bluuebunny/crossref_metadata_2025 huggingface dataset:
Chickens possess centromeres with both extended tandem repeats and short non-tandem-repetitive sequences
Authors: Shang Wei-Hao , Hori Tetsuya , Toyoda Atsushi , Kato Jun , Popendorf Kris , Sakakibara Yasubumi , Fujiyama Asao , Fukagawa Tatsuo
Published: June 2010

The centromere is essential for faithful chromosome segregation by providing the site for kinetochore assembly. Although the role of the centromere is conserved throughout evolution, the DNA sequences associated with centromere regions are highly divergent among species and it remains to be determined how centromere DNA directs kinetochore formation. Despite the active use of chicken DT40 cells in studies of chromosome segregation, the sequence of the chicken centromere was unclear. Here, we performed a comprehensive analysis of chicken centromere DNA which revealed unique features of chicken centromeres compared with previously studied vertebrates. Centromere DNA sequences from the chicken macrochromosomes, with the exception of chromosome 5, contain chromosome-specific homogenous tandem repetitive arrays that span several hundred kilobases. In contrast, the centromeres of chromosomes 5, 27, and Z do not contain tandem repetitive sequences and span non-tandem-repetitive sequences of only ∼30 kb. To test the function of these centromere sequences, we conditionally removed the centromere from the Z chromosome using genetic engineering and have shown that that the non-tandem-repeat sequence of chromosome Z is a functional centromere.
Validation and efficacy of transgenerational mass marking of otoliths in viviparous fish larvae
Authors: Kuroki M. , Buckley R. M. , LeClair L. L. , Hauser L.
Published: June 2010

Transgenerational mass marking of viviparous fish larvae in vivo was validated by intra‐muscular injection of elemental strontium chloride (SrCl2) in gestating females and detection of the Sr in the otoliths of developing larvae. All otoliths of brown rockfish Sebastes auriculatus larvae produced from SrCl2‐injected females showed enriched Sr:Ca ratios near the otolith edges, and the signatures did not appear to be affected by the anterior, centre and posterior positions of larvae within the ovary. Results from the present study indicate that transgenerational marking is a highly reliable technique for marking large numbers of extremely small viviparous fish larvae.
Molecular cloning and localization of the luteinizing hormone β subunit and glycoprotein hormone α subunit from Japanese anchovy Engraulis japonicus
Authors: Ohkubo M. , Katayama S. , Shimizu A.
Published: June 2010

Although Clupeiformes contain many economically important species, there is limited information on their reproductive physiology. To obtain more insight into reproductive mechanisms in clupeiform fishes, molecular cloning of the Japanese anchovy Engraulis japonicus luteinizing hormone β (LHβ) and glycoprotein hormone α (GPHα) subunits, and immunocytochemistry of gonadotrophs in the pituitary using antisera raised against the synthetic peptides for both subunits were carried out. The cDNAs for LHβ and GPHα subunits consisted of 963 and 535 nucleotides encoding 141 and 122 amino acids, respectively. The deduced amino acid sequences of the E. japonicus LHβ subunit showed a 60% similarity to the Pacific herring Clupea pallasii LHβ subunit and 24–31% similarities to FSHβ subunits of other fish species. The E. japonicus GPHα subunit showed 52–57% similarities to anguilliform and cypriniform GPHα subunits. Both the subunits have typical structural characteristics of each subunit such as N‐linked glycosylation sites, conserved cysteine residues and highly conserved short amino acid sequences. These results indicate that cDNAs cloned in this study encode the E. japonicus LHβ and GPHα subunits. Reverse‐transcription polymerase chain reaction (RT‐PCR) revealed that both the LHβ and GPHα subunit genes were abundantly expressed in the pituitary, and the GPHα subunit was observed to be weakly expressed in the extrapituitary tissues. Immunocytochemistry of the E. japonicus pituitary showed that cells that immunoreacted with antiserum against the LHβ subunit were distributed in the peripheral regions of proximal pars distalis, and these cells were also immunoreactive to antiserum against the GPHα subunit. An abundant number of both LHβ and GPHα cells in the pituitary of matured fish were observed, in comparison with immature fish. These results indicate that the E. japonicus LH is involved in the final reproductive maturation as well as those of other teleosts.
Being the Older Sibling: Self‐Perceptions of Children with Disabilities
Authors: Serdity Clare , Burgman Imelda
Published: June 2010

This exploratory study explored the experience of being an older sibling, from the perspective of children with disabilities. A phenomenological approach was used to investigate the experiences of 10 children with disabilities. The participants described engagement in older sibling roles that they perceived to positively influence their sense of self. In most instances participants perceived family dynamics, gender and personality to be more influential on this engagement than their impairment. Children with disabilities engage in a diversity of roles as an older sibling. These roles need to be respected and built upon in family centred‐practice to enable children to fully contribute to family life.
Clinical impact of dose reductions and interruptions of second‐generation tyrosine kinase inhibitors in patients with chronic myeloid leukaemia
Authors: Santos Fabio P. S. , Kantarjian Hagop , Fava Carmen , O’Brien Susan , Garcia‐Manero Guillermo , Ravandi Farhad , Wierda William , Thomas Deborah , Shan Jianquin , Cortes Jorge
Published: June 2010

Second (2nd)‐generation tyrosine kinase inhibitors (TKI) (dasatinib, nilotinib) are effective in patients with all phases of chronic myeloid leukaemia (CML). Dose reductions and treatment interruptions are frequently required due to toxicity, but their significance is unknown. We analysed the impact of dose reductions/interruptions and dose intensity of 2nd‐generation TKI on response and survival. A total of 280 patients with CML (all phases) were analysed. Dose reductions were considered when the daily dose was below the standard dose. Dose intensity was determined based on the percentage of the ideal dose intensity. Overall, 176 patients (63%) required treatment interruptions and/or dose reduction at least once during therapy. Dose reductions/interruptions, analysed as a time‐dependent covariate, were associated with worse failure‐free survival only in patients with untreated CML. Dose intensity analysis did not reveal a worse response or survival in patients who received a lower dose intensity (<100%) during therapy or during the first 6 months. In conclusion, dose reductions and treatment interruptions of 2nd generation TKI in patients with CML have a minimal impact in the response rate and survival of these patients. Further studies are required to determine whether there might be a minimum adequate dose of these agents.
Pulmonary hypertension in sickle cell disease children under 10 years of age
Authors: Colombatti Raffaella , Maschietto Nicola , Varotto Elena , Grison Alessandra , Grazzina Nicoletta , Meneghello Linda , Teso Simone , Carli Modesto , Milanesi Ornella , Sainati Laura
Published: June 2010

Despite the finding of elevated Tricuspid Regurgitant Velocity (TRV) in children below 5 years of age, the prevalence and evolution of Pulmonary Hypertension (PH) in young children with sickle cell disease (SCD) are unclear. In order to identify predictive factors of precocious PH development, SCD children ≥3 years old, at steady state, underwent annual echocardiography and Tissue Doppler Imaging (TDI). Patients receiving chronic transfusion were excluded. Thirty‐seven of seventy‐five patients were ≥3 years, with measurable TRV. In our young population (mean age 6·2 years) of mainly African, HbS/HbS patients, 8/37 (21·6%) had TRV ≥2·5 m/s, 8% being only 3 years old. Significant correlation was found between precocious TRV elevation and high platelet and reticulocyte counts and frequent acute chest syndromes (ACS). In multivariate analysis, ACS was the only variable predicting TRV ≥2·5 m/s. TDI of the 37 patients showed signs of diastolic dysfunction of the left ventricle. At follow‐up all eight patients with high TRV displayed further increase and seven more developed TRV ≥2·5 m/s. PH seems to begin in children earlier than expected. Factors involved in its early onset might be different from the ones causing its development in older children or adults. African children might benefit from early screening and re‐assessment once a year.
Verification that common variation at 2q37.1, 6p25.3, 11q24.1, 15q23, and 19q13.32 influences chronic lymphocytic leukaemia risk
Authors: Crowther‐Swanepoel Dalemari , Mansouri Mahmoud , Enjuanes Anna , Vega Ana , Smedby Karin E. , Ruiz‐Ponte Clara , Jurlander Jesper , Juliusson Gunnar , Montserrat Emilio , Catovsky Daniel , Campo Elias , Carracedo Angel , Rosenquist Richard , Houlston Richard S.
Published: June 2010

A recent genome wide association study of chronic lymphocytic leukaemia (CLL) provided evidence that common variation at 2q13 (rs17483466), 2q37.1 (rs13397985), 6p25.3 (rs872071), 11q24.1 (rs735665), 15q23 (rs7176508) and 19q13.32 (rs11083846) affects CLL risk. To verify and further explore the relationship between these variants and CLL risk we genotyped case‐control datasets from Spain and Sweden (824 cases, 850 controls). Combined data provided statistically significant support for an association between genotypes at rs13397985, rs872071, rs735665, rs7176508 and rs11083846 and CLL risk. CLL risk increased with increasing numbers of risk alleles (Ptrend = 1·40 × 10−15), consistent with a polygenic model of disease susceptibility. These data validate the relationship between common variation and risk of CLL.
Immediate and dual response to nasal challenge with Dermatophagoides pteronyssinus in local allergic rhinitis
Authors: López S. , Rondón C. , Torres M. J. , Campo P. , Canto G. , Fernandez R. , Garcia R. , Martínez‐Cañavate A. , Blanca M.
Published: June 2010

Background
Local allergic rhinitis (LAR) is characterized by in situ production of specific IgE (sIgE) antibodies and a positive response to a nasal allergen provocation test (NAPT) in the absence of atopy.

Objective
The aim of this study was to investigate the immunological mechanisms involved in the immediate and late responses after nasal exposure to Dermatophagoides pteronyssinus (DP) in patients with LAR.

Methods
A total of 40 subjects with LAR to DP were studied and compared with 50 healthy controls. Immediate and late responses to NAPT‐DP were assessed using a visual analogue scale of nasal symptoms and acoustic rhinometry. Tryptase, ECP, total and sIgE‐DP were measured in the nasal lavage by immunoassay at baseline, 15 min, 1, 6 and 24 h after nasal challenge.

Results
NAPT‐DP was positive in all patients, with significant increases in tryptase (45%), ECP (65%) and sIgE‐DP (25%) (P<0.05). Sixty percent of the LAR patients presented an immediate response to NAPT‐DP and 40% a dual response. Immediate responders showed a fast release of tryptase with a peak at 15 min after NAPT‐DP, and a progressive increase in nasal ECP and sIgE‐DP from 1 to 24 h after challenge, with a peak at 24 h. Dual responders presented persistently higher levels of tryptase from 15 min to 6 h after challenge, and a similar pattern of nasal release of ECP and sIgE‐DP to immediate responders. There were no isolated late responders. NAPT‐DP was negative in all healthy controls, with no increases in tryptase, ECP, or total and sIgE‐DP in nasal secretions.

Conclusions
The results demonstrated the existence of immediate and dual responses to a NAPT with DP in LAR patients, with the local presence of sIgE and mast cell/eosinophil activation.

Cite this as: S. López, C. Rondón, M. J. Torres, P. Campo, G. Canto, R. Fernandez, R. Garcia, A. Martínez‐Cañavate and M. Blanca, Clinical & Experimental Allergy, 2010 (40) 1007–1014.
Allergen‐specific T cell responses to immunotherapy monitored by CD154 and intracellular cytokine expression
Authors: Campbell J. D. , Buchmann P. , Kesting S. , Cunningham C. R. , Coffman R. L. , Hessel E. M.
Published: June 2010

Background
A sensitive measurement of low numbers of intracellular cytokine‐expressing antigen‐specific T cells from peripheral blood mononuclear cells (PBMC) is possible using CD154 as a marker of recently activated T cells. This technique may have potential for monitoring peripheral blood T cell responses to immunotherapy.

Objective
To evaluate the applicability of this method for measuring changes in cytokine production by allergen‐specific T cells in a clinical trial setting.

Methods
Ex vivo ragweed‐specific CD154 and intracellular cytokine expression were evaluated using a subset of subjects in an environmental chamber study of allergic rhinitis immunotherapy. PBMC were collected and cryopreserved from Amb a 1‐immunostimulatory oligodeoxynucleotide conjugate (AIC)‐treated (n=17) and placebo‐treated (n=15) ragweed‐allergic subjects both after pre‐ and post‐treatment ragweed exposures. In vitro allergen‐stimulated CD3+CD4+CD154+ T cell intracellular IL‐4, IL‐5, IL‐13, and IFN‐γ expression were evaluated by flow cytometry.

Results
Compared with the T helper type 2 (Th2) cytokine expression measured after pre‐treatment ragweed exposures, placebo‐treated subjects demonstrated a significantly elevated ragweed‐ and Amb a 1‐specific T cell IL‐4 and IL‐13 co‐expression (P=0.005 and P=0.022, respectively) and a significantly elevated ragweed‐specific IL‐5 expression (P<0.001) following post‐treatment ragweed exposures. In contrast, AIC‐treated subjects demonstrated no increases in allergen‐specific Th2 cytokine expression following post‐treatment ragweed exposures. IFN‐γ expression remained low and un‐changed in both groups. Subject reported total nasal symptom scores demonstrated modest but significant correlations with Amb a 1‐ and ragweed‐stimulated intracellular Th2 cytokine responses.

Conclusion
Combined CD154 and intracellular cytokine staining in PBMC can be used to sensitively monitor changes in antigen‐specific T cell subset frequencies in clinical studies. Antigen‐specific cytokine expression moderately correlated with the reported levels of allergic symptoms.

Trial Registration NCT00537355

Cite this as: J. D. Campbell, P. Buchmann, S. Kesting, C. R. Cunningham, R. L. Coffman and E. M. Hessel, Clinical & Experimental Allergy, 2010 (40) 1025–1035.
Induction of insulin‐like growth factor‐I by interleukin‐17F in bronchial epithelial cells
Authors: Kawaguchi M. , Fujita J. , Kokubu F. , Ohara G. , Huang S.‐K. , Matsukura S. , Ishii Y. , Adachi M. , Satoh H. , Hizawa N.
Published: June 2010

Cite this as: M. Kawaguchi, J. Fujita, F. Kokubu, G. Ohara, S‐K Huang, S. Matsukura, Y. Ishii, M. Adachi, H. Satoh and N. Hizawa, Clinical & Experimental Allergy, 2010 (40) 1036–1043.

Background
Increased expression of IL‐17F has been noted in the airway of asthmatic patients, but its role in asthma has not been fully elucidated. Insulin‐like growth factor‐I (IGF‐I) is known to be involved in airway remodelling and inflammation, while its regulatory mechanisms remain to be defined.

Objective
To further clarify the biological function of IL‐17F, we investigated whether IL‐17F is able to regulate the expression of IGF‐I in bronchial epithelial cells.

Methods
Bronchial epithelial cells were stimulated with IL‐17F in the presence or absence of T‐helper type 2 cytokines. Various kinase inhibitors were added to the culture to identify the key signalling events leading to the expression of IGF‐I, in conjunction with the use of short interfering RNAs (siRNAs) targeting mitogen‐ and stress‐activated protein kinase (MSK) 1, p90 ribosomal S6 kinase (p90RSK), and cyclic AMP response element‐binding protein (CREB).

Results
IL‐17F significantly induced IGF‐I gene and protein expression, and co‐stimulation with IL‐4 and IL‐13 augmented its production. MAP kinase kinase (MEK) inhibitors and the Raf1 kinase inhibitor significantly inhibited IGF‐I production, and the combination of PD98059 and Raf1 kinase inhibitor showed further inhibition. Overexpression of Raf1 and Ras dominant‐negative mutants inhibited its expression. MSK1 inhibitors significantly blocked IL17F‐induced IGF‐I expression. Moreover, transfection of the siRNAs targeting MSK1, p90RSK, and CREB blocked its expression.

Conclusions
In bronchial epithelial cells, IL‐17F is able to induce the expression of IGF‐I via the Raf1–MEK1/2–ERK1/2–MSK1/p90RSK–CREB pathway in vitro.
Authentication of food allergen quality by physicochemical and immunological methods
Authors: Sancho A. I. , Hoffmann‐Sommergruber K. , Alessandri S. , Conti A. , Giuffrida M. G. , Shewry P. , Jensen B. M. , Skov P. , Vieths S.
Published: June 2010

Purified allergens are required to detect cross‐contamination with other allergenic foods and to understand allergen interaction with other components of the food matrix. Pure allergens are also used for the diagnosis and treatment of food allergies. For example, serological methods are being developed to improve the quality of diagnosis, and to reduce the need for food challenge tests. In addition, recombinant allergens are being evaluated as candidate vaccines for safe and efficacious specific immunotherapy. Pure allergens are indispensable as reference materials for the calibration and standardization of methods between different laboratories and operators for risk assessment in the food industry. Therefore, there is a need for well‐defined purified food allergens. In this context, a panel of 46 food allergens from plant and animal sources has been purified, from either the food sources or as recombinant forms, within the EU‐funded EuroPrevall project. These allergens have been characterized by a battery of diagnostic tests demonstrating that they constitute an authentic, well‐defined library of comparable quality. The review summarizes the applications, potentials and limitations of key techniques used for the characterization and authentication of these allergen preparations, with a special emphasis on protein purity and identity, folding, post‐translational modifications and immunochemical properties. One key area identified is the development of powerful analytical techniques, such as mass spectrometry and nuclear magnetic resonance, to improve the authentication of allergens for routine applications in allergy management.

Cite this as: A. I. Sancho, K. Hoffmann‐Sommergruber, S. Alessandri, A. Conti, M. G. Giuffrida, P. Shewry, B. M. Jensen, P. Skov and S. Vieths, Clinical & Experimental Allergy, 2010 (40) 973–986.
‘Entopy’: local allergy paradigm
Authors: Powe D. G. , Bonnin A. J. , Jones N. S.
Published: June 2010

Cite this as: D. G. Powe, A. J. Bonnin and N. S. Jones, Clinical & Experimental Allergy, 2010 (40) 987–997.

Allergy is defined as an immediate hypersensitivity type I immunological disease, which can be IgE or non‐IgE driven, and in the latter case may be antibody or cell mediated. Atopy is a term used to describe individuals with a genetic predisposition for developing IgE‐mediated allergic disease. But more recently, it has become evident that IgE‐mediated disease can occur in non‐atopic subjects. While it is now generally accepted that mucosal local IgE has a role in the expression of atopic allergic disease, the concept of ‘local allergy’ in non‐atopic subjects has been proposed, with the term ‘entopy’ given to this condition. Although there is increasing evidence supporting this paradigm, entopy is only applicable to a proportion of non‐atopic patients, suggesting that other disease mechanisms exist to explain non‐atopic disease. This review considers the evidence for local mucosal allergy in atopic and non‐atopic individuals with an emphasis on diseases affecting the upper airways and eye. Furthermore, the diagnosis, treatment and relationship between local allergy and conventional (systemic) allergy are discussed, and alternative disease mechanisms predominantly involving antibodies or their sub‐components (free light chain Igs) are postulated to explain the ‘entopy’ paradigm. This review is intended to provide an improved understanding of the mechanisms and causes of local mucosal hypersensitivity.
The role of cross‐reactive carbohydrate determinants in the diagnosis of occupational allergy
Authors: Quirce S. , Salcedo G.
Published: June 2010

Cite this as: S. Quirce and G. Salcedo, Clinical & Experimental Allergy, 2010 (40) 962–964.
A major shift in Daphnia genetic structure after the first ice‐free winter in a German reservoir
Authors: ZEIS B. , HORN W. , GIGENGACK U. , KOCH M. , PAUL R. J.
Published: June 2010

1. Climate warming may cause disruption of trophic linkages in aquatic ecosystems and lead to changes in abundance and genetic structure of zooplankton populations. We monitored the community of the Daphnia galeata‐hyalina hybrid complex in the Saidenbach Reservoir (Saxony, Germany) using allozyme electrophoresis for three consecutive years (2005–07), including one (2007) following an unusually warm winter that prevented the formation of ice cover for the first time in the history of the reservoir.

2. Genetic composition during the 2007 season differed substantially from the two preceding years that experienced the usual 3‐month ice period. Three abundance peaks in June, July and October 2007 were dominated by hybrids of Daphnia galeata x hyalina, whereas in the 2005 and 2006 seasons two peaks in June and September were dominated by Daphnia hyalina genotypes.

3. The genetic composition of the pool of diapausing eggs produced in autumn and the rate of change of genotype abundance during the following spring indicate recruitment of the D. hyalina subpopulation from ex‐ephippial animals during the spring population increase.

4. The differing potential to contribute to the overwintering animal pool or to the inoculum from diapausing eggs was confirmed by results from laboratory life‐table experiments. Daphnia galeata clones survived longer and produced parthenogenetic offspring under winter conditions, whereas D. hyalina clones showed a shorter lifespan and produced resting eggs.

5. Our results indicate a profound role of recruitment strategy in the observed shift in genetic composition. Increasing winter temperatures predicted in the context of climate change may thus favour overwintering animals, leading to an increase in the contribution of these genotypes to the population. Such microevolutionary processes may dampen possible seasonal mismatches between daphnid populations and their food or predator populations.
Inducible defences are a stabilizing factor for predator and prey populations: a field experiment
Authors: BOEING WIEBKE J. , RAMCHARAN CHARLES W.
Published: June 2010

1. Based on mathematical models, antipredator defence mechanisms are commonly believed to have stabilizing effects on communities. However, empirical data are still lacking.

2. We tested stabilizing effects of an inducible vertical migration defence in two Daphnia pulex clones in a 5‐week field enclosure experiment. A defended (migrated down into darker water layers in the presence of fish chemicals in both laboratory and field experiments) and non‐defended (no ability to react to fish chemicals) clone were directly exposed to fish predators and compared to control enclosures (no fish).

3. In the absence of planktivorous fish, both defended and non‐defended clones exhibited boom‐and‐bust dynamics, probably owing to over‐exploitation of the food source. Predation almost led to extinction of the non‐defended Daphnia clone during the experiment and the fish, deprived of food, lost weight. However, the population density of the defended clone was stable and it did not over‐exploit the algal food source, while there was a continuous supply of food to the fish, which consequently gained weight.

4. We conclude that both consumptive and non‐consumptive (also called non‐lethal or trait‐mediated) predator effects, coupled with prey defences, are key contributors to prey stability. This has a positive effect on both the predator and the food organism of the prey.
Casein kinase 2‐dependent phosphorylation of human Rad9 mediates the interaction between human Rad9‐Hus1‐Rad1 complex and TopBP1
Authors: Takeishi Yukimasa , Ohashi Eiji , Ogawa Kaori , Masai Hisao , Obuse Chikashi , Tsurimoto Toshiki
Published: June 2010

The checkpoint clamp Rad9‐Hus1‐Rad1 (9‐1‐1) is loaded by the Rad17–RFC complex onto chromatin after DNA damage and plays a key role in the ATR‐dependent checkpoint activation. Here, we demonstrate that in vitro casein kinase 2 (CK2) specifically interacts with human 9‐1‐1 and phosphorylates serines 341 and 387 (Ser‐341 and Ser‐387) in the C‐terminal tail of Rad9. Interestingly, phosphorylated Ser‐387 has previously been reported to be required for interacting with a checkpoint mediator TopBP1. Indeed, 9‐1‐1 purified from Escherichia coli and phosphorylated in vitro by CK2 physically interacts with TopBP1. Further analyses showed that phosphorylation at both serine residues occurs in vivo and is required for the efficient interaction with TopBP1 in vitro. Furthermore, when over‐expressed in HeLa cells, a mutant Rad9 harboring phospho‐deficient substitutions at both Ser‐341 and Ser‐387 residues causes hypersensitivity to UV and methyl methane sulfonate (MMS). Our observations suggest that CK2 plays a crucial role in the ATR‐dependent checkpoint pathway through its ability to phosphorylate Ser‐341 and Ser‐387 of the Rad9 subunit of the 9‐1‐1 complex.
Molecular characterization of 11 novel mutations in patients with heterozygous and homozygous FV deficiency
Authors: CUTLER J. A. , PATEL R. , RANGARAJAN S. , TAIT R. C. , MITCHELL M. J.
Published: June 2010

Summary.  Coagulation factor V (FV) has an important role in the blood coagulation cascade, in both the pro‐ and anticoagulant pathways. FV deficiency is a rare bleeding disorder with variable phenotypic expression. We report a cohort of 10 patients with mild‐severe FV deficiency in whom a total of 11 novel mutations were identified. Three patients were compound heterozygous for two mutations, whereas each of the remaining patients had a single heterozygous variant. FV levels did not correlate with either the type of mutation identified or the bleeding diathesis exhibited by the patients. Although considered to have an autosomal recessive mode of inheritance, patients with a single missense mutation may present with a significant bleeding history. The addition of a significant number of previously unidentified mutations to the public domain will contribute to the knowledge and understanding of the molecular pathology of this rare disorder.
Concept formation: a supportive process for early career nurses
Authors: Thornley Tracey , West Sandra
Published: June 2010

Background.  Individuals come to understand abstract constructs such as that of the ‘expert’ through the formation of concepts. Time and repeated opportunity for observation to support the generalisation and abstraction of the developing concept are essential if the concept is to form successfully. Development of an effective concept of the ‘expert nurse’ is critical for early career nurses who are attempting to integrate theory, values and beliefs as they develop their clinical practice.

Aim.  This study explores the use of a concept development framework in a grounded theory study of the ‘expert nurse’.

Design.  Qualitative.

Method.  Using grounded theory methods for data collection and analysis, semi‐structured interviews were conducted with registered nurses. The participants were asked to describe their concept of the ‘expert nurse’ and to discuss their experience of developing this.

Results.  Participants reported forming their concept of the ‘expert nurse’, after multiple opportunities to engage with nurses identified as ‘expert’. This identification did not necessarily relate to the designated position of the ‘expert nurse’ or assigned mentors. When the early career nurse does not successfully form a concept of the ‘expert nurse’, difficulties in personal and professional development including skill/knowledge development may arise.

Conclusion.  To underpin development of their clinical practice effectively, early career nurses need to be provided with opportunities that facilitate the purposive formation of their own concept of the ‘expert nurse’. Formation of this concept is not well supported by the common practice of assigning mentors.

Relevance to clinical practice.  Early career nurses must be provided with the time and the opportunity to individually develop and refine their concept of the ‘expert nurse’. To achieve this, strategies including providing opportunities to engage with expert nurses and discussion of the process of concept formation and its place in underpinning personal judgments may be of assistance.
Asia‐Pacific nursing scholarship development: qualitative exploration of nurse scholars in Taiwan (Republic of China)
Authors: Turale Sue , Shih Fu‐Jin , Klunklin Areewan , Chontawan Ratanawadee , Ito Misae , Nakao Fujiko
Published: June 2010

Aim.  From the perspective of scholars, to describe a contemporary view of the development, facilitators of and barriers to nursing scholarship in Taiwan, to enhance policy‐making about research, education and practise development.

Background.  Nursing scholarship in the Asia‐Pacific region is in different stages of development, depending on in‐country resources and socio‐economic conditions. Little is known about the facilitators or barriers to nursing scholarship in some of these countries, including Taiwan, where nursing education has changed considerably over the last decade.

Design.  A qualitative exploratory design.

Method.  The study used snowballing to identify scholars who underwent semi‐structured in‐depth interviews. These were digitally recorded, transcribed verbatim and subjected to content analysis.

Results.  Interviews were held with 12 scholars and six major themes arose: ‘fulfilling our missions’; ‘active research productivity’; ‘low levels of collaborative research’; ‘increasing demands on time’; ‘gender issues’ and ‘developing effective collaborative networks across Taiwan and Asia’. Participants described Taiwanese scholarship development in terms of fulfilling the missions of universities; trying to balance work and culturally relevant family responsibilities, against a background of decreasing pressures to produce more qualified nurses and being more research productive in rapidly changing and challenging work environments.

Conclusions.  Taiwan’s nursing scholarship is in a dynamic early stage of development, with increasing graduate programmes and research productivity, evidenced by rising international publications and the research productivity indexes of academics. However, scholars are facing increasing pressure because of high workloads and balancing family and work responsibilities.

Relevance to clinical practice.  Understanding scholarship development and its facilitators and barriers in Taiwan helps inform policy makers, the higher education sector and nurses in the country and across the region about what needs to be done to improve nursing practice, raise health outcomes and enhance nursing research productivity and education.
Effect of hospital on variation in visual acuity and vision‐specific quality of life after cataract surgery
Authors: Quintana Jose M. , Escobar Antonio , Bilbao Amaia , Navarro Gemma , Begiristain Jose M. , De Larrea Nerea Fernandez , Perea Emilio , Alberdi Txomin ,   the IRYSS Cataract Group
Published: June 2010

Objective  To evaluate the contribution of hospital‐to‐hospital variability in changes in clinical and health‐related quality of life outcomes among patients undergoing cataract extraction by phacoemulsification.

Methods  Prospective observational study of 14 public hospitals. We recruited consecutive patients on waiting lists for cataract extraction. Clinical data were collected prior to the intervention and 6 weeks afterward. Subjects completed the visual function index (VF‐14) prior to the procedure and 3 months afterward. Univariate and multivariate analysis were performed for visual acuity and VF‐14 scores.

Results  Substantial differences were observed across the 14 hospitals. At baseline, mean visual acuity ranged from 0.16 to 0.34, and mean VF‐14 scores ranged from 48.06 to 75.89. Following cataract extraction, the mean improvement in visual acuity ranged from 0.35 to 0.57 and in VF‐14 scores from 10.94 to 41.70. The ranges were even more pronounced among patients with low visual acuity or low VF‐14 scores prior to the intervention. Significant differences remained in multivariate analysis. Within the multivariate analysis, the variable ‘hospitals’ had an R2 of 0.069 for the visual acuity model and of 0.073 for the VF‐14 model, 20% and 13%, respectively, of the total variability explained. Variation was also observed within geographic regions.

Conclusions  Outcomes of patients undergoing cataract extractions vary widely from hospital to hospital, even within the same geographic region, explaining an important part of the results. Quality improvement efforts should concentrate on patients with low pre‐intervention visual acuity or vision‐related disability to reduce this variability in outcomes.
Impact of advanced exercise ECG analysis on cost of coronary artery disease management
Authors: Bigi Riccardo , Ferrando Alberto , Pagano Eva , Cortigiani Lauro , Merletti Franco , Fiorentini Cesare , Gregori Dario
Published: June 2010

Background  Conventional analysis of exercise electrocardiogram (EX‐ECG) has limited accuracy. This study aims to evaluate the potential impact of improving EX‐ECG accuracy on costs of diagnosis and number of misdiagnoses of coronary artery disease (CAD).

Methods  A decision‐tree model was simulated including sequential application of diagnostic procedures for suspected CAD. The model was structured in two main branches (presence or absence of CAD). A probabilistic sensitivity analysis was then performed for several combinations of improvement in test sensitivity and specificity.

Results  A clear trend in cost reduction was observed at improving EX‐ECG specificity (about 8–8.5 million dollars, corresponding to a 5.6–7.6% reduction according to the prevalence level). Wrong diagnoses counted for 9–13% of test. Improvements in test parameters lead to reductions in wrong diagnoses, especially when increasing specificity (8.8–12.5%).

Conclusions  A proper improvement in EX‐ECG sensitivity and specificity would have a relevant impact on the costs of CAD management, while reducing the number of misdiagnoses.
Comparing the quality of care across Belgian hospitals from medical basic datasets: the case of thromboembolism prophylaxis after major orthopaedic surgery
Authors: Gerkens Sophie , Crott Ralph , Closon Marie‐Christine , Horsmans Yves , Beguin Claire
Published: June 2010

Rationale, aims and objectives  In the current context, the assessment of the quality of care in daily clinical practice becomes essential. The aim of this study was to use medical basic datasets associated with information on pharmacological treatments to assess the quality of care of a prophylaxis treatment after major orthopaedic surgery and to compare hospitals' clinical practices.

Methods  The study was performed in 20 Belgian hospitals. Patients who underwent total hip replacement (THR), total knee replacement (TKR), or hip fracture surgery (HFS) were selected retrospectively from the hospitals' 2002 and 2003 administrative databases (n = 14 991). Quality indicators assessed were incidence of venous thromboembolism, major bleeding and death. Prophylaxis analysed were enoxaparin, nadroparin and fondaparinux.

Results  Venous thromboembolism and major bleeding events were rare (1.9% and 1.1% respectively). Patients who underwent HFS were at greater risk of having pulmonary embolism [OR = 2.01; confidence interval (CI) = 1.38–2.92; P = 0.0002], major bleeding (OR = 4.00; CI = 2.93–5.46; P < 0.0001) or death from any cause (OR = 8.86; CI = 6.85–11.45; P < 0.0001) than patients who underwent THR or TKR. Multivariate analyses showed that the hospital variable had a significant impact on the probability to have adverse events and that patients who received enoxaparin were at greater risk of death than patients who received nadroparin (ORenoxaparin vs fraxiparin = 1.59; 95% CI = 1.04–2.44; P = 0.033).

Conclusion  Results indicate that differences in thromboembolism prophylaxis practices among hospitals have a significant impact on adverse events. This reinforces the need to develop data‐processing tools that enable better monitoring of quality of care.
Rehabilitation services following total joint replacement: a qualitative analysis of key processes and structures to decrease length of stay and increase surgical volumes in Ontario, Canada
Authors: Fancott Carol , Jaglal Susan , Quan Victoria , Berg Katherine , Cott Cheryl A. , Davis Aileen , Flannery John , Hawker Gillian , Landry Michel D. , Mahomed Nizar N. , Badley Elizabeth
Published: June 2010

Objectives  The purpose of this study was: (1) to identify key total joint replacement (TJR) care processes and structures from acute care and rehabilitation hospitals; (2) to determine the perceived implications of practice patterns and processes on wait times, discharge planning, transitions in care, utilization of rehabilitation services, and outcomes; and (3) to understand how acute care hospitals funded for additional cases were addressing current and future rehabilitation needs.

Methods  A qualitative descriptive approach using key informant interviews was used to provide further insights and depth of understanding to current practice patterns, structures and processes of care for TJR patients.

Results  Twenty‐three key informants from a total of 15 hospitals across Ontario participated in this project. Themes that emerged related to processes of care (e.g. patient education, preoperative services, clinical pathways), and structures that supported these processes of care (e.g. organizational supports, increased funding and resources). The results point to a number of key practices that can facilitate smooth, integrated care for TJR patients, particularly in relation to best practices to decrease length of stay and increase surgical volumes. Increased funding related to strategic priorities placed on TJRs by the provincial government was viewed as an important impetus to implement a number of these key practices.

Conclusion  From a rehabilitation perspective, there is need for consistent funding to secure more rehabilitation services for both preoperative and post‐operative management of care that allows for shorter lengths of stay and to ensure optimal outcomes.
General practitioners' preferences for managing insomnia and opportunities for reducing hypnotic prescribing
Authors: Siriwardena A. Niroshan , Apekey Tanefa , Tilling Michelle , Dyas Jane V. , Middleton Hugh , Ørner Roderick
Published: June 2010

Rationale, aims and objectives Insomnia and sleep problems are common with many sufferers seeking medical help from general practitioners (GPs) whose clinical response is limited, often involving prescription of hypnotic drugs. The case for improving the quality of care for patients with insomnia is compelling but there is little evidence about how better care could be achieved in a primary care setting. The aim of this study was to investigate GPs' management preferences for sleep problems and their awareness and perception of opportunities for improving care as well as reducing the use of benzodiazepines and Z drugs.

Methods Cross‐sectional survey of GPs using a self‐administered postal questionnaire in 2005 to all GPs in West Lincolnshire Primary Care Trust Lincolnshire, UK.

Results A total of 84 of 107 (78.5%) questionnaires sent to GP principals were returned after one reminder. Respondents favoured Z drugs over benzodiazepines for the majority of indications. Respondent attitudes to benzodiazepines and Z drugs were generally negative whereas they were positive towards initiatives to reduce hypnotic prescribing through personal guidance, awareness‐raising strategies and organizational interventions.

Conclusions GPs were negative in attitude towards hypnotics and positive towards reducing prescribing for sleep problems. They need to develop resources and better strategies for assessment and non‐pharmacological management of patients presenting with insomnia for the first time as well as those on long‐term hypnotics. The feasibility and effectiveness of psychosocial interventions tailored to patient and service needs in primary care setting should be evaluated systematically seeking to understand potential clinical benefits as well as potential undesirable effects of service changes.
Comparison of the metabolic and economic consequences of long‐term treatment of schizophrenia using ziprasidone, olanzapine, quetiapine and risperidone in Canada: a cost‐effectiveness analysis
Authors: McIntyre Roger S. , Cragin Lael , Sorensen Sonja , Naci Huseyin , Baker Tim , Roussy Jean‐Pascal
Published: June 2010

Rationale, aims and objectives  Second‐generation antipsychotic agents have varying propensities to cause weight gain, elevated lipid levels and associated long‐term complications. This study evaluates the cost‐effectiveness of four second‐generation antipsychotic agents used in Canada for the treatment of schizophrenia (ziprasidone, olanzapine, quetiapine, risperidone) with a focus on their long‐term metabolic consequences.

Method  Using data from the Clinical Antipsychotic Trials of Intervention Effectiveness Study, a semi‐Markov model was developed to predict the incidence and associated costs of type 2 diabetes, cardiovascular complications (e.g. angina, myocardial infarction, stroke, cardiovascular disease death), and acute psychiatric hospitalizations in patients with chronic schizophrenia treated over 5 years. Incremental costs per quality‐adjusted life year (QALY) gained were calculated from the perspective of the Canadian provincial ministries of health. Scenario and probabilistic sensitivity analyses were performed.

Results  The total average cost of treatment with ziprasidone was $25 301 versus $28 563 with olanzapine, $26 233 with quetiapine and $21 831 with risperidone. Ziprasidone had the lowest predicted number of type 2 diabetes cases and cardiovascular disease events, and the highest QALY gains. Patients receiving quetiapine had the highest predicted number of hospitalizations. Ziprasidone was less costly and resulted in more QALYs compared with olanzapine and quetiapine. Compared with risperidone, ziprasidone was more costly and had higher QALYs, with an incremental cost per QALY gained of $218 060.

Conclusion  Compared with olanzapine and quetiapine, ziprasidone produced savings to the health care system. Although ziprasidone generated incremental expenditures versus risperidone, it resulted in more QALYs. Based on this analysis, ziprasidone treatment possesses cost and therapeutic advantages compared with olanzapine and quetiapine.
Sulfachlorpyrazine residues depletion in turkey edible tissues
Authors: ŁEBKOWSKA‐WIERUSZEWSKA B.I. , KOWALSKI C. J.
Published: June 2010

Łebkowska‐Wieruszewska, B.I., Kowalski, C.J. Sulfachlorpyrazine residues depletion in turkey edible tissues.J. vet. Pharmacol.Therap. doi: 10.1111/j.1365‐2885.2009.01147.x.

Sulfachlorpyrazine (SCP) is currently used to treat coccidian infections in turkeys; however, there is no information available about the withdrawal period necessary for the turkey to be safe for human consumption. A high performance liquid chromatography method with ultraviolet‐visible light detection was adapted and validated for the determination of SCP in turkey tissues. The procedure is based on isolation of the (SCP sodium) compound from edible turkey tissues (muscles, liver, kidneys, and fat with skin) with satisfactory recovery (72.80 ± 1.40) and specificity. The residue depletion of SCP in turkeys was conducted after a dose of 50 mg/kg body weight/day had been administrated orally for 3 days. After treatment has been discontinued residue concentrations were detected in tissues on the 7th day. The highest SCP concentrations were measured in muscles. Based on the results presented in this study, it could be assumed that a withdrawal period of 21 days, before medicated turkeys could be slaughtered, would be sufficient to ensure consumer safety.
Bioavailability and pharmacokinetics of metronidazole in fed and fasted horses
Authors: Britzi M. , Gross M. , Lavy E. , Soback S. , Steinman A.
Published: June 2010

Britzi, M., Gross, M., Lavy, E., Soback, S., Steinman, A. Bioavailability and pharmacokinetics of metronidazole in fed and fasted horses.J. vet. Pharmacol. Therap.33, 511–514.

Metronidazole (1‐[2‐hydroxyethyl]‐2‐methyl‐5‐nitroimidazole) is a bactericidal antimicrobial agent used for treatment of infectious diseases caused by anaerobic bacteria and protozoa. Pharmacokinetics of metronidazole following its administration to horses was previously described (Sweeneyet al., 1986;Baggotet al., 1988;Spechtet al., 1992;Steinmanet al., 2000). The bioavailability (F) was 85% (ranging from 57% to 105%) and the time to reach maximum serum concentration (tmax) was 1–2 h after oral dose at 25 mg/kg body weight (Sweeneyet al., 1986).Baggotet al.(1988)found thatFwas 74.5% (ranging from 58.4% to 91.5%) andtmaxwas 1.5 h after oral dose at 20 mg/kg body weight.Spechtet al.(1992)reported thatFwas 97% (ranging from 79% to 111%) andtmaxwas 40 min after oral dose at 15 mg/kg body weight. In an earlier study by our groupFwas 74% andtmaxwas 65 min after oral dose at 20 mg/kg body weight (Steinmanet al., 2000). These individual variations inFmight be partially explained by the effect of feed, among other factors, mainly on metronidazole absorption. Interactions between food and drugs may reduce or increase the drug effect. The majority of clinically relevant food–drug interactions are caused by food‐induced changes on the bioavailability of the drug (Schmidt & Dalhoff, 2002). In dogs, absorption of metronidazole is enhanced when given with food, but delayed in humans (Plumb, 1995). Although, metronidazole is used commonly to treat various clinical conditions in horses with relatively little adverse effects (Sweeneyet al., 1991), narrow margin of safety was suggested because histological evidence of peripheral neurotoxicity and hepatotoxicity were noted in horses treated with doses as low as 30 mg/kg body weight every 12 h orally for 30 days (Whiteet al., 1996). For drugs with a narrow therapeutic index, even small changes in dose–response effects can have significant consequences (Schmidt & Dalhoff, 2002).
The impact of HIV/HCV co‐infection on health care utilization and disability: results of the ACTG Longitudinal Linked Randomized Trials (ALLRT) Cohort
Authors: Linas B. P. , Wang B. , Smurzynski M. , Losina E. , Bosch R. J. , Schackman B. R. , Rong J. , Sax P. E. , Walensky R. P. , Schouten J. , Freedberg K. A.
Published: June 2010

Summary.  HIV/hepatitis C virus (HCV) co‐infection places a growing burden on the HIV/AIDS care delivery system. Evidence‐based estimates of health services utilization among HIV/HCV co‐infected patients can inform efficient planning. We analyzed data from the ACTG Longitudinal Linked Randomized Trials (ALLRT) cohort to estimate resource utilization and disability among HIV/HCV co‐infected patients and compare them to rates seen in HIV mono‐infected patients. The analysis included HIV‐infected subjects enrolled in the ALLRT cohort between 2000 and 2007 who had at least one CD4 count measured and completed at least one resource utilization data collection form (N = 3143). Primary outcomes included the relative risk of hospital nights, emergency department (ED) visits, and disability days for HIV/HCV co‐infected vs HIV mono‐infected subjects. When controlling for age, sex, race, history of AIDS‐defining events, current CD4 count and current HIV RNA, the relative risk of hospitalization, ED visits, and disability days for subjects with HIV/HCV co‐infection compared to those with HIV mono‐infection were 1.8 (95% CI: 1.3–2.5), 1.7 (95% CI: 1.4–2.1), and 1.6 (95% CI: 1.3–1.9) respectively. Programs serving HIV/HCV co‐infected patients can expect approximately 70% higher rates of utilization than expected from a similar cohort of HIV mono‐infected patients.