bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and economic impact of a specialty care management program among patients with multiple sclerosis: a cohort study
Authors: Tan H. , Yu J. , Tabby D. , Devries A. , Singer J.
Published: July 2010

Background: To evaluate the clinical and economic impact of a specialty care management program among patients with multiple sclerosis.

Methods: This retrospective cohort analysis included patients aged ≥18 years with ≥2 claims of multiple sclerosis diagnosis and ≥1 multiple sclerosis medications from 1 January 2004 to 30 April 2008. The outcome metrics included medication adherence and persistence, multiple sclerosis-related hospitalization, and multiple sclerosis-related cost. Multivariate analyses were performed to adjust for demographics and clinical characteristics.

Results: Among the 3993 patients identified, 78.3% participated in the program and 21.7% did not. Over 12 months, medication adherence and persistence improved among participants but deteriorated among non-participants (medication possession ratio change: +0.08 vs -0.03, p < 0.001; persistence change: +29.2 days vs -9.2 days, p < 0.001). Multiple sclerosis-related hospitalization decreased from 9.6% to 7.1% for participants, whereas it increased from 10.1% to 12.0% for the non-participant group ( p < 0.001). Multiple sclerosis-related medical spending (non-pharmacy) decreased among participants, but it increased among non-participants (mean: -US$264 vs + US$1536, p < 0.001). Total multiple sclerosis-related cost for both groups increased over time (+US$4471 vs +US$4087, p < 0.001).

Conclusions: This program was associated with improved medication adherence and persistence, reduced multiple sclerosis-related hospitalization, and decreased multiple sclerosis-related medical costs. Unfortunately, the cost savings in the medical component did not offset the increased pharmacy expenditures during the 12-month follow-up period.
Educational level is a crucial factor for good perceived health in the local community
Authors: Faresjö Tomas , Rahmqvist Mikael
Published: July 2010

Aims: Educational level is a strong determinant of perceived health, and also an important component in the socioeconomic concept. The aim of this study was to analyze a number of social conditions and lifestyle factors that might explain differences in self-reported health between the populations in two different social environments, one white-collar city and one blue-collar city. These ‘‘twin cities’’ are served by the same healthcare organisation, but differ in terms of social history and current social structure. Methods: The material consisted of responses to a community-based survey of individuals aged between 20 and 64 years, with an overall response rate of 49%. Differences in self-reported health status were tested with chi-square tests and regression analysis. Results: We found significant differences in perceived health between the two populations. These differences in self-reported health could not be explained by differences in demographic factors, lifestyles, or living conditions. However, when the educational level of the respondents was taken into account, the differences in perceived health diminished. Conclusions: Public health in local communities tends to reflect the social history and social heritage of the population. In this study, we found that educational level appears to be a vital factor for good perceived health of the individual in a community.
HLA genotyping in the international Type 1 Diabetes Genetics Consortium
Authors: Mychaleckyj Josyf C , Noble Janelle A , Moonsamy Priscilla V , Carlson Joyce A , Varney Michael D , Post Jeff , Helmberg Wolfgang , Pierce June J , Bonella Persia , Fear Anna Lisa , Lavant Eva , Louey Anthony , Boyle Sean , Lane Julie A , Sali Paul , Kim Samuel , Rappner Rebecca , Williams Dustin T , Perdue Letitia H , Reboussin David M , Tait Brian D , Akolkar Beena , Hilner Joan E , Steffes Michael W , Erlich Henry A ,   T1DGC
Published: July 2010

Background Although human leukocyte antigen (HLA) DQ and DR loci appear to confer the strongest genetic risk for type 1 diabetes, more detailed information is required for other loci within the HLA region to understand causality and stratify additional risk factors. The Type 1 Diabetes Genetics Consortium (T1DGC) study design included high-resolution genotyping of HLA-A, B, C, DRB1, DQ, and DP loci in all affected sibling pair and trio families, and cases and controls, recruited from four networks worldwide, for analysis with clinical phenotypes and immunological markers.

Purpose In this article, we present the operational strategy of training, classification, reporting, and quality control of HLA genotyping in four laboratories on three continents over nearly 5 years.

Methods Methods to standardize HLA genotyping at eight loci included: central training and initial certification testing; the use of uniform reagents, protocols, instrumentation, and software versions; an automated data transfer; and the use of standardized nomenclature and allele databases. We implemented a rigorous and consistent quality control process, reinforced by repeated workshops, yearly meetings, and telephone conferences.

Results A total of 15,246 samples have been HLA genotyped at eight loci to four-digit resolution; an additional 6797 samples have been HLA genotyped at two loci. The genotyping repeat rate decreased significantly over time, with an estimated unresolved Mendelian inconsistency rate of 0.21%. Annual quality control exercises tested 2192 genotypes (4384 alleles) and achieved 99.82% intra-laboratory and 99.68% inter-laboratory concordances.

Limitations The chosen genotyping platform was unable to distinguish many allele combinations, which would require further multiple stepwise testing to resolve. For these combinations, a standard allele assignment was agreed upon, allowing further analysis if required.

Conclusions High-resolution HLA genotyping can be performed in multiple laboratories using standard equipment, reagents, protocols, software, and

communication to produce consistent and reproducible data with minimal systematic error. Many of the strategies used in this study are generally applicable to other large multi-center studies. Clinical Trials 2010; 7: S75—S87. http:// ctj.sagepub.com
LEF-1 is a prosurvival factor in chronic lymphocytic leukemia and is expressed in the preleukemic state of monoclonal B-cell lymphocytosis
Authors: Gutierrez Albert , Tschumper Renee C. , Wu Xiaosheng , Shanafelt Tait D. , Eckel-Passow Jeanette , Huddleston Paul M. , Slager Susan L. , Kay Neil E. , Jelinek Diane F.
Published: July 2010

The canonical Wnt signaling pathway is pathogenic in a variety of cancers. We previously identified aberrant expression of the Wnt pathway transcription factor and target gene lymphoid enhancer binding factor-1 (LEF1) in chronic lymphocytic leukemia (CLL). This suggested that the Wnt signaling pathway has a role in the biology of CLL. In this study, we performed a Wnt pathway analysis using gene expression profiling and identified aberrant regulation of Wnt pathway target genes, ligands, and signaling members in CLL cells. Furthermore, we identified aberrant protein expression of LEF-1 specifically in CLL but not in normal mature B-cell subsets or after B-cell activation. Using the T cell–specific transcription factor/LEF (TCF/LEF) dual luciferase reporter assay, we demonstrated constitutive Wnt pathway activation in CLL, although the pathway was inactive in normal peripheral B cells. Importantly, LEF-1 knockdown decreased CLL B-cell survival. We also identified LEF-1 expression in CD19+/CD5+ cells obtained from patients with monoclonal B-cell lymphocytosis, suggesting a role for LEF-1 early in CLL leukemogenesis. This study has identified the constitutive activation and prosurvival function of LEF-1 and the Wnt pathway in CLL and uncovered a possible role for these factors in the preleukemic state of monoclonal B-cell lymphocytosis.
Screening for sleep-disordered breathing in neuromuscular disease using a questionnaire for symptoms associated with diaphragm paralysis
Authors: Steier J. , Jolley C.J. , Seymour J. , Teschler H. , Luo Y.M. , Polkey M.I. , Moxham J.
Published: July 2010

Patients with neuromuscular disease (NMD) are at risk of developing sleep-disordered breathing (SDB) following respiratory muscle involvement. We hypothesised that a questionnaire based on clinical symptoms and signs of diaphragm weakness can be used to screen for SDB in such patients.

We developed a self-administered multiple choice questionnaire containing five questions (Sleep-Disordered Breathing in Neuromuscular Disease Questionnaire (SiNQ)-5), scoring 0–10 points. 125 patients were enrolled: 32 with respiratory muscle weakness, 35 subjects with normal respiratory muscle strength and 58 patients with obstructive sleep apnoea (OSA). All subjects underwent full polysomnography.

NMD patients with involvement of the respiratory muscles scored mean±sd6.8±2.3 out of 10 points, significantly higher than both OSA patients 2.5±2.3 and normal subjects 1.0±2.0 (p<0.001). A score of five or more points in the SiNQ-5 had a sensitivity of 86.2%, specificity of 88.5%, positive predictive value of 69.4% and a negative predictive value of 95.5% to identify NMD with combined SDB.

A short self-administered questionnaire, the SiNQ-5, based on clinical symptoms can reliably screen for SDB in patients with diaphragm weakness. However, comorbidities, such as heart failure, that have symptoms influenced by posture could alter diagnostic accuracy.
Nasal inflammation in sleep apnoea patients using CPAP and effect of heated humidification
Authors: Koutsourelakis I. , Vagiakis E. , Perraki E. , Karatza M. , Magkou C. , Kopaka M. , Roussos C. , Zakynthinos S.
Published: July 2010

Nasal continuous positive airway pressure (CPAP) can cause undesirable nasal symptoms, such as congestion to obstructive sleep apnoea (OSA) patients, whose symptoms can be attenuated by the addition of heated humidification. However, neither the nature of nasal symptoms nor the effect of heated humidification on nasal pathophysiology and pathology are convincingly known.

20 patients with OSA on nasal CPAP who exhibited symptomatic nasal obstruction were randomised to receive either 3 weeks of CPAP treatment with heated humidification or 3 weeks of CPAP treatment with sham-heated humidification, followed by 3 weeks of the opposite treatment, respectively. Nasal symptom score, nasal resistance, nasal lavage interleukin-6, interleukin-12 and tumour necrosis factor-α and nasal mucosa histopathology were assessed at baseline and after each treatment arm.

Heated humidification in comparison with sham-heated humidification was associated with decrease in nasal symptomatology, resistance and lavage cytokines, and attenuation of inflammatory cell infiltration and fibrosis of the nasal mucosa.

In conclusion, nasal obstruction of OSA patients on CPAP treatment is inflammatory in origin and the addition of heated humidification decreases nasal resistance and mucosal inflammation.
Case fatality of COPD exacerbations: a meta-analysis and statistical modelling approach
Authors: Hoogendoorn M. , Hoogenveen R.T. , Rutten-van Mölken M.P. , Vestbo J. , Feenstra T.L.
Published: July 2010

The aim of our study was to estimate the case fatality of a severe exacerbation from long-term survival data presented in the literature.

A literature search identified studies reporting ≥1.5 yr survival after a severe chronic obstructive pulmonary disease (COPD) exacerbation resulting in hospitalisation. The survival curve of each study was divided into a critical and a stable period. Mortality during the stable period was then estimated by extrapolating the survival curve during the stable period back to the time of exacerbation onset. Case fatality was defined as the excess mortality that results from an exacerbation and was calculated as 1 minus the (backwardly) extrapolated survival during the stable period at the time of exacerbation onset. The 95% confidence intervals (CI) of the estimated case fatalities were obtained by bootstrapping. A random effect model was used to combine all estimates into a weighted average with 95% CI.

The meta-analysis based on six studies that fulfilled the inclusion criteria resulted in a weighted average case-fatality rate of 15.6% (95% CI 10.9–20.3), ranging from 11.4% to 19.0% for the individual studies.

A severe COPD exacerbation requiring hospitalisation not only results in higher mortality risks during hospitalisation, but also in the time-period after discharge and contributes substantially to total COPD mortality.
Underlying conditions in chronic pulmonary aspergillosis including simple aspergilloma
Authors: Smith N.L. , Denning D.W.
Published: July 2010

Chronic pulmonary aspergillosis (CPA) is a condition caused by the ubiquitous fungusAspergillus fumigatusin non-immunocompromised individuals. Numerous underlying conditions have been associated with CPA.

Details of the underlying conditions of 126 CPA patients attending our tertiary referral clinic from all over the UK were extracted from the clinical notes, and the distribution of these underlying conditions was analysed. For those with several underlying pulmonary conditions, one was nominated as the primary condition.

Many patients presented with multiple underlying conditions, and a total of 232 underlying conditions were identified for the 126 patients. Previous classical tuberculosis and non-tuberculous mycobacterial infection were the most common primary underlying conditions (15.3% and 14.9%, respectively). Others included allergic bronchopulmonary aspergillosis (ABPA), chronic obstructive pulmonary condition (COPD) and/or emphysema, pneumothorax and prior treated lung cancer. Some conditions were found more often as one of multiple underlying conditions, while others were found only as secondary underlying conditions.

Tuberculosis, non-tuberculous mycobacterial infection and ABPA remain the predominant risk factors for development of CPA, with COPD, prior pneumothorax or treated lung cancer also relatively common among our referrals. Many patients have multiple underlying pulmonary conditions. CPA should be considered when upper lobe cavitary or fibrotic disease and systemic symptoms are present in those with lung disease.
Procedure volume is one determinant of centre effect in mechanically ventilated patients
Authors: Darmon M. , Azoulay E. , Fulgencio J-P. , Garrigues B. , Gouzes C. , Moine P. , Villers D. , Teboul V. , le Gall J-R. , Chevret S.
Published: July 2010

Survival rates vary significantly between intensive care units, most notably in patients requiring mechanical ventilation (MV). The present study sought to estimate the effect of hospital MV volume on hospital mortality.

We included 179,197 consecutive patients who received mechanical ventilation in 294 hospitals. Multivariate logistic regression models with random intercepts were used to estimate the effect of annual MV volume in each hospital, adjusting for differences in severity of illness and case mix.

Median annual MV volume was 162 patients (interquartile range 99–282). Hospital mortality in MV patients was 31.4% overall, 40.8% in the lowest annual volume quartile and 28.2% in the highest quartile. After adjustment for severity of illness, age, diagnosis and organ failure, higher MV volume was associated with significantly lower hospital mortality among MV patients (OR 0.9985 per 10 additional patients, 95% CI 0.9978–0.9992; p = 0.0001). A significant centre effect on hospital mortality persisted after adjustment for volume effect (p<0.0001).

Our study demonstrated higher hospital MV volume to be independently associated with increased survival among MV patients. Significant differences in outcomes persisted between centres after adjustment for hospital MV volume, supporting a role for other significant determinants of the centre effect.
Brain metastases from lung cancer responding to erlotinib: the importance ofEGFRmutation
Authors: Porta R. , Sánchez-Torres J.M. , Paz-Ares L. , Massutí B. , Reguart N. , Mayo C. , Lianes P. , Queralt C. , Guillem V. , Salinas P. , Catot S. , Isla D. , Pradas A. , Gúrpide A. , de Castro J. , Polo E. , Puig T. , Tarón M. , Colomer R. , Rosell R.
Published: July 2010

Median survival of patients with brain metastases from nonsmall cell lung cancer (NSCLC) is poor and more effective treatments are urgently needed. We have evaluated the efficacy of erlotinib in this setting and its association with activating mutations in the epidermal growth factor receptor (EGFR) gene.

We retrospectively identified patients with NSCLC and brain metastases treated with erlotinib.EGFRmutations in exons 19 and 21 were analysed by direct sequencing. Efficacy and tolerability were compared according toEGFRmutational status.

69 NSCLC patients with brain metastases were identified, 17 of whom harbouredEGFRmutations. Objective response rate in patients withEGFRmutations was 82.4%; no responses were observed in unselected patients (p<0.001). Median (95% CI) time to progression within the brain for patients harbouringEGFRmutations was 11.7 (7.9–15.5) months, compared to 5.8 (5.2–6.4) months for control patients whoseEGFRmutational status had not been assessed (p<0.05). Overall survival was 12.9 (6.2–19.7) months and 3.1 (2.5–3.9) months (p<0.001), respectively. The toxicity of erlotinib was as expected and no differences between cohorts were observed.

Erlotinib is active in brain metastases from NSCLC; this clinical benefit is related to the presence of activating mutations in exons 19 or 21 of theEGFRgene.
Orthology confers intron position conservation
Authors: Henricson Anna , Forslund Kristoffer , Sonnhammer Erik LL
Published: July 2010

Background

With the wealth of genomic data available it has become increasingly important to assign putative protein function through functional transfer between orthologs. Therefore, correct elucidation of the evolutionary relationships among genes is a critical task, and attempts should be made to further improve the phylogenetic inference by adding relevant discriminating features. It has been shown that introns can maintain their position over long evolutionary timescales. For this reason, it could be possible to use conservation of intron positions as a discriminating factor when assigning orthology. Therefore, we wanted to investigate whether orthologs have a higher degree of intron position conservation (IPC) compared to non-orthologous sequences that are equally similar in sequence.

Results

To this end, we developed a new score for IPC and applied it to ortholog groups between human and six other species. For comparison, we also gathered the closest non-orthologs, meaning sequences close in sequence space, yet falling just outside the ortholog cluster. We found that ortholog-ortholog gene pairs on average have a significantly higher degree of IPC compared to ortholog-closest non-ortholog pairs. Also pairs of inparalogs were found to have a higher IPC score than inparalog-closest non-inparalog pairs. We verified that these differences can not simply be attributed to the generally higher sequence identity of the ortholog-ortholog and the inparalog-inparalog pairs.

Furthermore, we analyzed the agreement between IPC score and the ortholog score assigned by the InParanoid algorithm, and found that it was consistently high for all species comparisons. In a minority of cases, the IPC and InParanoid score ranked inparalogs differently. These represent cases where sequence and intron position divergence are discordant. We further analyzed the discordant clusters to identify any possible preference for protein functions by looking for enriched GO terms and Pfam protein domains. They were enriched for functions important for multicellularity, which implies a connection between shifts in intronic structure and the origin of multicellularity.

Conclusions

We conclude that orthologous genes tend to have more conserved intron positions compared to non-orthologous genes. As a consequence, our IPC score is useful as an additional discriminating factor when assigning orthology.
Plant microRNAs and their role in defense against viruses: a bioinformatics approach
Authors: Pérez-Quintero Álvaro L , Neme Rafik , Zapata Andrés , López Camilo
Published: July 2010

Background

microRNAs (miRNAs) are non-coding short RNAs that regulate gene expression in eukaryotes by translational inhibition or cleavage of complementary mRNAs. In plants, miRNAs are known to target mostly transcription factors and are implicated in diverse aspects of plant growth and development. A role has been suggested for the miRNA pathway in antiviral defense in plants. In this work, a bioinformatics approach was taken to test whether plant miRNAs from six species could have antiviral activity by targeting the genomes of plant infecting viruses.

Results

All plants showed a repertoire of miRNAs with potential for targeting viral genomes. The viruses were targeted by abundant and conserved miRNA families in regions coding for cylindrical inclusion proteins, capsid proteins, and nuclear inclusion body proteins. The parameters for our predicted miRNA:target pairings in the viral genomes were similar to those for validated targets in the plant genomes, indicating that our predicted pairings might behave in-vivo as natural miRNa-target pairings. Our screening was compared with negative controls comprising randomly generated miRNAs, animal miRNAs, and genomes of animal-infecting viruses. We found that plant miRNAs target plant viruses more efficiently than any other sequences, but also, miRNAs can either preferentially target plant-infecting viruses or target any virus without preference.

Conclusions

Our results show a strong potential for antiviral activity of plant miRNAs and suggest that the miRNA pathway may be a support mechanism to the siRNA pathway in antiviral defense.
Development and validation of self-reported line drawings for assessment of knee malalignment and foot rotation: a cross-sectional comparative study
Authors: Ingham Sarah L , Moody Amanda , Abhishek Abhishek , Doherty Sally A , Zhang Weiya , Doherty Michael
Published: July 2010

Background

For large scale epidemiological studies clinical assessments and radiographs can be impractical and expensive to apply to more than just a sample of the population examined. The study objectives were to develop and validate two novel instruments for self-reported knee malalignment and foot rotation suitable for use in questionnaire studies of knee pain and osteoarthritis.

Methods

Two sets of line drawings were developed using similar methodology. Each instrument consisted of an explanatory question followed by a set of drawings showing straight alignment, then two each at 7.5° angulation and 15° angulation in the varus/valgus (knee) and inward/outward (foot) directions. Forty one participants undertaking a community study completed the instruments on two occasions. Participants were assessed once by a blinded expert clinical observer with demonstrated excellent reproducibility. Validity was assessed by sensitivity, specificity and likelihood ratio (LR) using the observer as the reference standard. Reliability was assessed using weighted kappa (κ). Knee malalignment was measured on 400 knee radiographs. General linear model was used to assess for the presence of a linear increase in knee alignment angle (measured medially) from self-reported severe varus to mild varus, straight, mild valgus and severe valgus deformity.

Results

Observer reproducibility (κ) was 0.89 and 0.81 for the knee malalignment and foot rotation instruments respectively. Self-reported participant reproducibility was also good for the knee (κ 0.73) and foot (κ 0.87) instruments. Validity was excellent for the knee malalignment instrument, with a sensitivity of 0.74 (95%CI 0.54, 0.93) and specificity of 0.97 (95%CI 0.94, 1.00). Similarly the foot rotation instrument was also found to have high sensitivity (0.92, 95%CI 0.83, 1.01) and specificity (0.96, 95%CI 0.93, 1.00). The knee alignment angle increased progressively from self reported severe varus to mild varus, straight, mild valgus and severe valgus knee malalignment (ptrend <0.001).

Conclusions

The two novel instruments appear to provide a valid and reliable assessment of self-reported knee malalignment and foot rotation, and may have a practical use in epidemiological studies.
Solution structure of the human signaling protein RACK1
Authors: Gonçalves Kaliandra A , Borges Julio C , Silva Julio C , Papa Priscila F , Bressan Gustavo C , Torriani Iris L , Kobarg Jörg
Published: July 2010

Background

The adaptor protein RACK1 (receptor of activated kinase 1) was originally identified as an anchoring protein for protein kinase C. RACK1 is a 36 kDa protein, and is composed of seven WD repeats which mediate its protein-protein interactions. RACK1 is ubiquitously expressed and has been implicated in diverse cellular processes involving: protein translation regulation, neuropathological processes, cellular stress, and tissue development.

Results

In this study we performed a biophysical analysis of human RACK1 with the aim of obtaining low resolution structural information. Small angle X-ray scattering (SAXS) experiments demonstrated that human RACK1 is globular and monomeric in solution and its low resolution structure is strikingly similar to that of an homology model previously calculated by us and to the crystallographic structure of RACK1 isoform A from Arabidopsis thaliana. Both sedimentation velocity and sedimentation equilibrium analytical ultracentrifugation techniques showed that RACK1 is predominantly a monomer of around 37 kDa in solution, but also presents small amounts of oligomeric species. Moreover, hydrodynamic data suggested that RACK1 has a slightly asymmetric shape. The interaction of RACK1 and Ki-1/57 was tested by sedimentation equilibrium. The results suggested that the association between RACK1 and Ki-1/57(122-413) follows a stoichiometry of 1:1. The binding constant (KB) observed for RACK1-Ki-1/57(122-413) interaction was of around (1.5 ± 0.2) × 106 M-1 and resulted in a dissociation constant (KD) of (0.7 ± 0.1) × 10-6 M. Moreover, the fluorescence data also suggests that the interaction may occur in a cooperative fashion.

Conclusion

Our SAXS and analytical ultracentrifugation experiments indicated that RACK1 is predominantly a monomer in solution. RACK1 and Ki-1/57(122-413) interact strongly under the tested conditions.
A statistical model for mapping morphological shape
Authors: Fu Guifang , Berg Arthur , Das Kiranmoy , LI Jiahan , LI Runze , Wu Rongling
Published: July 2010

Background

Living things come in all shapes and sizes, from bacteria, plants, and animals to humans. Knowledge about the genetic mechanisms for biological shape has far-reaching implications for a range spectrum of scientific disciplines including anthropology, agriculture, developmental biology, evolution and biomedicine.

Results

We derived a statistical model for mapping specific genes or quantitative trait loci (QTLs) that control morphological shape. The model was formulated within the mixture framework, in which different types of shape are thought to result from genotypic discrepancies at a QTL. The EM algorithm was implemented to estimate QTL genotype-specific shapes based on a shape correspondence analysis. Computer simulation was used to investigate the statistical property of the model.

Conclusion

By identifying specific QTLs for morphological shape, the model developed will help to ask, disseminate and address many major integrative biological and genetic questions and challenges in the genetic control of biological shape and function.
A novel COMMD1 mutation Thr174Met associated with elevated urinary copper and signs of enhanced apoptotic cell death in a Wilson Disease patient
Authors: Gupta Arnab , Chattopadhyay Ishita , Mukherjee Shashwata , Sengupta Mainak , Das Shyamal K , Ray Kunal
Published: July 2010

Wilson disease (WD) results from accumulation of copper and caused due to mutations in ATP7B, a copper transporting ATPase. Besides regular hepatic and neurological symptoms, WD patients occasionally manifest atypical symptoms due to unknown cause. To understand the molecular etiology of atypical WD manifestations, we screenedCOMMD1, a gene implicated in canine copper toxicosis, in 109 WD patients including those with atypical symptoms. In a patient showing apoptotic symptoms and high urinary copper surpassing normal WD levels, we identified a novel, putative mutation inCOMMD1. Two other changes were also identified in the gene. We have examined genotype-phenotype correlation between the detected changes and the atypical presentation of the WD patient.
A novel, rapidly acquired and persistent spatial memory task that induces immediate early gene expression
Authors: Feldman Lisa A , Shapiro Matthew L , Nalbantoglu Josephine
Published: July 2010

Background

The Morris water maze task is a hippocampus-dependent learning and memory test that typically takes between 3 days to 2 weeks of training. This task is used to assess spatial learning and induces the expression of genes known to be crucial to learning and memory in the hippocampus. A major caveat in the protocol is the prolonged duration of training, and difficulty of assessing the time during training in which animals have learned the task. We introduce here a condensed version of the task that like traditional water maze tasks, creates lasting hippocampus-dependent spatial cognitive maps and elicits gene expression following learning.

Methods

This paradigm was designed for rats to quickly acquire a hippocampus-dependent spatial cognitive map and retain this memory for at least 24 hours. To accomplish this, we interspersed visible and hidden training trials, delivering them in a massed fashion so training takes a maximum of 15 minutes. Learning was assessed based on latencies to the platform during each training trial, as well as time spent in the goal quadrant during probe testing 30 minutes and 24 hours after training. Normal rats were compared to two impaired cohorts (rats with fimbria-fornix lesions and rats administered NMDA receptor antagonist (CPP)). To quantitate hippocampal expression of known learning genes, real-time polymerase chain reaction (RT-PCR) was performed on hippocampal cDNA.

Results

We show that massed training using alternating visible and hidden training trials generates robust short-term working and long-term reference memories in rats. Like the traditional Morris water maze paradigm, this task requires proper hippocampal function, as rats with fimbria-fornix lesions and rats administered CPP fail to learn the spatial component of the task. Furthermore, training in this paradigm elicits hippocampal expression of genes upregulated following learning in a variety of spatial tasks: homer1a, cfos and zif268.

Conclusions

We introduce here a condensed version of the Morris water maze, which is like a traditional water maze paradigm, in that it is hippocampus-dependent, and elicits hippocampal expression of learning genes. However, this task is administered in 15 minutes and induces spatial memory for at least 24 hours.
Postprandial plasma bile acid responses in normal weight and obese subjects
Authors: Glicksman C , Pournaras D J , Wright M , Roberts R , Mahon D , Welbourn R , Sherwood R , Alaghband-Zadeh J , le Roux C W
Published: July 2010

Background

Bile acids can act as signalling molecules via various receptors including the nuclear farnesoid X receptor (FXR) and pregnane X receptor (PXR), and the cell surface G-protein-coupled receptor TGR5. The signalling has been implicated in the release of peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), which improves glycaemic control and energy expenditure. We investigated whether morbidly obese subjects have altered postprandial bile acid responses in comparison to normal weight subjects.

Method

Blood samples were taken every 30 min from 0 to 180 min following a 400 kcal test meal. Samples were taken from 12 normal weight subjects with a body mass index (BMI) of 23.2 (2.8) kg/m2 (median [interquartile range (IQR)]) and seven obese patients with a BMI of 47.2 (7.2) kg/m2. Fractionated bile acids were measured on these samples using high-performance liquid chromatography tandem mass spectrometry.

Results

The obese subjects showed a lower postprandial response in total bile acids compared with the normal weight subjects. An increase of 6.4 (5.0) and 2.6 (3.3) μmol/L (median [IQR]) in normal weight and obese subjects was observed, respectively ( P = 0.02). The difference was predominantly due to the glycine-conjugated fraction ( P = 0.03). There was no difference in the increase of the unconjugated or taurine-conjugated fractions.

Conclusions

The decreased postprandial bile acid response in obese subjects compared with normal weight subjects may partly explain the suboptimal GLP-1 and PYY responses and could affect appetite, glycaemic control and energy expenditure.
Biochemical analysis of ascitic (peritoneal) fluid: what should we measure?
Authors: Tarn A C , Lapworth R
Published: July 2010

Ascitic fluid samples are frequently sent to the laboratory for analysis. Although the underlying cause of the ascites is often thought to be clinically obvious, it is important to establish a definitive diagnosis. The value of a cell count and bacterial culture of the ascitic fluid is not disputed, but the role of biochemical testing is less clear. The use of ascitic fluid total protein to try to classify ascitic fluids as either an exudate or a transudate has contributed to this. The use of the physiologically based serum ascites albumin gradient to differentiate ascites caused by portal hypertension from other causes provides a better diagnostic approach. We recommend that the serum ascites albumin gradient is performed by laboratories as the first-line test and that interpretative reports are provided. Additional testing should be restricted to specific diagnostic queries and requires close collaboration between the laboratory and the clinician.
Expressing thiopurineS-methyltransferase activity as units per litre of whole-blood overcomes misleading high results in patients with anaemia
Authors: Barlow N L , Graham V , Berg J D
Published: July 2010

Background

Thiopurine S-methyltransferase (TPMT) phenotype analysis, expressed as TPMT activity, is established as a routine pharmacogenomic test to screen patients prior to initiating thiopurine drug therapy. Conventionally measured TPMT activity is corrected for red blood cell (RBC) parameters. Here we present evidence that supports the simplification of the TPMT assay: by expressing TPMT activity in mU/L whole blood, without undertaking any haemoglobin (Hb) correction.

Methods

Hb concentrations were compared in consecutive samples that had been received for TPMT phenotype analysis and which were stratified into samples with high ( n = 111) and samples with normal ( n = 50) Hb-corrected enzyme activity. TPMT activity was also measured in samples received for full blood count determination, stratified into those with low ( n = 50) and normal ( n = 50) Hb. A reference interval for TPMT activity in mU/L was derived from a correlation between activity expressed in conventional units and that expressed in mU/L ( n = 1563), supported by comparison with associated genotype ( n = 201).

Results

In the high TPMT activity group, 83% of specimens had a low Hb concentration compared with 14% of specimens in the normal TPMT group. Samples with a low Hb concentration were found to have significantly higher Hb-corrected TPMT activity than samples with a normal Hb concentration: 83 versus 44 nmol 6-methyl thioguanine /g Hb/h, P < 0.0001. These results strongly suggest that misleading high Hb-corrected TPMT activity is found in anaemic patients. Based on the reference interval for enzyme activity of 70–150 mU/L, phenotype–genotype concordance compared well with the conventional approach (88% versus 89%). Furthermore, distribution of TPMT phenotypes with activity expressed in mU/L was identical: 0.5% deficient, 11% low, 86% normal and 2.5% high, to when it was expressed in conventional units.

Conclusion

Expressing TPMT activity in mU/L can overcome misleading high Hb-corrected TPMT results occurring in patients with anaemia, which could lead to inappropriate treatment. Removing the need to measure RBC indices further simplifies TPMT phenotyping, leading to a more robust assay, with reduced turn-around time and cost.
Tackling Multiplicity of Equilibria with Gröbner Bases
Authors: Kubler Felix , Schmedders Karl
Published: July 2010

Multiplicity of equilibria is a prevalent problem in many economic models. Often equilibria are characterized as solutions to a system of polynomial equations. This paper gives an introduction to the application of Gröbner bases for finding all solutions of a polynomial system. The Shape Lemma, a key result from algebraic geometry, states under mild assumptions that a given equilibrium system has the same solution set as a much simpler triangular system. Essentially, the computation of all solutions then reduces to finding all roots of a single polynomial in a single unknown. The software package Singular computes the equivalent simple system. If all coefficients in the original equilibrium equations are rational numbers or parameters, then the Gröbner basis computations of Singular are exact. Thus, Gröbner basis methods cannot only be used for a numerical approximation of equilibria, but in fact may allow the proof of theoretical results for the underlying economic model. Three economic applications illustrate that without much prior knowledge of algebraic geometry, Gröbner basis methods can be easily applied to gain interesting insights into many modern economic models.
Option Pricing Under GARCH Processes Using PDE Methods
Authors: Breton Michèle , Frutos Javier de
Published: July 2010

In this paper, we propose a partial differential equation formulation for the value of an option when the underlying asset price is described by a discrete-time GARCH process. Our numerical approach involves a spectral Fourier-Chebyshev interpolation. Numerical illustrations are provided, and the results are compared with other available valuation methods. Our numerical procedure converges exponentially fast and allows for the efficient computation of option prices, achieving a high level of precision in a few seconds of computing time.
The Prevalence of Dental, Facial and Head Injuries Sustained by Schoolboy Rugby Players. A Pilot Study
Authors: Jagger Robert G , Abbasbhai Ali , Patel Dilan , Jagger Daryll C , Griffiths Alex
Published: July 2010

Aim

The aim of the study was to determine the prevalence of dental, orofacial and head injuries and of mouthguard use among schoolboy rugby players.

Materials and methods

All members of the first and second XV rugby squads at three secondary schools (two in England and one in Australia) were included in the study. All participants answered a questionnaire that sought information regarding dental, orofacial and head injuries. Statistical differences between groups were determined using chi-square tests for categorical variables and Kruskal-Wallis tests for discrete (count) variables.

Results

One hundred and seventy-eight completed questionnaires were returned (100% response rate). One hundred and twenty-five (70%) players reported having sustained at least one injury (range 1–4). Facial injuries were common. Dental injuries were the most prevalent injury: 46 (26%) were reported. Fractured teeth were reported by 20 (11%) players, and avulsed teeth by 7 (4%). There was evidence of a difference between schools in the prevalence of injured players ( P=0.014), but among those reporting injuries, there was no difference between schools in the number of injuries ( P=0.95). All players said that they used a mouthguard regularly.

Conclusions

Dental, orofacial and head injuries were commonly reported. Dental injuries were the most prevalent type of injury. All players used mouthguards regularly.
Silver Scalpel: Awarding Outstanding Teaching and Training
Authors: Casey Heather
Published: July 2010

Ramez Kirollos, a consultant neurosurgeon from Cambridge, has taken the title of surgical trainer of the year as he picks up the Silver Scalpel award for 2010. Now in its tenth year, the Silver Scalpel is organised, funded and awarded by the Association of Surgeons in Training (ASiT) to recognise excellence in surgical training. It is awarded annually to inspirational trainers who have scored highly across five categories: leadership, resourcefulness, training and development, professionalism, and communication. In March this year, Mr Kirollos was presented with the award.
To Err is Human, to Cover up is Unforgivable
Authors: Towell Elaine
Published: July 2010

Medical history is punctuated with scandals in which things have gone wrong and have been covered up, from the Bristol heart scandal in the 1990s to the most recent example at Mid Staffordshire last year. More NHS doctors than ever before are coming into contact with the General Medical Council (GMC). Latest figures from the GMC show that the number of doctors subject to an enquiry increased by 11% in the period 2008–2009, with a rise of 30% of cases appearing in front of interim order panels. If you are a male doctor aged 40 or over you should probably keep reading this article…
Effect of Hard Water and Ammonium Sulfate on Weak Acid Herbicide Activity
Authors: Zollinger Richard K. , Nalewaja John D. , Peterson Dallas E. , Young Bryan G.
Published: July 2010

Glyphosate is a weak acid herbicide and can bind with calcium in the spray carrier. Diammonium sulfate is commonly used as an adjuvant with glyphosate to enhance phytotoxicity and overcome antagonistic effect of these cations. Most postemergence herbicides are also weak acid herbicides. Data is limited for other weak acid herbicides and the effect of diammonium sulfate in enhancing herbicide activity and overcoming antagonism. Field studies were conducted with aminopyralid, tembotrione, dicamba plus diflufenzopyr, and glufosinate to determine if (1) these weak acid herbicides are enhanced by ammonium, (2) if they are antagonized by calcium and magnesium in the spray solution, (3) if diammonium sulfate overcomes salt antagonism, and (4) if a previously published equation for the amount of ammonium sulfate required to overcome salt antagonism of glyphosate based on cation concentration in spray water correctly predicts to other weak acid herbicides. The activity of the four weak acid herbicides increased with the addition of ammonium to the spray solution, all were antagonized by calcium and magnesium, and diammonium sulfate overcame the antagonism. The previously published equation to calculate the amount the diammonium sulfate needed to overcome 500 and 1000 ppm hardness was accurate and can be used for these herbicides and possibly other weak acid herbicides.
Job Stress and Carotid Intima‐media Thickness in Chinese Workers
Authors: Xu Weixian , Hang Juan , Cao Tingting , Shi Rong , Zeng Wenshuang , Deng Yuanfei , Gao Wei , Zhao Yiming , Guo Lijun
Published: July 2010

Job Stress and Carotid Intima‐media Thickness in Chinese Workers: Weixian Xu, et al. Department of Cardiology, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, China

Objectives

Carotid intima‐media thickness (CIMT) can be used as a surrogate marker for cardiovascular health, and job stress is a risk factor for cardiovascular disease. However, there have been a limited number of studies focusing on the association between job stress and CIMT. The goal of this study was to explore the association between job stress and CIMT in a Chinese working population.

Methods

The study included 734 participants (508 males and 226 females) without coronary heart disease. Job stress was evaluated using the effort‐reward imbalance (ERI) questionnaire at work. ERI is the ratio between efforts and rewards (weighted by number of items). High resolution carotid ultrasonographic studies were performed using a Sequoia 512 ultrasound system with an 8–13 MHz linear array transducer to assess CIMT.

Results

This study detected gender‐specific associations between the indictors of the ERI model and increased CIMT among the study participants in China. This study demonstrated a robust association in women between the key indicators of ERI, effort, overcommitment and ERI, and increased CIMT (adjusted r2=0.258, p=0.001; adjusted r2=0.261; p<0.001; adjusted r2=0.274; p<0.001, respectively). Reward was inversely correlated with CIMT (adjusted r2=0.282, p<0.001), controlling for age, hypertension, diabetes mellitus, hyperlipidaemia and body mass index. For men, a similar pattern of associations was observed, but the associations were lost after adjustment for confounders.

Conclusions

Our results show that effort, overcommitment and ERI may be associated with early atherosclerosis predicted by CIMT in women, and reward is inversely related to CIMT.
Distribution and Use Efficiency of Photosynthetically Active Radiation in Strip Intercropping of Maize and Soybean
Authors: Gao Yang , Duan Aiwang , Qiu Xinqiang , Sun Jingsheng , Zhang Junpeng , Liu Hao , Wang Hezhou
Published: July 2010

An experiment was conducted at Shangqiu Agro‐Ecosystem Experimental Station in 2006–2008 to investigate the distribution and use efficiency of photosynthetically active radiation (PAR). The soil was classified as a Eutric Cambisol. Four treatments were compared: (i) sole crop maize (Zea maysL.) (SM); (ii) sole crop soybean [Glycine max(L.) Merr.] (SSB); (iii) three rows of soybean alternated with one row of maize (I1); and (iv) three rows of soybean alternated with two rows of maize (I2). Observed fraction of radiation intercepted (F), radiation use efficiency (RUE), and harvest index (HI) revealed that PAR transmittance at the bottom of the soybean canopy adjacent to the maize was higher than that farther from the maize. However, this difference decreased as the crops developed. The averaged extinction coefficient (K) and RUE were 0.51 and 2.82 g MJ−1for I1and 0.50 and 2.78 g MJ−1for I2, respectively, compared with 0.46 and 3.18 g MJ−1for sole crop maize and 0.59 and 1.55 g MJ−1for sole crop soybean. The HI of I1and I2were 0.45 and 0.44 for maize and 0.35 and 0.36 for soybean, respectively. The HI of sole crop maize and sole crop soybean were 0.42 and 0.40, respectively. The mean land equivalent ratio (LER) for I1and I2was 1.65 and 1.71, respectively. Therefore, it can be concluded that intercropping usually had greater RUE than sole cropping, which may account for the yield advantage of intercropping.