bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment of an infectious genotype 1b hepatitis C virus clone in human hepatocyte chimeric mice
Authors: Kimura Takashi , Imamura Michio , Hiraga Nobuhiko , Hatakeyama Tsuyoshi , Miki Daiki , Noguchi Chiemi , Mori Nami , Tsuge Masataka , Takahashi Shoichi , Fujimoto Yoshifumi , Iwao Eiji , Ochi Hidenori , Abe Hiromi , Maekawa Toshiro , Arataki Keiko , Tateno Chise , Yoshizato Katsutoshi , Wakita Takaji , Okamoto Toru , Matsuura Yoshiharu , Chayama Kazuaki
Published: August 2008

The establishment of clonal infection of hepatitis C virus (HCV) in a small-animal model is important for the analysis of HCV virology. A previous study developed models of molecularly cloned genotype 1a and 2a HCV infection using human hepatocyte-transplanted chimeric mice. This study developed a new model of molecularly cloned genotype 1b HCV infection. A full-length genotype 1b HCV genome, HCV-KT9, was cloned from a serum sample from a patient with severe acute hepatitis. The chimeric mice were inoculated intrahepatically with in vitro-transcribed HCV-KT9 RNA. Inoculated mice developed viraemia at 2 weeks post-infection, and this persisted for more than 6 weeks. Passage experiments indicated that the sera of these mice contained infectious HCV. Interestingly, a similar clone, HCV-KT1, in which the poly(U/UC) tract was 29 nt shorter than in HCV-KT9, showed poorer in vivo infectivity and replication ability. An in vitro study showed that no virus was produced in the culture medium from HCV-KT9-transfected cells. In conclusion, this study developed a genetically engineered genotype 1b HCV-infected mouse. This mouse model will be useful for the study of HCV virology, particularly the mechanism underlying the variable resistance of HCV genotypes to interferon therapy.
Performance Management and the Psychological Contract in the Australian Federal Public Sector
Authors: O’Donnell Michael , Shields John
Published: August 2008

This study explores employee responses to individual performance management practices in two culturally dissimilar agencies of the federal public sector, the Department of Finance and Administration (DOFA) and the Australian Defence Force (Army). In so doing, it invokes Rousseau’s distinction between ‘relational’ and ‘transactional’ psychological contracts and Guest’s model of the causes, content and consequences of the psychological contract. In DOFA, neither system processes nor outcomes have lived up to the high employee expectations built up by management discourse about a new transactional culture of high rewards for performance excellence. Conversely, in the Army, expectations are less inflated, the constraints on promotion-based rewards are well understood and the system of developmental appraisal provides solid reinforcement for the prevailing hierarchical culture with its characteristic emphasis on a relational psychological contract. These findings raise doubts about whether individual performance pay is appropriate for public sector staff. They also suggest that the achievement and maintenance of a positive psychological contract requires close attention to the full range of causal factors, including human resource practices used as well as the modes of organisational communication in use, the contours of organisational culture, and employees’ prior experience and expectations.
Practice of venom immunotherapy in the United Kingdom: a national audit and review of literature
Authors: Diwakar L. , Noorani S. , Huissoon A. P. , Frew A. J. , Krishna M. T.
Published: August 2008

Background
Venom immunotherapy (VIT) is the only effective treatment for prevention of serious allergic reactions to bee and wasp stings in sensitized individuals. However, controversies exist relating to diagnosis, indications for treatment and treatment schedules. We audited current practice of VIT in the United Kingdom to evaluate adherence to international guidelines.

Methods
An online questionnaire was sent to all clinicians practising immunotherapy identified on the British Society of Allergy and Clinical Immunology website. Eighty‐six questionnaires were sent and 53 responses (61.6%) were received. Of these, 48 (85%) carried out VIT at their centre.

Results
Skin prick tests (SPT) and serum venom‐specific IgE (SSIgE) were equally preferred as first‐line investigation. Fifty percent of the respondents perform intradermal tests if both SPT and SSIgE are negative. While 8% of respondents commence VIT in patients with negative SSIgE and a history of severe reaction, 57% prefer to repeat the tests in 6–12 months if serum tryptase is elevated. If the insect responsible is uncertain and SSIgE is detected against bee and wasp venoms, 22% of the respondents will desensitize to both while 32% initiate treatment against the venom with the higher SSIgE. A protocol of weekly up‐dosing for 12 weeks is preferred for induction and only 25% of respondents have ever used rush or ultra‐rush protocols. Three years is thought to be optimum duration of VIT by most (56%). Eleven percent perform sting challenges at the end of treatment. Although 47% measure SSIgE at the end of treatment, only 3% use these results as a basis for discontinuing VIT.

Conclusion
Currently there is considerable variation in the diagnosis and management of hymenoptera venom allergy in the United Kingdom. This audit has demonstrated that the current international guidelines for the diagnosis and management of hymenoptera venom allergy are not being followed by UK allergy practitioners.
Association of angiotensin I‐converting enzyme gene polymorphisms with aspirin intolerance in asthmatics
Authors: Kim T‐H. , Chang H‐S. , Park S‐M. , Nam B‐Y. , Park J‐S. , Rhim T. , Park H‐S. , Kim M‐K. , Choi I. S. , Cho S. H. , Chung I. Y. , Park B‐L. , Park C‐S. , Shin H‐D.
Published: August 2008

BackgroundAspirin‐intolerant asthma (AIA) refers to the development of bronchoconstriction in asthmatic individuals following the ingestion of aspirin or other non‐steroidal anti‐inflammatory drugs (NSAIDs). Angiotensin I‐converting enzyme (ACE), a membrane‐bound peptidase present in the lung, plays a pivotal role in the metabolism of the endogenous peptides involved in the pathogenesis of asthma.

MethodsWe screened a Korean asthma cohort (581 asthmatics including 81 aspirin‐intolerant asthmatics and 231 aspirin‐tolerant asthmatics, and 181 normal controls) for four single nucleotide polymorphisms (SNPs; −262 A>T and −115 T>C in the 5′‐flanking region and +5467 T>C [Pro450Pro] and+11860 A>G [Thr776Thr] in the coding region) and one ins/del (+21288 CT) in theACEgene.

ResultsNone of the SNPs or haplotypes showed any association with the development of asthma, but they were significantly associated with the risk of AIA. Logistic regression indicated that the frequency of the rare alleles of −262 A>T and −115 T>C was higher in subjects with AIA than in subjects with aspirin‐tolerant asthma (ATA) (P=0.003–0.01,P corr=0.015–0.05). Subjects homozygous for the rare alleles of −262 A>T and −115 T>C showed a greater decline in forced expiratory volume in 1 s (FEV1) after aspirin provocation than those homozygous for the common alleles (P<0.05). A luciferase reporter assay indicated thatACEpromoters containing the rare −262 A>T allele possessed lower activity than did those containing the common allele (P=0.009). In addition,ACEpromoters bearing the rare −115 T>C allele had no luciferase activity. DNA–protein binding assays revealed a band containing theACEpromoter region (including −262 A) and a protein complex.

ConclusionThe −262 A>T polymorphism in the promoter of theACEgene is associated with AIA, and the rare allele of −262 A>T may confer aspirin hypersensitivity via the down‐regulation ofACEexpression.
Reference limits of serum TSH and free T4 are significantly influenced by race and age in an urban outpatient medical practice
Authors: Boucai Laura , Surks Martin I.
Published: August 2008

Objective  The suitability of TSH reference limits derived from national databases to outpatient practices has not been established. We aimed to determine whether race and age influence the distribution of TSH and free T4 (fT4).

Design  A cross‐sectional study of an urban outpatient medical practice.

Participants  Patients (n = 22 116) without clinical evidence of thyroid disease or use of thyroid‐specific medications.

Measurements  Comparison of TSH and fT4 distributions in specific racial and age groups including blacks, whites and Hispanics.

Results  TSH was distributed at higher concentrations, without skew, in whites compared to blacks (median, 1·54 mIU/l vs. 1·18 mIU/l, P < 0·001) and in old (>80 years old) compared to young (20–29 years old) (median, 1·61 mIU/l vs. 1·13 mIU/l, P < 0·001). In all patients, blacks and whites, 3%, 8% and 5%, respectively, of those aged > 80 years were misclassified as having high TSH compared to those aged 20–29 years (P < 0·001). Using TSH limits from national databases resulted in significant misclassification of patients with raised or lowered TSH. Mean fT4 was significantly lower in blacks than whites (17·5 ± 4·38 pmol/l vs. 18·3 ± 3·99 pmol/l, P < 0·001), did not differ between young and old, but decreased progressively (average 7%) as TSH increased to > 4·5 mIU/l.

Conclusions  Reference limits for TSH differ between races and with age. Use of race‐ and age‐specific reference limits decreases misclassification of patients with lowered or raised TSH in an urban practice. The unique fT4:TSH relationships of blacks and whites may be genetically determined. The implications of the small decrement in fT4 as TSH increases remain to be explored.
The response of Vallisneria spinulosa (Hydrocharitaceae) to different loadings of ammonia and nitrate at moderate phosphorus concentration: a mesocosm approach
Authors: LI WEI , ZHANG ZHAO , JEPPESEN ERIK
Published: August 2008

1. While phosphorus (P) is often considered the most important growth limiting factor for plants in lakes, recent studies of shallow lakes indicate that nitrogen (N) may be of greater importance than realized hitherto and that submerged macrophytes may be lost when the N concentration exceeds a certain threshold, as long as the concentration of P is sufficiently high.

2. We studied the effects of different loadings of NH4‐N and NO3‐N on chlorophyll a and on a macrophyte tolerant of eutrophication, Vallisneria spinulosa (Hydrocharitaceae). In outdoor mesocosms we used water from a pond as control and created four levels of NH4‐N and NO3‐N (approximately 2.5, 5, 7.5 and 10 mg L−1) by dosing with NH4Cl and NaNO3, respectively. After the experiment, the plants were transferred back to a holding pond to study their recovery. In contrast to previous research, we used a low background concentration of phosphorus (TP 0.024 ± 0.003 mg L−1) so we could judge whether any effects of N were apparent when P is in short supply.

3. Chlorophyll a increased significantly with N dosing for both forms of N, but the increase was highest in the NH4‐N dosed mesocosms (maximum 58 μg L−1 versus 42 μg L−1 in the NO3‐N mesocosms), probably due to a higher total inorganic N concentration (part of the added ammonia was converted to nitrate during the experiment).

4. Although the number of ramets of V. spinulosa was not affected by the N treatment, the biomass increased up to concentrations of 7.5 mg L−1, while biomass at 10 mg L−1 remained at the control level for both N ions treatments. A similar pattern was apparent for the content of N and soluble sugar of the plant, while there were no differences in the plant P content among treatments. Five months after transplantation back to the pond no difference was found in the number of ramets or in biomass, except that the biomass of plants grown at 10 mg N L−1 during the experiment was greater than that in the control, while the N and P contents of plants were similar to those of the controls.

5. Nitrogen concentration had little influence on the growth of the eutrophication tolerant submerged macrophyte at moderately low concentrations of phosphorus. Moreover, the two N ions showed no toxic effects, suggesting that loss of macrophytes observed in other studies, run at higher phosphorus concentrations, was probably related to enhanced shading by periphyton and/or phytoplankton rather than to any toxic effects of N.
Orthopaedic surgery in haemophilia patients with inhibitors: a practical guide to haemostatic, surgical and rehabilitative care
Authors: TEITEL J. M. , CARCAO M. , LILLICRAP D. , MULDER K. , RIVARD G. E. , ST‐LOUIS J. , SMITH F. , WALKER I. , ZOURIKIAN N.
Published: August 2008

Summary.  All but essential surgery is generally avoided in haemophilia patients with inhibitor antibodies, because of concern about the reliability with which haemostasis can be achieved and maintained in such patients. Orthopaedic surgical procedures which are not required to preserve life fall under this category. As a result, patients with inhibitors may be denied operations, which could greatly enhance their quality of life, and which are routinely offered to other haemophilia patients. While caution is appropriate in recommending surgery in any circumstance, we believe that the threshold for offering validated surgical procedures to patients with inhibitors should be re‐evaluated in the light of current surgical and rehabilitative techniques, and the long experience with safe and effective factor VIII inhibitor bypassing agents, namely activated prothrombin complex concentrates and recombinant activated factor FVII. In this article, we review the haematological, surgical and rehabilitative considerations relevant to orthopaedic surgery in haemophilia patients with inhibitors, and provide recommendations for carrying out such procedures.
Current review on squamous intraepithelial lesions of the larynx
Authors: Gale Nina , Michaels Leslie , Luzar Bostjan , Poljak Mario , Zidar Nina , Fischinger Janez , Cardesa Antonio
Published: August 2008

Squamous intraepithelial lesions (SILs) of the larynx, clinically usually defined as leukoplakia and chronic laryngitis, have remained the main controversial topic in laryngeal pathology for decades as regards classification, histological diagnosis and treatment. SILs are caused by smoking and alcohol abuse. There is also mounting evidence that gastroesophageal reflux is a potential aetiological factor. Human papillomavirus infection seems to play little if any role in laryngeal carcinogenesis.

Histological classification of SILs is the central disputed aspect of these lesions. There are as yet no generally accepted criteria for histological grading of laryngeal SILs. Three currently used classifications of SILs are reviewed here: the dysplasia system, the Ljubljana classification and the binary system of squamous intraepithelial neoplasia. One of the most important issues of SILs is the risk of malignant transformation. Data in the literature are controversial because of inconsistent use of morphological criteria in different classifications. It is often difficult for clinicians to agree on the most appropriate therapeutic option for a particular grade of SIL that has been diagnosed. Transition from normal epithelium to SILs and squamous cell carcinoma is related to progressive accumulation of genetic changes leading to a clonal population of transformed epithelial cells. Despite extensive research into these genetic changes in laryngeal carcinogenesis, reliable genetic markers with diagnostic and prognostic value are still lacking.
Dendritic cells modulated by innate immunity improve collagen‐induced arthritis and induce regulatory T cells in vivo
Authors: Jaen Olivier , Rullé Sandrine , Bessis Natacha , Zago Abokouo , Boissier Marie‐Christophe , Falgarone Géraldine
Published: August 2008

Dendritic cells (DCs) mediate interactions between innate and specific immunity and may induce regulatory mechanisms. We investigated the effects of modulated DCs in mice with collagen‐induced arthritis (CIA) and tested the responses of cells to induced naturally occurring regulatory T cells. DCs were stimulated or not with DNA or lipopolysaccharide (LPS) for 24 hr. DC maturation was assayed, and then modulated DCs were intraperitoneally injected on day 14 into DBA/1 mice to treat CIA. In addition to arthritis scores and type 2 collagen (CII) response, the induction of CD4+ CD25+ T cells was analysed by flow cytometry in peripheral blood and the expression of Foxp3, transforming growth factor (TGF)‐β, interleukin (IL)‐10 and cytotoxic T‐lymphocyte antigen (CTLA)‐4 was quantified. Finally, the expression of indoleamine‐2,3‐dioxygenase (IDO) was assayed in DCs. In comparison with LPS‐stimulated DCs, plasmid‐stimulated DCs expressed lower levels of major histocompatibility complex (MHC) class II, CD40, CD80 and CD86 molecules and secreted less IL‐12p70, interferon (IFN)‐γ, IL‐10 and TNF‐α, displaying a semi‐mature phenotype. Compared with non‐stimulated DCs, stimulated DCs improved arthritis scores when injected after immunization, without modifying the T helper type 1 (Th1)/Th2 balance of the immune response against collagen. Stimulated DCs induced markers for regulatory T cells (Foxp3, TGF‐β1 and CTLA‐4) in vivo. Only LPS‐stimulated DCs expressed IDO, which may explain their better therapeutic efficacy. Regulatory mechanisms were induced using DCs modulated by innate immunity stimulators. Innate immunity mechanisms do not require the presence of the disease‐causing antigen, even in T‐ and B‐cell specific diseases. Our results have implications for the treatment of rheumatoid arthritis, an autoimmune disease whose triggering antigen has not been identified, and substantially clarify the role of regulatory T cells in CIA.
Selective impairment in dendritic cell function and altered antigen‐specific CD8+ T‐cell responses in diet‐induced obese mice infected with influenza virus
Authors: Smith Alexia G. , Sheridan Patricia A. , Tseng Raymond J. , Sheridan John F. , Beck Melinda A.
Published: August 2008

There is a clear link between obesity and metabolic disorders; however, little is known about the effect of obesity on immune function, particularly during an infection. We have previously reported that diet‐induced obese mice are more susceptible to morbidity and mortality during influenza infection than lean mice. Obese mice displayed aberrant innate immune responses characterized by minimal induction of interferon (IFN)‐α/β, delayed expression of pro‐inflammatory cytokines and chemokines, and impaired natural killer cell cytotoxicity. To further examine the abnormal immune response of diet‐induced obese mice, we analysed the cellularity of their lungs during influenza virus infection. We found delayed mononuclear cell entry with a marked decrease in dendritic cells (DCs) throughout the infection. Given the critical role of the DC in activating the cell‐mediated immune response, we also analysed the functional capacity of DCs from obese mice. We found that, while obesity did not interfere with antigen uptake and migration, it did impair DC antigen presentation. This was probably attributable to an altered cytokine milieu, as interleukin (IL)‐2, IL‐12, and IL‐6 were differentially regulated in the obese mice. Overall, this did not impact the total number of virus‐specific CD8+ T cells that were elicited, but did affect the number and frequency of CD3+ and CD8+ T cells in the lung. Thus, obesity interferes with cellular responses during influenza infection, leading to alterations in the T‐cell population that ultimately may be detrimental to the host.
Acute hepatitis A in Italy: incidence, risk factors and preventive measures
Authors: Tosti M. E. , Spada E. , Romanò L. , Zanetti A. , Mele A. ,   on behalf of the SEIEVA collaborating group
Published: August 2008

Summary.  The incidence of, and risk factors for, acute hepatitis A (AHA) were assessed by using data collected from the Italian surveillance system of acute viral hepatitis (SEIEVA). To this end, a case–control study within a population‐based surveillance for acute viral hepatitis was performed. AHA incidence has been estimated since 1991; the association with considered risk factors was analysed from 2001 to 2006 employing cases of acute hepatitis B (AHB) as controls. The incidence of AHA declined from 4 / 100 000 in 1991 to 1.4/100 000 in 2006, with a peak during 1996–1998 due to an outbreak in southern Italy. The incidence of AHA was highest among persons aged 15–24 years. The case‐fatality rate was 2.9 / 10 000. Contact with individuals with AHA [adjusted OR (ORadj) = 3.8, 95% CI 2.7–5.5; population‐attributable risk (PAR) = 7.5%], travelling to endemic areas (ORadj = 3.1, 95% CI = 2.6–3.8; PAR = 19.5%), ingestion of raw shellfish (ORadj = 1.8, 95% CI = 1.6–2.1; PAR = 26.6%), and cohabitation with day care children (ORadj = 1.3, 95% CI = 1.01–1.7; PAR = 2.3%) were the main important risk factors. In 2003, an outbreak, with high case‐fatality rate occurred among intravenous drug users, in a central Italian town. A weak association was found for male homosexuality when acute hepatitis C cases were employed as controls (ORadj = 1.4 CI, 95% CI = 1.1–1.9). Hepatitis A virus infections are currently occurring more frequently in adults, in whom the disease is most severe. In conclusion, looking at the attributable risks, at present most of the AHA infections are due to shellfish consumption, travel to endemic areas and contact with patients with AHA. Vaccination of individuals at increased risk of infection, as well as persons with underling liver disease and those at increased risk of complications, combined with surveillance of shellfish retail outlets are efficient control measures.
Decline in the risk of hepatitis A virus infection in China, a country with booming economy and changing lifestyles
Authors: Xu Zhi‐Yu , Wang Xuan‐Yi , Liu Chang‐Qing , Li Yang‐Ting , Zhuang Fang‐Chen
Published: August 2008

Summary.  The objective of the study was to identify the protective factors for the rapid decline in the risk of hepatitis A virus (HAV) infection in China between 1990 and 2006. Results of serological follow‐up and data on annual hepatitis A incidence were analysed and correlated with economic growth and HAV vaccine output during the same period. In conclusion, both HAV vaccination and changing lifestyles associated with the booming economy contributed to the rapid risk decline. Changing lifestyles played a major role in the decline especially in the areas with booming economy.
Modern epidemiology of hepatitis A in the north‐western region of the Russian Federation
Authors: Shliakhtenko L. , Plotnikova V. , Levakova I. , Rubis L. , Solovieva E. , Mukomolov S.
Published: August 2008

Summary.  The epidemiological features of hepatitis A virus (HAV) infection were studied in eleven territories located in the north‐western region of the Russian Federation. The dynamics of HAV infection in Russia and in the region were evaluated during a 17‐year period. The age‐specific incidence was calculated and 229 305 patients with acute HAV were identified. The analysed database included HA mixed with other viral hepatitis infections: it included information about 8 809 HAV patients. Special attention has been paid to the sero‐epidemiological studies conducted in St Petersburg city. These studies included analysis of age‐specific incidence in persons 20 years of age and older during 6 years and testing of blood sera from 1 892 healthy persons for IgG anti‐HAV. In general there is a trend to reduction of HAV incidence in Russia, and in the north‐western region, high indices were registered in some provinces in different years. It was established three types of age‐specific incidence distribution: predominated incidence in 3–14 years of age (first type), 15–29 years of age (second type) and uniform distribution in different age groups (third type). It was shown that decrease of HAV incidence in children and young adults lead to the reduction of sero‐positivity level in the groups 20+ years of age. These characteristics should be taken in account to define indications for HAV vaccine prophylaxis. HAV infection in 10–13% of cases mixed with acute or chronic hepatitis B and C in the last 15 years in St Petersburg. In the middle of 1990s, HAV mostly mixed with acute viral hepatitis of different aetiology, but in the modern time predominated type of mixture was presented by HAV and chronic HBV and HCV infections. The obtained results are useful for viral hepatitis surveillance and control.
Hepatitis A acute liver failure: follow‐up of paediatric patients in southern Brazil
Authors: Ferreira C. T. , Vieira S. M. G. , Kieling C. O. , Silveira T. R.
Published: August 2008

Summary.  We retrospectively analysed 33 children and adolescents who had been hospitalized in a liver transplant unit within the previous 10 years for acute liver failure (ALF). The patients’ age varied between 2 months and 15 years of age (median 6.2 ± 5.3), and 21 (63%) were male. Thirteen patients (39%) were immunoglobulin‐M anti‐hepatitis A virus (HAV) sero‐positive. Eleven cases (33%) had an undetermined aetiology. The 13 children with HAV ALF were between 17 months and 15.6 years of age (median 5.8 ± 4.6) and eight were male (61.5%). All were on a list for urgent liver transplant. Of these, five (38%) died while waiting for a liver. Only one patient recovered spontaneously. Seven patients received a liver transplant; three died in the immediate postoperative period and one died 45 days after transplant. Three children are alive 1, 2 and 5 years after transplant. We conclude that HAV was the most frequent cause of ALF, which had high mortality even when a liver transplant was possible. The results support universal HAV vaccination in this area.
Development of an ELA‐DRA gene typing method based on pyrosequencing technology
Authors: Díaz S. , Echeverría M. G. , It V. , Posik D. M. , Rogberg‐Muñoz A. , Pena N. L. , Peral‐García P. , Vega‐Pla J. L. , Giovambattista G.
Published: August 2008

The polymorphism of equine lymphocyte antigen (ELA) class II DRA gene had been detected by polymerase chain reaction–single‐strand conformational polymorphism (PCR‐SSCP) and reference strand‐mediated conformation analysis. These methodologies allowed to identify 11 ELA‐DRA exon 2 sequences, three of which are widely distributed among domestic horse breeds. Herein, we describe the development of a pyrosequencing‐based method applicable to ELA‐DRA typing, by screening samples from eight different horse breeds previously typed by PCR‐SSCP. This sequence‐based method would be useful in high‐throughput genotyping of major histocompatibility complex genes in horses and other animal species, making this system interesting as a rapid screening method for animal genotyping of immune‐related genes.
Characterisation of two novel HLA alleles, HLA‐Cw*0429 and HLA‐DRB3*0223
Authors: Danzer M. , Polin H. , Hofer K. , Pröll J. , Gabriel C.
Published: August 2008

We report here the novel human leukocyte antigens (HLA)‐Cw*0429 and HLA‐DRB3*0223 alleles identified during routine cord blood characterisation by sequence‐based typing.
Sibship size and prevalence of allergic disorders in Japan: The Ryukyus Child Health Study
Authors: Ohfuji Satoko , Miyake Yoshihiro , Arakawa Masashi , Tanaka Keiko , Sasaki Satoshi
Published: August 2008

A number of epidemiological studies have reported an inverse association between increasing sibship size and allergic disorders. The present cross‐sectional study assessed the association between the number of siblings and the prevalence of allergic disorders during the past 12 months in Japanese schoolchildren. Study subjects were 22,750 children aged 6–15 yr in Okinawa. The outcomes were based on diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Adjustment was made for age, gender, maternal age at childbirth, duration of breastfeeding, region of residence, smoking in the household, paternal and maternal history of asthma, atopic eczema, and allergic rhinitis, and paternal and maternal educational level. Significant exposure–response associations were observed between increasing total sibship size and all outcomes under investigation. Having two or more older siblings was significantly inversely related to the prevalence of atopic eczema and allergic rhinoconjunctivitis, but not wheeze or asthma. Having two or more younger siblings was independently associated with a decreased prevalence of atopic eczema, but not wheeze, asthma, or allergic rhinoconjunctivitis. The inverse relationships between sibship size and the prevalence of allergic disorders under study were weakened with advancing age, although the interactions between age groups were not statistically significant. No significant interactions were found in the association of having three or more siblings with allergic disorders between children with a positive or negative parental allergic history. These results are likely to support the in utero programming hypothesis because it is probable that the in utero environment would change with parity, although our observations could not refute the hygiene hypothesis.
On identifiability of (co)variance components in animal models with competition effects
Authors: Cantet R.J.C. , Cappa E.P.
Published: August 2008

There is an increased interest in estimating the (co)variance components of additive animal models with direct and competition effects (AMC). However, some attempts to estimate the dispersion parameters in different animal species faced problems of convergence or inaccurate estimates when pen effects entered the model. We argue that the problem relates to lack of identifiability of the (co)variance components in some AMC. The check for identifiability of the dispersion parameters in mixed models with linear (co)variance structure requires that all the eigenvalues of the restricted maximum likelyhood information matrix (I(θ)) be positive. We show, by way of simple numerical examples, that the singularity of I(θ) is due to confounding between fixed pen effects and the additive competition effects (SBVs). It is also observed that setting pen effects as random does not always remedy the collinearity with SBVs. An alternative AMC is presented in which the incidence matrix of the SBVs can be written as a function of the ‘intensity of competition’ (IC) among animals in the same pen. Examples are presented in which the ICs are related to time. The distribution of families of full and half sibs across pens also plays a role in the identifiability and asymptotic variances of the (co)variance components.
Employer‐sponsored occupational therapy professional development in a multicampus facility: A quality project
Authors: Cusick Anne , Convey Monica , Novak Iona , McIntyre Sarah
Published: August 2008

Aim:  To critically assess and develop recommendations for professional development (PD) for occupational therapists in a multisite specialist cerebral palsy occupational therapy service.

Method:  Quality improvement project based on principles of participatory action research: audit of PD resources/activity; stakeholder consultations and literature review.

Results:  The PD program goal, resources, strategies, activities and evaluations conducted at the centre were identified and described. Areas for improvement were identified by critically considering the PD program in the context of reviewed literature. There was an assumption that personal change through PD would help attain the organisational goal of clinically competent practitioners who use evidence‐based practice in a family‐centred context.

Recommendations:  Future PD plans and evaluations need to explicitly address this assumption. The use of structured reflection and the ‘clinical reasoning’ conceptual framework was recommended as one way to help personal change from PD to have workplace impact. This project provides a precedent and guide to occupational therapy PD planners regarding a whole‐of‐organisation approach to developing and maintaining competence through PD.
Interrater reliability of the Personal Care Participation Assessment and Resource Tool (PC‐PART) in a rehabilitation setting
Authors: Turner Christopher , Fricke Janet , Darzins Peteris
Published: August 2008

Background:  The Personal Care Participation Assessment and Resource Tool (PC‐PART), formerly the Handicap Assessment and Resource Tool (HART), assesses the domains of clothing, hygiene, nutrition, mobility, safety, residence and supports.

Aim:  To examine the interrater reliability of the PC‐PART in a rehabilitation setting.

Methods:  Assessments made by the researcher were compared to the interdisciplinary rehabilitation team. The research and standard assessments occurred within three working days. Raters were blind to each other's scores. Sample participants were a consecutive case‐series of rehabilitation clients with varied diagnoses, activity limitations and participation restrictions. Of 66 consecutive patients seen during the a priori determined enrolment period, 25 were included in the study (nine males and 16 females, aged 44–85 years). The remaining 41 patients did not meet the inclusion criteria.

Conclusion:  The PC‐PART has good interrater reliability. Clinicians, administrators and researchers can be reassured about this aspect of the validity of the tool.
Reliability of the Perceive, Recall, Plan and Perform System of Task Analysis: A criterion‐referenced assessment
Authors: Nott Melissa T. , Chapparo Christine , Heard Robert
Published: August 2008

Objective:  To conduct preliminary examination of the rater and test‐reliability of the Perceive, Recall, Plan and Perform (PRPP) System of Task Analysis, an ecological measure designed to assess task‐embedded information processing capacity during occupational therapy assessment of confused and agitated adults following traumatic brain injury.

Methods:  Occupational therapists observed and scored client performance using the PRPP System of Task Analysis. Correlational analysis and measures of agreement were performed to determine interrater and intrarater reliability. Test procedures were examined for reliability and internal consistency.

Results:  Interrater and test reliability considered three factors: therapists, clients and tasks. A moderate level of interrater reliability was achieved between trained therapists (intraclass correlation coefficient (ICC) = 0.60). Test procedures were highly reliable (ICC = 0.88). Across two measurement occasions, therapists showed a tendency towards harder rating on the second test occasion (

 –4.5%; 95% confidence interval for

: –10.67%→ 3.17%).

Conclusion:  The findings of this study support the use of criterion‐referenced tests in the area of occupational performance measurement. Occupational therapists achieved moderate interrater reliability when measuring the performance of adults with brain injury on various activities of daily living. Test procedures were found to be highly reliable in measuring the occupational performance of adults demonstrating confusion and agitation typical to the stage of post‐traumatic amnesia following head injury.
Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease
Authors: Naderi Nosratollah , Farnood Alma , Habibi Manijeh , Derakhshan Faramarz , Balaii Hedieh , Motahari Zahra , Agah Mohammad R , Firouzi Farzad , Rad Mahta G , Aghazadeh Rahim , Zojaji Homayoun , Zali Mohammad R
Published: August 2008

Background and Aims: The vitamin D receptor (VDR) gene maps to a region on chromosome 12 shown to be linked to inflammatory bowel disease (IBD). Many studies have recognized the relation of VDR gene polymorphisms with inflammatory and autoimmune disorders. Determining the frequency of these polymorphisms and their possible relation with IBD can improve understandings about the genetic background of these diseases. The objective of this study was to assess the association of VDR gene polymorphisms (Apa I, Taq I, Bsm I, Fok I) with IBD in Iran.

Methods: In this case control designed study 150 patients with ulcerative colitis, 80 patients with Crohn's disease and 150 Age and Sex matched healthy controls from Iranian origin were enrolled. These patients were referred to a tertiary center during a two‐year period (2004–2006). Assessment of VDR gene polymorphisms was performed by the polymerase chain reaction—restriction fragment length polymorphism (PCR‐RFLP) method. The genotype–phenotype association for these polymorphisms was analyzed.

Results: Only the frequency of the Fok I polymorphism was significantly higher in ulcerative colitis and Crohn's groups. The frequency of the polymorphic allele f was higher in ulcerative colitis and Crohn's patients comparing with controls (P = 0.011 andP < 0.001, respectively). The f/f genotype was also significantly more frequent (P < 0.001), while the F/F genotype was less presented in Crohn's patients compared to controls (P < 0.001). No genotype–phenotype association was observed with any mutations.

Conclusions: This study suggests a probable association of the Fok I polymorphism in VDR receptor gene and Crohn's susceptibility in Iranian population.
Clinical experiences of solid pseudopapillary tumors of the pancreas in China
Authors: Yang Feng , Fu De‐liang , Jin Chen , Long Jiang , Yu Xian‐jun , Xu Jin , Ni Quan‐xing
Published: August 2008

Aims:  To discuss the clinical experiences of solid pseudopapillary tumors (SPTs) of the pancreas by summarizing clinical information of patients with this disease in China.

Methods:  Chinese literature concerning SPTs of the pancreas published between January 1996 and October 2006 were retrospectively reviewed and analyzed.

Results:  A total of 390 cases had been reported, among which 47 were men, with a female to male ratio of 7.30:1. Mean age of the patients was 25.3 years old, more than 50 per cent were between 10 and 24 years. The mean diameter of the tumor was 8.4 cm (range, 2 cm–25 cm). There was no significant difference in patient age and tumor size between male and female. Major clinical presentations included abdominal pain or discomfort, and palpable abdominal masses, however, nearly one third of all patients were asymptomatic. The rate of pre‐operative misdiagnosis was rather high. Those who tested positive to metastases or invasions, 14.4% of the patients were diagnosed as malignant SPTs. Sex, age, symptoms, tumor size and tumor markers were not significant clinical factors to predict SPTs with malignant potential. Surgical procedures mainly included pancreatoduodenectomy, distal pancreatectomy and local resection. Three patients developed local recurrence, and one patient developed hepatic metastasis, all within four years after tumor resection. Five patients with malignant SPTs died due to tumor progression within 25 months after surgery.

Conclusions:  Surgical resection is the most effective means for curing this rare tumor. Despite metastasis, a good satisfactory effect could be achieved by surgical debulking. At least 4‐yearly follow‐up is mandatory for all patients undergoing surgical resection.
Gastric myoelectrical and motor abnormalities in children and adolescents with functional recurrent abdominal pain
Authors: Devanarayana Niranga M , De Silva DG Harendra , De Silva H Janaka
Published: August 2008

Background and Aims:  Recurrent abdominal pain is common among children and adolescents. The majority of the affected patients have no apparent cause for their symptoms. This study evaluated gastric myoelectrical activity and motility abnormalities in children and adolescents with functional recurrent abdominal pain.

Methods:  Forty‐two children with functional recurrent abdominal pain [19 (45.2%) males, mean 8 years, SD 3 years, 19 functional abdominal pain, 9 irritable bowel syndrome, 9 functional dyspepsia, 1 abdominal migraine, 1 aerophagia and 3 non‐specific abdominal pain according to Rome III criteria] and 20 healthy children [10 (50%) males, mean 9 years, SD 2.7 years] from the same geographical area underwent electrogastrography (EGG), and ultrasonographic assessment of gastric emptying rate and antral motility.

Results:  Average gastric emptying rate, amplitude of antral contractions and antral motility index were lower in patients (46.5%, 74.3% and 6.5 respectively) compared to controls (66.17%, 89% and 8.3 respectively) (P < 0.001). Gastric emptying rate had a negative correlation with scores obtained for severity of symptoms (r = −0.63, P < 0.0001). Postprandial dominant frequency instability co‐efficient (post‐DFIC) was higher in patients than in controls (27.83% vs 18.3%, P = 0.0087), and correlated with the symptom score (r = 0.26, P = 0.045).

Conclusions:  Gastric emptying and antral motility were significantly impaired in patients, indicating a possible role for gastric motility disturbances in the pathogenesis of childhood functional recurrent abdominal pain. Further studies, including therapeutic trials, are needed to confirm this association and for recommendation of prokinetic drugs in its management.
Nutritional rickets and z scores for height in the United Arab Emirates: To D or not to D?
Authors: Rajah Jaishen , Jubeh Jamal A. , Haq Afrozul , Shalash Amani , Parsons Howard
Published: August 2008

Background: Vitamin D deficiency is still prevalent worldwide, including the Middle East. A cohort of patients with nutritional rickets was treated with vitamin D2 (ergocalciferol) alone. After this intervention, patients were followed to document changes in z scores for height after treatment. The secondary aim was to determine the proportion of affected children who had vitamin D deficiency or calcium deficiency.

Methods: Z score for height was calculated as the difference between the observed value and the median value, divided by the SD of the population. Z scores were compared in patients before and after treatment.

Results: The improvement in z score after treatment was 0.86 ± 0.95. The 95% confidence interval for the mean difference was 1.32–0.40 (t = 3.95, P < 0.001). With a diagnostic cut‐off for 25 hydroxyvitamin D3 (25D) deficiency of <25 nmol/L, only half were diagnosed with severe vitamin D deficiency. The remaining patients had presumable calcium deficiency. The alkaline phosphatase (ALP) was negatively correlated to z scores, implying that higher ALP concentrations predicted severe bone disease (lower z scores). The variables 25D and age were moderately and positively correlated (Pearson’s r = 0.59, 95%CI: 0.15–0.84; P = 0.01), indicating that younger infants had the lowest 25D levels.

Conclusion: Vitamin D alone was efficient in resolving radiological and biochemical disturbances as well as improving z scores for height in a cohort of children with nutritional rickets, which included patients with 25D deficiency as well as calcium deficiency. The results support the hypothesis of the interplay and continuum of 25D deficiency and calcium deficiency in the pathogenesis of rickets.
Wheezing illness caused by respiratory syncytial virus and other agents
Authors: Yasuno Tetsuya , Shimizu Tsunehiro , Maeda Yosuke , Yamasaki Atsuko , Amaya Eriko , Kawakatsu Hidekazu
Published: August 2008

Background: Respiratory syncytial virus (RSV) and other pathogenic agents cause lower respiratory infection with wheezing in infants (wheezing illness in infancy). Wheezing illness in infancy due to RSV can be life‐threatening and can induce recurrent wheezing; but these events can also be produced by infection by other pathogenic agents. Thus, whether RSV induces more severe wheezing illness in infancy remains poorly understood.

Methods: Infants with an initial wheezing illness were divided into an RSV‐positive group and an RSV‐negative group and the differences in disease severity, intensity of acute symptoms, and susceptibility to recurrent wheezing, between these two groups, were investigated.

Results: The RSV‐positive group accounted for 57.4% of the infants. The infants in the RSV‐positive group were significantly younger than those in the RSV‐negative group. Other background parameters, gender and family history, were not significantly different. There were no significant differences in indicators of severity (hospitalization periods, periods of persistent wheezing and requirement of oxygen supplementation) between the two groups.

Conclusion: Wheezing illness in infancy caused by RSV is more common in younger infants, but it is not more severe than that caused by other pathogenic agents.
Internet survey of childhood asthma and use of inhaled therapy in the home in Japan
Authors: Yoshihara Shigemi , Yoshida Takami , Kurosaka Fumitake , Arisaka Osamu , Furusho Kenshi
Published: August 2008

Background: The aim of the present study is to undertake a survey of childhood asthma and details of the use of inhaled therapy from mothers with asthmatic children ≤15 years old, using the Internet.

Methods: This study was done on a nationwide scale in Japan during the latter half of July 2001.

Results: Responses were obtained from 748 mothers. Four hundred and three children (53.9%) had been diagnosed with asthma when ≤2 years old and 263 children (35.2%) when 2–5 years old. Three hundred and ninety‐seven children (53.1%) were in remission or had mild asthma, 295 children (39.4%) had moderate asthma, and 56 (7.5%) had severe asthma. Of 563 children who required some pharmacological treatment, 266 used inhaled therapy. One hundred and forty‐four children used metered‐dose inhaler (MDI), 136 used powered nebulizer, and 34 used dry powder inhaler (DPI). Of children treated with inhaled sodium cromoglycate, 63 used MDI, 129 used nebulizer solution and 23 used DPI. Of children treated with inhaled corticosteroids, 43 used MDI and six used DPI. Of children using powered nebulizer, 48 were well satisfied and 76 were slightly satisfied. More than 90% of mothers commented that this form of treatment improved the quality of life both of the asthmatic children and of the family.

Conclusion: Internet survey of childhood asthma is effective, and powered nebulizer therapy may be encouraged more acceptable by infants and young children in the treatment of asthma.
Gillies Lecture: Dissecting glaucoma: understanding the molecular risk factors
Authors: Mackey David A
Published: August 2008

Abstract

WE Gillies was a major contributor to research in glaucoma, notably pseuodexfoliation (XFS), as well as strabismus, particularly in relation to axial length (AL). The latter work involved breaking down the geometry of the eye to its basic components and using the measured AL to tailor the amount of strabismus surgery required. Similarly, the search for glaucoma genes requires us to break down glaucoma into its component measures and associated risk factors. Over the last 14 years, our data from the Glaucoma Inheritance Study in Tasmania have shown the following: that a family history is present in 60% of glaucoma cases; that 27% of members of large glaucoma families were unaware of their family history of glaucoma; and that familial glaucoma is more severe than sporadic glaucoma. Myocilin mutations account for 3% of cases of primary open angle glaucoma. Some genotype–phenotype correlations have been identified. Notably, with respect to earlier age of onset, higher maximum recorded intraocular pressure and need for surgery, the Gln368Stop mutation confers mild risk, Thr377Met and Gly252Arg mutations intermediate risk, and the Pro370Leu mutation severe risk. To identify the other genes associated with glaucoma, we have examined normal twins in the Twins Eye Study to determine the heritability of parameters that are abnormal in glaucoma – intraocular pressure and cup‐to‐disc ratio and confounding factors for glaucoma such as central corneal thickness, disc area, refraction and AL. We have identified high heritabilities for all of these as well as a gene locus associated with AL on chromosome 5. Recently, the LOXL1 gene was associated with XFS. Identification of further genes will improve our understanding of glaucoma and allow cascade genetic screening.