47 connective tissue disease sera. The BMD assay was the most sensitive in detecting Scl‐70. The immunoassays did not correlate well in the 57 SLE‐defined sera; however, each had a variety of antibodies positive for each serum. The AtheNA assay demonstrated the highest degree of nonspecificity. Inova, BMD, AtheNA, and the Inova ANA HEp‐2 IFA demonstrated 97%, 98%, 97%, and 99% specificity, respectively, using normal sera. Thus, all three assays showed a 97% or better negative predictive value. Positive correlation varied from 83% to 98%. Antibodies in SLE sera did not compare well among the three immunoassays. Significant variation in specificity and sensitivity due to individual characteristics of each assay was demonstrated, with the BMD assay showing the highest correlation with clinical diagnosis.
Biological and Clinical Relevance of Anti‐Prothrombin Antibodies
Authors: GHIRARDELLO ANNA , BIZZARO NICOLA , ZAMPIERI SANDRA , IACCARINO LUCA , BASSI NICOLA , TOZZOLI RENATO , RUFFATTI AMELIA , VILLALTA DANILO , TONUTTI ELIO , DORIA ANDREA
Published: September 2007

Abstract:  Anti‐prothrombin (anti‐PT) antibodies are recently identified antibodies directed toward a phospholipid‐binding protein (prothrombin), which deserve attention for the reported clinical and pathogenic relevance in antiphospholipid syndrome and systemic lupus erythematosus (SLE). We have recently carried out a longitudinal study on the predictive value of anti‐PT antibodies in SLE showing that they have a higher diagnostic accuracy for thrombosis than anti‐β2‐GPI and anticardiolipin antibodies, and, along with LAC activity, are the best predictors of thromboembolic events in SLE patients.
Retail-Price Drivers and Retailer Profits
Authors: Nijs Vincent R. , Srinivasan Shuba , Pauwels Koen
Published: September 2007

What are the drivers of retailer pricing tactics over time? Based on multivariate time-series analysis of two rich data sets, we quantify the relative importance of competitive retailer prices, pricing history, brand demand, wholesale prices, and retailer category-management considerations as drivers of retail prices. Interestingly, competitive retailer prices account for less than 10% of the over-time variation in retail prices. Instead, pricing history, wholesale price, and brand demand are the main drivers of retail-price variation over time. Moreover, the influence of these price drivers on retailer pricing tactics is linked to retailer category margin. We find that demand-based pricing and category-management considerations are associated with higher retailer margins. In contrast, dependence on pricing history and pricing based on store traffic considerations imply lower retailer margins.
Greedoid-Based Noncompensatory Inference
Authors: Yee Michael , Dahan Ely , Hauser John R. , Orlin James
Published: September 2007

Greedoid languages provide a basis to infer best-fitting noncompensatory decision rules from full-rank conjoint data or partial-rank data such as consider-then-rank, consider-only, or choice data. Potential decision rules include elimination by aspects, acceptance by aspects, lexicographic by features, and a mixed-rule lexicographic by aspects (LBA) that nests the other rules. We provide a dynamic program that makes estimation practical for a moderately large numbers of aspects.

We test greedoid methods with applications to SmartPhones (339 respondents, both full-rank and consider-then-rank data) and computers (201 respondents from Lenk et al. 1996). We compare LBA to two compensatory benchmarks: hierarchical Bayes ranked logit (HBRL) and LINMAP. For each benchmark, we consider an unconstrained model and a model constrained so that aspects are truly compensatory. For both data sets, LBA predicts (new task) holdouts at least as well as compensatory methods for the majority of the respondents. LBA’s relative predictive ability increases (ranks and choices) if the task is full rank rather than consider then rank. LBA’s relative predictive ability does not change if (1) we allow respondents to presort profiles, or (2) we increase the number of profiles in a consider-then-rank task from 16 to 32. We examine trade-offs between effort and accuracy for the type of task and the number of profiles.
The 2005 ISMS Practice Prize Competition—Special Section Introduction: The 2005 ISMS Practice Prize Competition
Authors: Lilien Gary L.
Published: September 2007

We report on the finalists from the 2005 Informs Society for Marketing Science (ISMS) Practice Prize Competition, representing the best examples of rigor plus relevance that our profession produces.
Practice Prize Report—Quantifying and Improving Promotion Effectiveness at CVS
Authors: Ailawadi Kusum L. , Harlam Bari A. , César Jacques , Trounce David
Published: September 2007

We quantified the net unit and profit impact of each promotion offered in 2003 by CVS, a leading U.S. drug retail chain, and analyzed the key drivers of variation in this net impact. We used this analysis to identify the least effective promotions and conducted a controlled field test to demonstrate the impact of eliminating them before chainwide implementation. Our key findings are as follows. First, approximately 45% of the gross lift from promotions is incremental for CVS. Further, for every unit of gross lift, 0.16 unit of some other product is purchased elsewhere in the store. Still, more than 50% of promotions are not profitable because the lower promotional margin is not sufficiently offset by incremental units. Second, there is substantial variation in net profit impact across categories. Our field test shows that eliminating promotions chainwide in 15 of the worst performing categories will decrease sales by about $7.8 million but will improve profit by approximately $52.6 million. This is very impressive given that CVS front store sales in 2003 were approximately $9 billion while the net profit impact of promotions was −$25.3 million.
Mapping the Bounds of Incoherence: How Far Can You Go and How Does It Affect Your Brand?
Authors: Kayande Ujwal , Roberts John H. , Lilien Gary L. , Fong Duncan K. H.
Published: September 2007

Consumers often have to evaluate products comprising a combination of attributes that is not expected by them, given their beliefs about how attributes normally co-vary in the product category. Such an attribute combination implies that the claimed level of a product attribute is then different from what the consumer might infer, given the level of another attribute, resulting in what we call product incoherence. We develop a model to calibrate the effect of incoherence on perceptions, uncertainty, preference, and ultimately purchase. Our model can allow managers to determine consumers’ acceptance for different positions in the multiattribute space, so they can optimize their product’s positioning. Our model implies that a product that combines positively valued attributes might increase some elements of preference for the product, but if those attributes occur in unexpected combinations, incoherence will also increase uncertainty which in turn might lower other elements of preference. The net risk-adjusted preference for a product in our model accommodates both the benefit from the expected attribute levels and the uncertainty associated with incoherence. We derive implications from the model and provide an empirical test that supports those implications.
Embedded Premium Promotion: Why It Works and How to Make It More Effective
Authors: Arora Neeraj , Henderson Ty
Published: September 2007

In this paper we define an embedded premium (EP) as an enhancement that involves a social cause added on to a product or service. We characterize EP as a sales promotion strategy and juxtapose it with traditional approaches, such as discounts and rebates. Across three experiments, using a nationwide Internet panel and employing stated measures and model-based inference, we find that at low denominations EP is more effective than an equivalent price discount. We describe how an EP’s social association may influence consumer choice quite differently than price promotions and, contrary to the asymmetric price promotion effect documented in the promotions literature, we find that EP benefits an unknown brand more than a known brand. Our hierarchical Bayes approach uncovers heterogeneity in EP effectiveness that can be explained by affinity toward the focal charity, personal motivations, and demographic markers. An identifiable segment of individuals prefer the “other” over “self,” suggesting possible EP optimization and segmentation strategies. Two such strategies, customization and coverage, are empirically tested, and the former is shown to be very effective. Our findings have broad implications for brand managers with regard to resource allocation and EP program return on investment (ROI), as well as important social welfare implications.
The Influence of Product Variety on Brand Perception and Choice
Authors: Berger Jonah , Draganska Michaela , Simonson Itamar
Published: September 2007

We propose that the variety a brand offers often serves as a quality cue and thus influences which brand consumers choose. Specifically, brands that offer a greater variety of options that appear compatible and require similar skills tend to be perceived as having greater category expertise or core competency in the category, which, in turn, enhances their perceived quality and purchase likelihood. Six studies support this proposition and demonstrate that compared to brands which offer fewer products, (a) brands which offer increased compatible variety are perceived as having higher quality; (b) this effect is mediated by product variety’s impact on perceived expertise; (c) the higher perceived quality produces a greater choice share of the higher variety brand, even among consumers who select options that multiple brands offer and (d) product variety also impacts post-experience perceptions of taste. The findings suggest that in addition to directly affecting brand choice share through influencing the fit with consumer preferences, product line length can also indirectly affect brand choice through influencing perceived brand quality.
Outcome of single-event multilevel surgery in untreated cerebral palsy in a developing country
Authors: Khan M. A.
Published: September 2007

In developed countries, children with cerebral palsy are treated from the time of diagnosis. This is usually not the case in developing countries where such patients often present at an age when it is traditionally believed that if walking has not already commenced, it is unlikely to. This study reports the outcome of the surgical treatment of 85 spastic diplegic patients at a mean of 8.5 years (5 to 12). All presented as untreated non-walkers and had achieved sitting balance by the age of five to six years. They underwent single-event multilevel surgery followed by physiotherapy and orthotic support. For outcome assessment, a modified functional walking scale was used at a mean of 3.5 years (2 to 5) post-operatively.

At all levels, static joint contractures had resolved almost completely. All patients improved and became walkers, 18 (21.2%) as exercise, 39 (45.9%) as household and 28 (33%) as community walkers.

This study shows that children with cerebral palsy who cannot walk and have not been treated can be helped by single-event multilevel surgery, provided that inclusion criteria are followed and a structural, supervised rehabilitation programme is in place.
Post-operative blood salvage with autologous retransfusion in primary total hip replacement
Authors: Smith L. K. , Williams D. H. , Langkamer V. G.
Published: September 2007

Clinical, haematological or economic benefits of post-operative blood salvage with autologous blood re-transfusion have yet to be clearly demonstrated for primary total hip replacement. We performed a prospective randomised study to analyse differences in postoperative haemoglobin levels and homologous blood requirements in two groups of patients undergoing primary total hip replacement.

A series of 158 patients was studied. In one group two vacuum drains were used and in the other the ABTrans autologous retransfusion system. A total of 58 patients (76%) in the re-transfusion group received autologous blood. There was no significant difference in the mean post-operative haemoglobin levels in the two groups. There were, however, significantly fewer patients with post-operative haemoglobin values less than 9.0 g/dl and significantly fewer patients who required transfusion of homologous blood in the re-transfusion group. There was also a small overall cost saving in this group.
Retrieval analyses of highly cross-linked polyethylene acetabular liners four and five years after implantation
Authors: Knahr K. , Pospischill M. , Köttig P. , Schneider W. , Plenk H.
Published: September 2007

Two Durasul highly crosslinked polyethylene liners were exchanged during revision surgery four and five years after implantation, respectively. The retrieved liners were evaluated macroscopically and surface analysis was performed using optical and electron microscopy. A sample of each liner was used to determine the oxidation of the material by Fourier transform infrared spectroscopy. Samples of the capsule were examined histologically.

The annual wear rate was found to be 0.010 and 0.015 mm/year, respectively. Surface analysis showed very little loss of material caused by wear. Histological evaluation revealed a continuous neosynovial lining with single multinucleated foreign-body giant cells. Our findings showed no unexpected patterns of wear on the articulating surfaces up to five years after implantation and no obvious failure of material.
Congenital talipes equinovarus
Authors: Siapkara A. , Duncan R.
Published: September 2007

Talipes equinovarus is one of the more common congenital abnormalities affecting the lower limb and can be challenging to manage. This review provides a comprehensive update on idiopathic congenital talipes equinovarus with emphasis on the initial treatment. Current management is moving away from operative towards a more conservative treatment using the Ponseti regime. The long-term results of surgical correction and the recent results of conservative treatment will be discussed.
Treatment of benign bone tumours using external fixation
Authors: Tsuchiya H. , Morsy A. F. , Matsubara H. , Watanabe K. , Abdel-Wanis M. E. , Tomita K.
Published: September 2007

We present a retrospective study of patients suffering from a variety of benign tumours in whom external fixators were used to treat deformity and limb-length discrepancy, and for the reconstruction of bone defects. A total of 43 limbs in 31 patients (12 male and 19 female) with a mean age of 14 years (2 to 54) were treated.

The diagnosis was Ollier’s disease in 12 limbs, fibrous dysplasia in 11, osteochondroma in eight, giant cell tumour in five, osteofibrous dysplasia in five and non-ossifying fibroma in two. The lesions were treated in the tibia in 19 limbs, in the femur in 16, and in the forearm in eight. The Ilizarov frame was used in 25 limbs, the Taylor Spatial Frame in seven, the Orthofix fixator in six, the Monotube in four and the Heidelberg fixator in one. The mean follow-up was 72 months (22 to 221).

The mean external fixation period was 168 days (71 to 352). The mean external fixation index was 42 days/cm (22.2 to 102.0) in the 22 patients who required limb lengthening. The mean correction angle for those with angular deformity was 23° (7° to 45°).

At final follow-up all patients had returned to normal activities. Four patients required a second operation for recurrent deformity of further limb lengthening. Local recurrence occurred in one patient, requiring further surgery.
Iliopsoas impingement after total hip replacement
Authors: Dora C. , Houweling M. , Koch P. , Sierra R. J.
Published: September 2007

We have reviewed a group of patients with iliopsoas impingement after total hip replacement with radiological evidence of a well-fixed malpositioned or oversized acetabular component. A consecutive series of 29 patients (30 hips) was assessed. All had undergone a trial of conservative management with no improvement in their symptoms. Eight patients (eight hips) preferred continued conservative management (group 1), and 22 hips had either an iliopsoas tenotomy (group 2) or revision of the acetabular component and debridement of the tendon (group 3), based on clinical and radiological findings. Patients were followed clinically for at least two years, and 19 of the 22 patients (86.4%) who had surgery were contacted by phone at a mean of 7.8 years (5 to 9) post-operatively. Conservative management failed in all eight hips. At the final follow-up, operative treatment resulted in relief of pain in 18 of 22 hips (81.8%), with one hip in group 2 and three in group 3 with continuing symptoms. The Harris Hip Score was significantly better in the combined groups 2 and 3 than in group 1. There was a significant rate of complications in group 3. This group initially had better functional scores, but at final follow-up these were no different from those in group 2.

Tenotomy of the iliopsoas and revision of the acetabular component are both successful surgical options. Iliopsoas tenotomy provided the same functional results as revision of the acetabular component and avoided the risks of the latter procedure.
A conservative approach is feasible in unexplained pain after knee replacement
Authors: Elson D. W. , Brenkel I. J.
Published: September 2007

Pain is the main indication for performing total knee replacement (TKR). In most patients after TKR there is an improvement, but a few continue to have pain. Generally, the cause of the pain can be addressed when it is identified. However, unexplained pain can be more difficult to manage because revision surgery is likely to be unrewarding in this group. In our study of 622 cemented TKRs in 512 patients with a mean age of 69 years (23 to 90) treated between January 1995 and August 1998, we identified 24 patients (knees) with unexplained pain at six months. This group was followed for five years (data was unavailable for 18 knees) and ten patients (55.5%) went on to show an improvement without intervention.

In the case of unexplained pain, management decisions must be carefully considered, but reassurance can be offered to patients that the pain will improve in more than half with time.
Privity of Estate and the Enforcement of Real Covenants
Authors: Goulding Simon
Published: September 2007

The inability to enforce positive covenants against successors in title of freehold property in England, no matter how beneficial or reasonable, has been a persistent and seemingly intractable problem. But a comparison with the position taken in the jurisdictions of the US on this point reveals a marked difference in approach, where enforcement of covenants against freeholders is no more remarkable than it is against leaseholders. Curiously though, in both England and the US the same basis for the law is stated to be privity of estate. This article examines the meaning of privity of estate in both legal traditions to identify the disparity of definition and then focuses on whether the restricted meaning espoused by English law has been static and consistent. The conclusion is that it was English law which adopted a narrower view in the first half of the nineteenth century from a previous one more consistent with that of the US. Perhaps inevitably this led to the landmark case of Tulk v Moxhay which, of course, only provided a partial solution to the problem.
The Effect of a Finding That Legislation is Unconstitutional: The Approach of the Irish Supreme Court
Authors: O'Neill Ailbhe
Published: September 2007

A number of common law jurisdictions permit the judiciary to strike down legislation which is inconsistent with that legal system's constitution. The Irish Constitution makes specific provision for this in Article 34.3.2°. The power to declare legislation invalid gives rise to a number of interesting questions concerning the temporal effect of such decisions. In Ireland, the courts have consistently adopted an approach whereby incompatible legislation which postdates the 1937 Constitution is deemed to have been void ab initio. Incompatible legislation originally passed by the British Parliament before 1937 is deemed not to have survived in Irish law from the date of the adoption of the Constitution. This gives rise to interesting issues surrounding the effect of past legal determinations which were based on such legislation. This problematic aspect of constitutional interpretation was considered at length by the Irish Supreme Court in the case of A v The Governor of Arbour Hill Prison (the ‘ A case’) in July 2006. This article explains the approach taken by the Irish courts to this aspect of constitutional interpretation and analyses the way in which the problem of legal effect was approached by the Supreme Court in the A case.
The Tyranny of Words: Patent Claim Construction in the UK and US
Authors: Fisher Matthew
Published: September 2007

The creation of property rights in abstract concepts, such as invention, is a conceptually difficult process, a process made harder in the context of the patent right by the multifaceted nature of the chosen definitional medium: words. Words are familiar to us; we use them every day and appear to communicate with ease. But words are inherently tricky things, layered with nuance and meaning. Our familiarity with words breeds complacency for we feel we instinctively ‘know’ what they denote and therefore expect others to use them in the same manner to convey the same meaning. In the majority of cases this is unproblematic, but with patents—entities given boundary and form by the words used to describe their subject-matter—the repercussions of mis-communication are acute. This article examines the problem of conveying property's boundaries by words alone and considers the mechanisms used, and problems faced, by the courts in both the UK and the US, two systems (as George Bernard Shaw did not say) divided by more than a common language, when defining and interpreting property in invention.
Analysis of the Ductile-to-Brittle Transition Temperature Shift in a Commercial Power Plant With High Nickel Containing Weld Material
Authors: Efsing Pål , Jansson Christer , Mager Tom , Embring Göran
Published: September 2007

Plant specific surveillance programs that ideally include all relevant materials and materials combinations that are subjected to neutron irradiation during operation address the degradation due to irradiation of the reactor pressure vessel material for nuclear electric power plants. Plant specific surveillance programs are not unique to the two power plants treated in this study. The current Swedish regulatory system does, however, call for a fairly rigid approach within the surveillance program. In the Swedish case, this means that there is a plant specific predetermined inspection∕test program that has to be followed in order to verify the operability of the power plant and also to verify the operational limits with respect to pressure∕temperature effects on a repetitive basis. The two pressurized water reactor plants Ringhals 3 and 4 have in common that the weld metal used for the butt welds of the reactor pressure vessel is a high nickel type material, above the current limits of the NUREG Reg. Guide 1.99, rev. 2. In the original state, the high nickel content provides excellent fracture toughness in the unirradiated material condition and a low ductile-to-brittle transformation temperature (DBTT). It has, however, been highlighted in several studies that high nickel materials exhibit a very large DBTT shift as a consequence of irradiation, and also that the precipitates that form during the irradiation are not as easily controlled during a heat treatment to remove the irradiation damage as are the copper rich clusters. This paper will present the current state of the art regarding these effects as observed in the weld metal specimens. The paper will present the results from the Charpy V notched and fracture mechanics specimen test encapsulated in the Ringhals Units 3 and 4 surveillance programs. The results from the Ringhals Units 3 and 4 surveillance programs show that there is a need for corrective action to be taken in order to ensure 60 y of operability for the two power plants.
Hypothalamic and pituitary development: novel insights into the aetiology
Authors: Kelberman Daniel , Dattani Mehul Tulsidas
Published: September 2007

The anterior pituitary gland is a central regulator of growth, reproduction and homeostasis, and is the end-product of a carefully orchestrated pattern of expression of signalling molecules and transcription factors leading to the development of this complex organ secreting six hormones from five different cell types. Naturally occurring and transgenic murine models have demonstrated a role for many of these molecules in the aetiology of combined pituitary hormone deficiency (CPHD). These include the transcription factors HESX1, PROP1, POU1F1, LHX3, LHX4, TBX19, SOX2 and SOX3. The expression pattern of these transcription factors dictates the phenotype that results when the gene encoding the relevant transcription factor is mutated. The highly variable phenotype may consist of isolated hypopituitarism, or more complex disorders such as septo-optic dysplasia and holoprosencephaly. Since mutations in any one transcription factor are uncommon, and since the overall incidence of mutations in known transcription factors is low in patients with CPHD, it is clear that many genes remain to be identified, and the characterization of these will further elucidate the pathogenesis of these complex conditions and also shed light on normal pituitary development.
Pharmacogenomics and pharmacoproteomics in the evaluation and management of short stature
Authors: Rosenfeld Ron G
Published: September 2007

It has long been recognized that growth failure encompasses a diverse spectrum of underlying pathophysiological processes, a characteristic that has significantly impacted both the diagnosis and management of growth disorders. This problem is exacerbated by inherent difficulty in distinguishing the borders between the ‘normal range’ for stature and defined abnormal growth. Evaluation of GH secretion has proven problematic, both diagnostically and prognostically, except in cases of unequivocal GH deficiency. Measurement of serum concentrations of IGF-I, IGFBP-3, and ALS have proven useful in the assessment of GH responsiveness and have contributed to the concept of primary and secondary ‘IGF deficiency’. Nevertheless, there is great need for biochemical and/or molecular biomarkers that could: i) predict short- and long-term responsiveness to various therapeutic modalities, such as GH and IGF-I, and ii) predict potential risk for adverse effects of therapy. Candidate proteins and genes identified to date, and worthy of further evaluation, include IGF-I, IGF-I receptor, GH receptor and its variants (such as exon 3-deleted GHR), STAT5b and short stature homeobox. Proteomic analysis of serum samples pre- and post-treatment and correlation with clinical responsiveness should provide additional candidate biomarkers. Molecular studies to consider include: i) sequencing and mutation analysis of known genetic components of the GH–IGF axis; ii) evaluation of single nucleotide polymorphisms of candidate genes; and iii) identification of new candidate genes. It is proposed that the major target population to study is that of children currently labeled as idiopathic short stature (ISS). These children can be divided into those with: i) primary IGFD, where the focus should be on genes related to GHR, GHR signaling, and IGF-I gene expression, or ii) no IGFD (i.e. ‘true ISS’), where the focus should be on genes related to IGFR, IGF signaling and epiphyseal growth.