bluuebunny/crossref_metadata_2025 huggingface dataset:
Is economic value added more associated with stock return than accounting earnings? The UK evidence
Authors: Ismail Ahmad
Published: January 2007

Purpose

The paper seeks to examine the claim of EVA® advocates of its superiority as a financial metric compared with other measures.

Design/methodology/approach

The paper uses a sample of 2,252 firm‐year observations from the UK market and applies panel data regressions to test the relative information content of EVA and other accounting measures and the incremental information content of EVA components in explaining stock return.

Findings

It is found that net operating profit after tax and net income outperform EVA and residual income in explaining stock return; it was also found that accruals and operating cash flow have significant incremental information content, while the accounting adjustments of EVA proponents have significantly less contribution in explaining stock return. Yet the paper concludes that other variables must be considered in order to capture the unexplained variation in stock return models.

Research limitations/implications

Future research should include US and UK data in the same sample and examine whether the conclusions are maintained.

Originality/value

For a set of cross‐sectional time series data, ordinary least square (OLS) regressions produce biased results and inaccurate estimates of the parameters coefficients; however, this paper applies panel data regressions.
The “Strategic States Model”: strategies for business growth
Authors: Pehrsson Anders
Published: January 2007

Purpose

The purpose is to show that it is necessary for a company to choose a business strategy that relies on a thorough understanding of the company setting.

Design/methodology/approach

The Strategic States Model is presented and illustrated by the Ericsson case. Advices on application of the model are presented.

Findings

The case shows that a search for an optimum business strategy means competitiveness.

Practical implications

In applying the Strategic States Model, management would be advised to formulate business strategy step‐by‐step.

Originality/value

The article turns theoretical research into advices that are valuable for companies when they choose business strategies. The case shows that practical company situations can be generalized in accordance with strategy models.
Variation in day‐case nasal surgery – why cannot we improve our day‐case rates?
Authors: Hopkins C. , Browne J. , Slack R. , Brown P.
Published: February 2007

Objectives:  The NHS plan states that 75% of all elective operations should be performed as day‐cases. We set out to evaluate day surgery rates in sinonasal surgery and to identify factors limiting current practice.

Study Design and Setting:  Prospective multicentre cohort study.

Participants:  3128 patients undergoing sinonasal surgery during 2000 and 2001.

Outcome Measures:  Same day discharge, complication and readmission rates.

Results:  There is potential selection bias due to the non‐random selection of NHS Trusts and patients in this study. However, as results are similar to Hospital Episode Statistics data such bias is probably small. Only 15.5% of all procedures are performed as day surgery. We are achieving day‐case rates of 18, 20 and 6% for nasal polypectomy, intranasal antrostomy and extensive FESS respectively, compared with recently published targets of 90%, 80% and 50%. Factors significantly associated with overnight admission were use of packs, extensive surgery, excess post‐operative bleeding and high ASA grade. There was considerable unexplained variation in day‐case rates and the use of packs between different surgeons. A third of consultants pack all patients post‐operatively. More than 51% of consultants admit all patients, while 5% discharge all patients on the day of surgery. There were no excess adverse events or readmissions amongst the day surgery patients. However, only 17% of in‐patients would have liked to be discharged on the day of surgery. Both patient and surgeon must overcome resistance to day case surgery before targets can be reached.

Conclusions:  Strategies for improving day‐case rates in sinonasal surgery.

All ASA grade 1 and 2 patients could be considered for day‐case surgery, but particularly those with less extensive disease on radiography, and those planned to undergo less extensive procedures. Excess peri‐operative bleeding was reported in 6% of patients. There must therefore be provision for overnight admission if required. Greater utilisation of day‐case units, selective use of packs, and earlier removal may increase the proportion of patients managed as day‐cases. There remains considerable variation in practice at both consultant and trust levels. Units should continue to audit their own figures and compare them against national rates in order to reduce nationwide variation in practice.
Testing the gravity hypothesis of sexual size dimorphism: are small males faster climbers?
Authors: BRANDT YONI , ANDRADE MAYDIANNE C. B.
Published: January 2007

Moya‐Laraño et al. (2002; Evolution 56, 420–425) showed that female‐biased sexual size dimorphism is more pronounced in tree‐dwelling spider species than in species inhabiting lower‐lying substrates. They proposed the Gravity Hypothesis for sexual size dimorphism: small size should be advantageous for males in habitats where successful mate searching requires climbing, because mass‐specific power and hence the speed of climbing against gravity, must decrease with increasing size.

Their biomechanical model is based on a false premise, that the cross‐sectional area of a muscle determines its power output. In fact, muscle power is proportional to muscle volume, and hence mass‐specific power should be independent of size. We therefore predict, contrary to the Gravity Hypothesis, that climbing speed should be independent of body size.

We tested these contrasting predictions using adult male Western black widow spiders Latrodectus hesperus, a species in which males span a broad range of sizes.

In accordance with our prediction, and contrary to the Gravity Hypothesis, we found no relationship between vertical climbing speed and any of a series of size measures, whereas on a horizontal surface, speed was positively related to size.

Our results, as well as the error we exposed in the biomechanical model underlying the Gravity Hypothesis, indicate that selection for vertical climbing speed in males cannot account for patterns of sexual size dimorphism in spiders.
Scaling of insect metabolic rate is inconsistent with the nutrient supply network model
Authors: CHOWN S. L. , MARAIS E. , TERBLANCHE J. S. , KLOK C. J. , LIGHTON J. R. B. , BLACKBURN T. M.
Published: January 2007

The nutrient supply network model of the metabolic theory of ecology predicts that metabolic rate scales as mass0·75 at all hierarchical levels.

An alternative, cell size, model suggests that the scaling of metabolic rate is a by‐product of the way in which body size changes, by cell size or number, or some combination thereof. It predicts a scaling exponent of mass0·75 at the widest interspecific level, but values of mass0·67−1·0 for lower taxonomic groups or within species.

Here these predictions are tested in insects using 391 species for the interspecific analysis, and the size‐polymorphic workers of eight ant species at the intraspecific level. In the latter, the contribution of ommatidium size and number to variation in body length, which is closely related to eye size, is used to assess the relative contributions of changes in cell size and number to variation in body size.

Before controlling for phylogeny, metabolic rate scaled interspecifically as mass0·82. Following phylogenetic correction, metabolic rate scaled as mass0·75.

By contrast, the intraspecific scaling exponents varied from 0·67 to 1·0. Moreover, in the species where metabolic rate scaled as mass1·0, cell size did not contribute significantly to models of body size variation, only cell number was significant. Where the scaling exponent was < 1·0, cell size played an increasingly important role in accounting for size variation.

Data for one of the largest groups of organisms on earth are therefore inconsistent with the nutrient supply network model, but provide support for the cell size alternative.
Percutaneous liver biopsy in adult haemophiliacs with hepatitis C virus: safety of outpatient procedure and impact of human immunodeficiency virus coinfection on the spectrum of liver disease
Authors: STERLING R. K. , LYONS C. D. , STRAVITZ R. T. , LUKETIC V. A. , SANYAL A. J. , CARR M. E. , SMITH T. J. , HACKNEY M. H. , CONTOS M. J. , MILLS S. A. , KUHN J. G. , NOLTE M. E. , SHIFFMAN M. L.
Published: January 2007

Summary. Both HCV and HIV are common in haemophiliacs previously treated with non‐viral‐inactivated clotting factor concentrates. Because of increased bleeding risks, little data are available on the safety of percutaneous outpatient liver biopsy (LBx) and impact of HIV coinfection in this population. This study aims at reporting our experience with percutaneous LBx in a cohort of haemophiliacs infected with HCV and describe the spectrum of disease and impact of HIV coinfection. A retrospective review of consecutive patients with haemophilia and HCV who underwent percutaneous LBx was performed. All patients were positive for HCV RNA by commercial assay and received factor concentrate prior to biopsy. A total of 29 male patients (mean age 36, 24 haemophilia A, five haemophilia B, and 44% coinfected with HIV) underwent successful outpatient percutaneous LBx without bleeding complication. Histologic activity index was 6.44 with advanced fibrosis (bridging fibrosis/cirrhosis) in 31%. When patients were stratified by HIV positive (n = 13) vs. HIV negative (n = 16), coinfected patients had higher fibrosis scores and higher proportion advanced fibrosis (54% vs. 12%;P = 0.0167) with no differences in age, demographic or other laboratory parameters. Multivariate logistic regression found that HIV positivity was independently associated with advanced fibrosis (OR = 3.7; 95% CI: 1.17–11.8;P = 0.026). Outpatient percutaneous LBx can be safely performed in patients with haemophilia. Despite similar age, HIV coinfection was an independent predictor of advanced fibrosis. These data support the hypothesis that HIV accelerates fibrosis progression in those coinfected with HCV and highlights the importance of liver histology in this population.
CD4+ CD8+ T cells in young and elderly humans. Comment on Macchia I, Gauduin MC, Kaur A, Johnson RP. Expression of CD8α identifies a distinct subset of effector memory CD4+ T lymphocytes. Immunology 2006; 119:232–42
Authors: Herndler‐Brandstetter Dietmar , Schwanninger Angelika , Grubeck‐Loebenstein Beatrix
Published: February 2007

Peripheral CD4+ CD8+ T cells have been described in animals as well as in humans. Two distinct populations can be distinguished, namely CD4lo CD8hi and CD4hi CD8lo T cells. We demonstrate here that the increase in the number of peripheral CD4+ CD8+ T cells in the elderly is the result of an increase of the CD4lo CD8hi T‐cell population. While the phenotype of CD4lo CD8hi and CD4hi CD8lo T cells was very similar in young persons, CD4hi CD8lo, T cells from elderly subjects expressed a more differentiated phenotype and produced less interleukin‐2 compared to CD4lo CD8hi T cells. In conclusion, our results suggest that aging leads to a phenotypic and functional difference between CD4+ CD8+ T‐cell subsets. It may therefore be of relevance to distinguish between these subsets before assessing their functional significance in elderly humans.
Dental enamel defects in children with coeliac disease
Authors: WIERINK CLAAR D. , VAN DIERMEN DENISE E. , AARTMAN IRENE H. A. , HEYMANS HUGO S. A.
Published: February 2007

Objective.  The aim of this study was to investigate whether Dutch children with proven coeliac disease show specific dental enamel defects, and to asses whether children with the same gastrointestinal complaints, but proved no‐coeliac disease, lack these specific dental enamel defects.

Materials and methods.  Eighty‐one children (53 coeliac patients and 28 control subjects) were examined during the period 2003–2004 in the Oral Surgery Outpatient Clinic of the Academic Medical Centre in Amsterdam.

Result.  Twenty‐nine (55%) coeliac patients had enamel defects against 5 (18%) control subjects. In the coeliac disease group, the enamel defects were diagnosed as specific in 20 (38%) children, compared with 1 (4%) in the control group. Statistical analysis showed significantly more specific enamel defects in children with coeliac disease than in children in the control group (χ2 = 12.62, d.f. = 2, P = 0.002).

Conclusion.  This study showed significantly more specific enamel defects in Dutch children with coeliac disease as compared with children in the control group. Dentists could play an important role in recognizing patients with coeliac disease.
Prevalence of fractures in women with intellectual disabilities: a chart review
Authors: Schrager S. , Kloss C. , Ju A. W.
Published: January 2007

Background  Numerous studies have demonstrated high rates of osteoporosis and fractures in women with intellectual disabilities (IDs). All of the studies use either institutionalized women or women in the community recruited at adult day‐care centres or specialty clinics. We examined the prevalence of fractures in women with IDs who attend a primary care clinic, and assessed osteoporosis‐prevention/intervention activities.

Methods  This was a chart review study. Charts were identified of women with an ICD‐9 diagnosis code for ID, Down syndrome or developmental disabilities. All charts reviewed were patients of one of 13 family medicine clinics affiliated with Department of Family Medicine, the University of Wisconsin.

Results  A total of 93 charts were reviewed. More than 32% (30/93) of the charts contained a history of an adult‐onset fracture. Increasing age, being postmenopausal and taking anticonvulsant medications were significantly associated with having a fracture. The average age of first fracture was 41.7 years. Of the women with a fracture, 35.5% were placed on a medication to maintain bone density, 67.7% received a recommendation for a calcium supplement, and 38.7% obtained a bone density test.

Discussion  The prevalence of fractures in women with IDs attending a family medicine clinic was very high, and fractures occurred at young ages. Primary care providers need to consider women with IDs at a high risk for fractures and begin preventive counselling in young women.
Language comprehension in boys with fragile X syndrome and boys with Down syndrome
Authors: Price J. , Roberts J. , Vandergrift N. , Martin G.
Published: January 2007

Background Fragile X syndrome (FXS) is the most common known inherited cause of intellectual disability, yet very few studies have explored the language comprehension skills of children with FXS. We examined the receptive vocabulary, grammatical morphology and syntax skills of boys with FXS (who were additionally classified as having autism, autism spectrum, or no autism) and compared them to boys with Down syndrome (DS) and typically developing (TD) boys at similar non‐verbal developmental levels.

Methods The Vocabulary, Grammatical Morphology, and Elaborated Phrases and Sentences subtests of the Test for Auditory Comprehension of Language – 3rd Edition (TACL‐3) were administered annually up to three times to assess the language comprehension skills of 35 boys with FXS without autism, 24 boys with FXS with autism spectrum, 19 boys with FXS with autism, 45 boys with DS and 40 TD boys at similar non‐verbal cognitive levels.

Results After controlling for non‐verbal cognition and maternal education levels, we found that the three groups of boys with FXS did not differ from each other but scored lower than the TD boys in language comprehension. The boys with DS scored lower in language comprehension than boys with FXS without autism and TD boys. For all of the groups, scores for receptive vocabulary, grammatical morphology and syntax did not differ.

Conclusions Boys with FXS and boys with DS differed in receptive language levels, demonstrating unique language profiles for each syndrome. Language comprehension appears to be an important area to target in assessment and intervention for both populations.
A neuropsychological assessment of frontal cognitive functions in Prader–Willi syndrome
Authors: Jauregi J. , Arias C. , Vegas O. , Alén F. , Martinez S. , Copet P. , Thuilleaux D.
Published: January 2007

Background  Prader–Willi syndrome (PWS) is associated with a characteristic behavioural phenotype whose main features are, alongside compulsive hyperphagia, deficits in social behaviour: social withdrawal, temper tantrums, perseverative speech and behaviour, mental rigidity, stereotyped behaviour, impulsiveness, etc. Similar symptoms may also be found in autistic spectrum disorders and lesional pathologies of the frontal lobe. In both cases, such symptoms have been related to dysfunctions in frontal cognitive processes such as attention, working memory and executive functions. This study uses standardized neuropsychological instruments to analyse the degree to which these processes are affected in PWS.

Methods  The sample comprised 16 individuals with a genetically confirmed PWS diagnosis. Subjects’ IQ (Wechsler Adult Intelligence Scale), academic level, laterality and body mass index (BMI) were calculated. Attention, memory and executive functions were analysed using standard, widely employed neuropsychological tests. We compared the results of the sample group with the general population. Correlation analyses were carried out with IQ, academic level and BMI.

Results  In all the neuropsychological measures focusing on attention, executive functions and visuoperceptual organization, the study sample scored significantly lower than the normative reference population. The scores of the tests used for measuring immediate memory were also significantly lower when trials required sequential processing, although not when they required simultaneous processing. In the memorization of a list of words, subjects showed an initial deficit which disappeared with repetition, enabling them to obtain scores similar to the reference population. No significant correlations were found with BMI, and a higher IQ or academic level did not improve scores in the majority of tests.

Conclusions  The study shows a deficit in elementary frontal cognitive processes in PWS patients. This deficit may be involved in the social behaviour disorders that characterize such patients, as described in other development or frontal syndrome pathologies. However, we cannot affirm that the deficits found are specific to PWS; they could also occur in other causes of intellectual disability. Although in the study sample IQ did not correlate with frontal deficits, further research is needed to establish whether the neuropsychological alterations described form part of a cognitive phenotype for PWS. We believe that our understanding of the social behaviours typical of PWS may be improved by taking into consideration the cognitive functioning models of the prefrontal lobe, particularly those applied to pervasive developmental disorders.
Policy, service pathways and mortality: a 10‐year longitudinal study of people with profound intellectual and multiple disabilities
Authors: Hogg J. , Juhlberg K. , Lambe L.
Published: January 2007

Background One hundred and forty‐two children and adults with profound intellectual and multiple disabilities were identified in 1993 in a single Scottish region on whom detailed information was collected via a postal questionnaire survey.

Methods They were followed up in 2003. The time spanned represented a period of significant policy change in which community care and inclusive policies were implemented.

Results Of the original population of 142, 30 (21.1%) had died in the intervening period and two had left the area, allowing follow‐up information to be collected on 110 individuals. While in line with policy, all those living in hospital and hostels in 1993 had been relocated by 2003 to community settings, a substantial proportion had moved into other forms of congregate care, notably nursing homes. Overall, the proportion in congregate care increased from 38% in 1993 to 43% in 2003. The second principal providers were family carers, with the proportion of those living at home also increasing from 33% to 40%. Provision in group houses increased from 6.3% to 15.5%. Day service provision remained based on a traditional centre‐based model. The principal cause of death was respiratory disease. Survivors in 2003 were in 1993 more competent in personal self‐help and motor abilities and were less likely to have epilepsy.

Conclusions The findings are considered with respect to the extent to which they realize policy aspirations.
A preliminary study of the validity of memory tests recommended by the Working Group for individuals with moderate to severe intellectual disability
Authors: Pyo G. , Kripakaran K. , Curtis K. , Curtis R. , Markwell S.
Published: January 2007

Background  Normal aging and Dementia of Alzheimer’s Type (DAT) among higher functioning individuals with intellectual disability (ID) have been relatively well studied using a variety of cognitive tests. However, cognitive studies for lower functioning individuals with ID are scarce in the literature. The Working Group recommended the Test Battery for the Diagnosis of Dementia in Individuals with various level of ID. Few studies have investigated whether the Test Battery is useful to study dementia among individuals with moderate to severe ID. The purpose of this study is to investigate whether the memory subtests of the Test Battery are useful for measuring memory function and studying DAT in individuals with moderate to severe ID.

Methods  We compared performances on the memory subtests in the Test Battery between 31 normal controls and 13 DAT patients with moderate to severe ID. Performance on the Picture Recognition Test was also compared between five normal controls and five DAT patients. This test was designed by our team to measure memory functions of individuals with moderate to severe ID.

Results  Among the memory subtests of the Test Battery, the Autobiographical Memory and the Orientation were found to be useful for studying normal and abnormal aging among individuals with moderate to severe ID. Preliminary data for the Picture Recognition Test demonstrated that these individuals properly responded to this test and the majority of DAT patients could be differentiated from the normal controls based on their performance.

Conclusions  Further studies are necessary to improve usefulness of the memory subtests of the Test Battery for lower functioning individuals with ID. While the results suggest that the Picture Recognition Test may be more effective in discriminating individuals with DAT, given the very small sample sizes, a study with larger sample sizes should be undertaken to validate these findings.
Developing health indicators for people with intellectual disabilities. The method of the Pomona project
Authors: Van Schrojenstein Lantman‐de Valk H. , Linehan C. , Kerr M. , Noonan‐Walsh P.
Published: January 2007

Aim  Recently, attention has focused on the health inequalities experienced by people with intellectual disabilities (ID) when compared with the general population. To inform policies aimed at equalizing health opportunities, comparable evidence is needed about the aspects of their health that may be amenable to intervention.

Method  Applying the framework of the European Community Health Indicators (ECHI) for the general population, the Pomona group developed a set of health indicators reflecting aspects of the health of people with ID: socio‐demographic data, health status, health determinants and health systems.

Results  This paper documents the procedures that partners carried out in 13 European countries. The process comprised a search for evidence in published literature; consultation with advocates, family members and health professionals; and analyses of national and international databases. Indicators were selected if they were appraised as important, useful, measurable and if resulting data would enable comparisons between the health of people with ID and that of the general population.

Conclusion  The thus developed indicator set that is aligned with ECHI will permit investigators to compare key aspects of health of people with ID with those of people in the general population within Europe. The final set of 18 indicators will be applied in the Pomona 2 project (2005–08) to gather information about the health of samples of adults in 14 participating European countries.
Eustasy and sea water Sr composition: application to high‐resolution Sr‐isotope stratigraphy of Miocene shallow‐water carbonates
Authors: KROEGER K.F. , REUTER M. , FORST M.H. , BREISIG S. , HARTMANN G. , BRACHERT T.C.
Published: January 2007

Oceanic 87Sr/86Sr‐isotope ratios are strongly influenced by rates of silicate weathering and therefore linked not only to glaciation but also to sea‐level change. The present study combines analysis of sequence stratigraphy and basin architecture with Sr‐isotope stratigraphy in Miocene shallow‐water sediments in southern Portugal and Crete (Greece). The common method is to use smoothed global sea water Sr‐isotope reference curves but here a different approach is chosen. Instead, measured Sr‐isotope curves are correlated with unsmoothed reference curves by identification of similar fluctuations in the order of several 100 kyr. Transgressive intervals are characterized by increasing Sr‐isotope ratios interpreted as corresponding to intensified silicate weathering as a consequence of deglaciation, while lowstand deposits have low Sr‐isotope ratios. Comparison of Sr‐isotope curves and sedimentary sequences in the studied basins with independent global δ18O data and data on global sea‐level might suggest a general relationship, supporting a connection to global climate change. Because of these relationships, the method presented herein has a high potential for use in high‐resolution age dating and is also applicable in shallow‐water sediments.
Polymorphisms of human leucocyte antigen genes in Maonan people in China
Authors: Ogata S. , Shi L. , Matsushita M. , Yu L. , Huang X. Q. , Shi L. , Sun H. , Ohashi J. , Muramatsu M. , Tokunaga K. , Chu J. Y.
Published: January 2007

We examined human leucocyte antigen (HLA) gene polymorphisms in the Maonan people from southern China. HLA‐A, ‐B and ‐DRB1 alleles were determined in 108 healthy unrelated Maonan individuals by the polymerase chain reaction‐Luminex method, and haplotype frequencies for HLA‐A, ‐B and ‐DRB1 loci were estimated. The most frequent HLA‐A alleles were A*1101 (35.2%), A*0203 (17.6%), A*0207 (13.4%) and A*2402 (13.4%); HLA‐B alleles were B*1301(19.9%), B*1502 (14.8%), B*4601 (13.4%) and B*4001 (13.4%); HLA‐DRB1 alleles were DRB1*1202 (17.1%), DRB1*1602 (13.0%) and DRB1*1401 (10.7%). The most common haplotypes were A*0207‐B*4601 (10.6%), A*1101‐B*1301 (10.0%), A*1101‐B*4001 (8.4%), B*1502‐DRB1*1202 (12.0%), B*4601‐DRB1*1401 (5.8%), A*1101‐B*1502‐DRB1*1202 (7.1%) and A*0207‐B*4601‐DRB1*1401 (5.3%), profiles that are also found in populations from the southern region of East Asia. Phylogenetic and principal component analyses revealed that the Maonan people belong to the southeastern Asian group and are most closely related to the Buyi people.
Characterization of HKE2: an ancient antigen encoded in the major histocompatibility complex
Authors: Ostrov D. A. , Barnes C. L. , Smith L. E. , Binns S. , Brusko T. M. , Brown A. C. , Quint P. S. , Litherland S. A. , Roopenian D. C. , Iczkowski K. A.
Published: January 2007

Genes at the centromeric end of the human leukocyte antigen region influence adaptive autoimmune diseases and cancer. In this study, we characterized protein expression of HKE2, a gene located in the centromeric portion of the class II region of the major histocompatibility complex encoding subunit 6 of prefoldin. Immunohistochemical analysis using an anti‐HKE2 antibody indicated that HKE2 protein expression is dramatically upregulated as a consequence of activation. In a tissue microarray and in several tumors, HKE2 was overexpressed in certain cancers compared with normal counterparts. The localization of the HKE2 gene to the class II region, its cytoplasmic expression and putative protein‐binding domain suggest that HKE2 may function in adaptive immunity and cancer.
Characterization of the novel allele HLA‐Cw*0331 by sequence‐based typing†
Authors: Nesci S. , Malagoli A. , Iliescu A. , Buffi O. , Carella G.
Published: January 2007

A novel allele HLA‐C allele, Cw*0331, has been identified by sequence based typing in a German individual selected as a potential bone marrow unrelated donor.
Primary sclerosing cholangitis is associated with extended HLA‐DR3 and HLA‐DR6 haplotypes
Authors: Wiencke K. , Karlsen T. H. , Boberg K. M. , Thorsby E. , Schrumpf E. , Lie B. A. , Spurkland A.
Published: January 2007

Primary sclerosing cholangitis (PSC) is associated with the human leukocyte antigen (HLA)‐DRB1*0301‐DQA1*0501‐DQB1*0201 (DR3) and HLA‐DRB1*1301‐DQA1*0103‐DQB1*0603 (DR6) haplotypes. Recently, the extended HLA class I region has been found to harbour genes that modulate or confer susceptibility independently of the HLA class II genes in several immune‐mediated diseases. The aim of the present study was to evaluate the influence of genes in the extended HLA class I region on susceptibility to PSC. Seven microsatellite markers (MIB, D6S265, D6S2222, D6S464, D6S2223, D6S2225 and D6S2239) were analysed together with HLA class II alleles in 219 Norwegian patients with PSC and 282 random controls. To control for associations because of linkage disequilibrium (LD), 142 HLA‐DR3 homozygous and 187 DR6‐positive controls were included. The unstratified analysis showed significant associations with the alleles MIB*349 [odds ratio (OR) = 3.0, corrected P value (Pc) = 3 × 10−12], D6S265*122 (OR = 1.7, Pc= 0.004), D6S464*209 (OR = 1.8, Pc= 0.03) and D6S2225*147 (OR = 2.7, Pc= 4 × 10−6), which were mainly secondary to the DR3 association. When stratifying for DR6, an association with the D6S265*122 allele was still observed (OR = 3.7, Pc= 0.0004). In the presence of the D6S265*122 allele, the risk to develop PSC conferred by DR6 was increased four times compared with the risk conferred by DR6 alone. In addition, a novel negative association of PSC with DR11 was observed (OR = 0.21, Pc= 2 × 10−4). In conclusion, our study shows that a gene in LD with D6S265 contributes to susceptibility to develop PSC in individuals carrying DR6. Moreover, we found that the PSC‐associated DR3 haplotype extends more telomeric than that previously reported. We also report a possible protective effect of DR11 on development of PSC.
Frequency distribution of cytokine gene polymorphisms in the healthy North Indian population
Authors: Kaur G. , Rapthap C. C. , Kumar N. , Kumar S. , Neolia S. , Mehra N. K.
Published: January 2007

The allelic and genotype frequencies corresponding to 22 single nucleotide polymorphisms (SNPs) in 13 cytokine genes interleukin (IL) 1‐α (T/C −889), IL1‐β (C/T −511, T/C +3962), IL12 (C/A −1188), interferon‐γ (A/T UTR 5644), transforming growth factor‐β (C/T codon 10, G/C codon 25), tumour necrosis factor‐α (G/A −308, G/A −238), IL2 (T/G −330, G/T +160), IL4 (T/G −1098, T/C −590, T/C −33), IL6 (G/C −174, G/A nt 565), IL10 (G/A −1082, C/T −819, C/A −592), IL1R (C/T pst11970), IL1RA (T/C mspa111100) and IL4RA (G/A +1902) were determined in 130 healthy North Indian subjects. All genomic typings were performed with polymerase chain reaction with sequence‐specific assays. An analysis of the allelic and haplotype frequencies in the North Indian population showed a good fit with the Hardy–Weinberg equilibrium for most of the SNPs. The data can be used for anthropological comparisons, as well as for association studies with different diseases and for use in transplant situations involving acute and chronic rejection.
Haplotype‐specific extraction: a universal method to resolve ambiguous genotypes and detect new alleles – demonstrated on HLA‐B
Authors: Nagy M. , Entz P. , Otremba P. , Schoenemann C. , Murphy N. , Dapprich J.
Published: January 2007

Haplotype‐specific extraction (HSE) allows the collection of individual alleles by separating diploid samples into their haploid components. The separation step is performed using magnetic beads in conjunction with allele‐group‐specific probes. The haplo‐separated DNA samples can be directly typed with downstream applications such as sequence‐specific oligonucleotide (SSO) typing, sequence‐specific primer (SSP) typing, and sequence‐based (SB) typing. Here we show that HSE permits the direct sequencing of an allele in its individual, separated state, including previously unknown alleles. Allele pair combinations that cannot be resolved by SSP, SSO, or generic SB typings can be unambiguously typed after the alleles are separated by HSE, which allows for new alleles to be easily detected without cloning. We show how HSE was performed to separate samples with locus‐specific ambiguities in human leukocyte antigen (HLA)‐B, which could not be resolved by means of generic SB typing for either sample. After haplotype‐specific separation of the respective allele pairs, novel polymorphisms in the HLA‐B*56 and HLA‐B*44 alleles were clearly detected by SB typing.
HLA‐E*0101 and HLA‐G*010101 reduce the risk of Behcet’s disease
Authors: Park K. S. , Park J. S. , Nam J. H. , Bang D. , Sohn S. , Lee E. S.
Published: January 2007

The nonclassical human leukocyte antigen (HLA)‐E and ‐G molecules have previously been shown to inhibit natural killer‐ and cytotoxic T‐lymphocyte‐mediated cell lysis and have also been shown to prevent the proliferation of CD4 T cells and secrete cytokines that appear to be important in the modulation of the Behcet’s disease (BD) immune systems. Polymorphisms in the HLA‐E and HLA‐G genes have been associated with differential expression and function. Thus, we conducted an analysis of the HLA‐E and HLA‐G alleles using Amplification Refractory Mutation System‐polymerase chain reaction (PCR) and PCR‐restriction fragment length polymorphism techniques in a study comprising 312 patients with BD and 486 controls. The HLA‐E*0101 and HLA‐G*010101 alleles were associated with a reduced risk of BD (P = 0.0002, odds ratio (OR) = 0.7 and P = 0.002, OR = 0.7, respectively). By way of contrast, the variants HLA‐E*010302, HLA‐G*010102, G*0105N alleles and 3741_3754ins14bp were all associated with an increased risk of BD (P < 0.0001, OR = 1.6; P = 0.002, OR = 1.8; P = 0.024, OR = 2.0 and P = 0.003, OR = 1.4, respectively). Individuals carrying both the HLA‐E*0101 and the HLA‐G*010101 alleles evidenced significantly lower frequency in the patients than in the controls (35.6% vs 49.6%; P < 0.0001, OR = 0.6). These results indicate that variant HLA‐E and HLA‐G molecules appear to function independently and synergistically, increasing the risk of BD, and may result in an imbalance of lymphocytic functions, which may culminate in the development of BD.
Immunogenetics of ocular inflammatory disease
Authors: Levinson R. D.
Published: January 2007

Ocular inflammatory disease comprises of a diverse group of clinical entities that may result from autoimmune processes, infections, or both. While many individual ocular inflammatory diseases are quite rare, ocular inflammation is one of the more common causes of visual disability, including blindness, in the developed world. Better understanding of ocular inflammatory disease is an important step in designing more sophisticated therapies that may help prevent loss of visual function for these patients.
Association between hepatitis B virus infection and HLA‐DRB1 genotyping in Shaanxi Han patients in northwestern China
Authors: Yang G. , Liu J. , Han S. , Xie H. , Du R. , Yan Y. , Xu D. , Fan D.
Published: January 2007

Hepatitis B virus (HBV) infection is a major public health problem worldwide. The mechanism of susceptibility to chronic persistent HBV infection is not well clarified, while the outcome of HBV infection mainly depends on the host immune response. Human leukocyte antigen (HLA) class II molecule is an integral component of the immune response on which majority of host genetic studies have concentrated. Many different HLA class II alleles have been demonstrated to play roles in HBV infection. In this study, the association between HBV infection and HLA‐DRB1 alleles in Han individuals in northwestern China was studied for the first time. Two hundred and fifty Shaanxi Han individuals were categorized into three different groups: the HBV‐infected patient group (n = 108), the spontaneously cleared control group (n = 108) and the unexposed group (n = 34). DRB1*04, DRB1*09, DRB1*12 and DRB1*15 were the most common genotypes in all the groups. The allele frequencies of HLA‐DRB1*03 [10.6% of HBV‐infected patients vs 3.7% of spontaneously cleared controls, odds ratios (OR) = 3.10, Pc = 0.008, P < 0.05] and HLA‐DRB1*07 (17.6% of HBV‐infected patients vs 9.3% of spontaneously cleared controls, Pc = 0.016, OR = 2.09, P < 0.05) were markedly higher in the HBV‐infected group. But the allele frequencies of HLA‐DRB1*15 (6.9% of HBV‐infected patients vs 13.4% of spontaneously cleared controls Pc = 0.039, OR = 0.48, P < 0.05) were obviously lower than that of the spontaneously cleared controls. The above data indicate that HLA‐DRB1*03 and HLA‐DRB1*07 are related to susceptibility to chronic HBV infection, and DRB1*15 is negatively related to persistence to chronic HBV infection among people in northwestern China. Similar results were got for DRB1*03 and 15 alleles between the HBV‐infected patients (n = 108) and 46 HBV seronegative spouses of the HBV patients, who were high‐risk group for HBV infection. The above results suggest that host HLA class II gene is an important factor in determination of the outcome of HBV infection.
Insulin gene VNTR, CTLA‐4 +49A/G and HLA‐DQB1 alleles distinguish latent autoimmune diabetes in adults from type 1 diabetes and from type 2 diabetes group
Authors: Haller K. , Kisand K. , Pisarev H. , Salur L. , Laisk T. , Nemvalts V. , Uibo R.
Published: January 2007

Recent research has underlined the need to explore pathogenic, genetic and clinical spectrum of adult onset autoimmune diabetes, also known as latent autoimmune diabetes in adults (LADA). We aimed to investigate whether genetic factors that are associated with type 1 diabetes (T1D) susceptibility, namely HLA‐DQB1 alleles, cytotoxic T‐lymphocyte antigen 4 gene (CTLA‐4) and insulin gene (INS) polymorphisms, are also associated with an atypical subset of patients diagnosed with type 2 diabetes (T2D). The case–control study included 70 T1D, 305 T2D and 252 nondiabetic controls. The T2D group was divided into atypical T2D (LADA, n = 61) or typical T2D (n = 244) subgroups based on the presence of at least one pancreas‐specific antibody. Our data suggested that HLA‐DQB1 alleles of all three risk classes, INS variable number of tandem repeat (VNTR) I/I and CTLA‐4 +49 GG or AG genotypes, were independent risk factors for developing LADA and could be used as a diagnostic tool to discriminate between LADA and T2D. Additionally, there was an increased association between LADA and CTLA‐4 diabetes‐susceptibility genotypes and decreased association with INS VNTR and high‐risk HLA‐DQB1 alleles, compared with T1D. Our study suggested the need for further investigation into the genetic background and functional genomics of LADA in comparison with T1D and T2D.
Diversity of the killer cell immunoglobulin‐like receptor gene KIR2DS4 in the Chinese population
Authors: Yan L.‐X. , Zhu F.‐M. , Jiang K. , He J.
Published: January 2007

Human killer cell immunoglobulin‐like receptors are a subfamily of the immunoglobulin superfamily, which map to the leukocyte receptor complex on chromosome 19. Here, we established polymerase chain reaction–sequence‐based typing (PCR‐SBT) procedures to identify alleles of the KIR2DS4 gene. The method was designed around the specific amplification of exons 4–5 of the KIR2DS4 gene. Genomic DNA from 105 healthy unrelated Chinese Han individuals were typed for the KIR2DS4 alleles. Each sample was assigned the KIR2DS4 alleles combination, consistent with the pairwise combinations of sequences of all the known KIR2DS4 alleles. We observed eleven different genotypes and four KIR2DS4 alleles in the population, with the KIR2DS4*00101 having the highest frequency, 0.576, and also confirmed the new KIR2DS4*007 allele. Our data demonstrated that the established PCR‐SBT method for the KIR2DS4 allele typing was reliable.
Sequence analysis of the novel allele HLA‐B*5522 in the Chinese population†
Authors: Yan L.‐X. , Zhu F.‐M. , Zhang W.
Published: January 2007

A novel HLA‐B*5522 allele was identified in the Chinese individual by polymerase chain reaction sequence–based typing.
An unlikely rare result of HLA‐A*0236, *3601 masking the presence of a novel allele A*0114†
Authors: Crowley J. , Dunne C. , Cox S. T. , Little A.‐M.
Published: January 2007

We identified an A*0114 allele in an Irish patient with an apparent A*0236, A*3601 type.
A novel HLA‐B*13 allele, B*1314, was found through routine HLA class I sequence‐specific oligonucleotide typing and confirmed by sequence‐based HLA typing†
Authors: Witter K. , Zahn R. , Lübke S. , Albert T. , Kauke T.
Published: January 2007

In this study, we report the identification of HLA‐B*1314 that differs from B*130201 at two single nucleotide positions.
A new human leukocyte antigen DRB1 allele, HLA‐DRB1*1375†
Authors: Sánchez‐Gordo F. , Balas A. , Ortiz M. , Prat I. , Vicario J. L.
Published: January 2007

DRB1*1375 differs from DRB1*1304 allele in a point nucleotide mutation at codon 67 (ATC→TTC), which produces an amino acid residue change from I to F.
Establishment of a sequence‐based typing system for BoLA‐DQA1 exon 2
Authors: Takeshima S. , Miki A. , Kado M. , Aida Y.
Published: January 2007

In cattle, bovine leukocyte antigens (BoLAs) have been extensively used as markers for bovine diseases and immunological traits. Here, we developed a rapid, high‐resolution sequence‐based typing (SBT) system for BoLA‐DQA1. We amplified 355 bp of BoLA‐DQA1 by fully nested polymerase chain reaction (PCR) using the newly constructed primers and then performed direct sequencing of each product. Using this method, we investigated the locus in 51 animals whose BoLA haplotypes had been characterized at the Fifth International BoLA Workshop. We identified 15 distinct DQA1 alleles, and there is no conflict between the typing result of PCR‐SBT and restriction fragment length polymorphism analysis. Together with the previously developed method for typing BoLA‐DRB3, the PCR‐SBT for BoLA‐DQA1 clearly provides a useful tool for detailed class IIa haplotype analysis.
First experiences of pediatric kidney transplantation in Sri Lanka
Authors: Abeysekera C. K. , Gunasekara W. D. V. N. , Abegunawardena A. , Buthpitiya A. G. , Lamawansa M. D. , Fernando O. , Goonasekera C. D. A.
Published: February 2007

Abstract:  KT is the most effective therapeutic option for ESRF. We present our first experiences in a developing country. All children who underwent kidney transplantation since the inception of this program in July 2004 until 30 September 2005 were studied. Their demographic data, operative and peri‐operative details, graft and host survival, and drug compliance are described here. Data were collected from patient records and nursing observation records. Eleven children were transplanted during this period (median recipient age 10.75 yr, range: 8–16). The median age of the donors was 41 yr (range: 38–45) and was the mother in eight, father in two and uncle in one. The median (range) follow‐up period following transplantation was 12.5 months (7–12). The vascular anastomotic site was aorta and inferior vena cava in nine patients and the cold ischemia time was mean (s.d.) 1.9 h (0.96). All patients received steroids, cyclosporine and MMF for immunosuppression. Hypotension, heart failure and septicemia were common medical complications. Four were treated for acute rejection. Vascular anastomotic leak, burst abdomen, intestinal obstruction, intra‐abdominal leak of supra pubic catheter and vesico‐ureteric junction obstruction were surgical complications. There were no graft losses or deaths. Despite limited resources good outcomes are possible following renal transplantation in children in developing countries.
Cavernous hemangioma in the ascending colon treated by endoscopic mucosal resection
Authors: Kimura Shigeru , Tanaka Shinji , Kusunoki Hiroaki , Kitadai Yasuhiko , Sumii Masaharu , Tazuma Susumu , Yoshihara Masaharu , Haruma Ken , Chayama Kazuaki
Published: January 2007

Hemangioma of the large intestine is rare, but it is a clinically important entity because of the possibility of massive hemorrhage. The case is reported of a patient with a formed, sessile, polypoid‐type cavernous hemangioma in the ascending colon that was removed successfully by endoscopic mucosal resection.
Mechanism of impaired regeneration of fatty liver in mouse partial hepatectomy model
Authors: Murata Hiroshi , Yagi Takahito , Iwagaki Hiromi , Ogino Tetsuya , Sadamori Hiroshi , Matsukawa Hiroyoshi , Umeda Yuzoh , Haga Sanae , Takaka Noriaki , Ozaki Michitaka
Published: January 2007

Background and Aim:  The mechanism of injury in steatotic liver under pathological conditions been extensively examined. However, the mechanism of an impaired regeneration is still not well understood. The aim of this study was to analyze the mechanism of impaired regeneration of steatotic liver after partial hepatectomy (PH).

Methods:  db/db fatty mice and lean littermates were used for the experiments. Following 70% PH, the survival rate and recovery of liver mass were examined. Liver tissue was histologically examined and analyzed by western blotting and RT‐PCR.

Results:  Of 35 db/db mice, 25 died within 48 h of PH, while all of the control mice survived. Liver regeneration of surviving db/db mice was largely impaired. In db/db mice, mitosis of hepatocytes after PH was disturbed, even though proliferating cell nuclear antigen (PCNA) expression (G1 to S phase marker) in hepatocytes was equally observed in both mice groups. Interestingly, phosphorylation of Cdc2 in db/db mice was suppressed by reduced expression of Wee1 and Myt1, which phosphorylate Cdc2 in S to G2 phase.

Conclusions:  In steatotic liver, cell‐cycle‐related proliferative disorders occurred at mid‐S phase after PCNA expression. Reduced expression of Wee1 and Myt1 kinases may therefore maintain Cdc2 in an unphosphorylated state and block cell cycle progression in mid‐S phase. These kinases may be critical factors involved in the impaired liver regeneration in fatty liver.