bluuebunny/crossref_metadata_2025 huggingface dataset:
The Employer's Duty to Make Reasonable Adjustments. When is a Reasonable Adjustment, Not Reasonable?
Authors: Bunbury Stephen
Published: October 2011

This article considers the impact of the reasonable adjustments duty imposed upon employers in section 4A of the Disability Discrimination Act (1995) where a provision, criterion, practice, or physical feature of the premises of the employer places the disabled person at a substantial disadvantage in comparison with persons who are not disabled. It considers that while the duty to make reasonable adjustments has contributed to the rising rates of employment among disabled people, an examination of the Employment Tribunal and EAT Statistics (GB) conversely reveals that there has been a steady increase in cases of disability discrimination in recent years. It is argued that the complexity of section 4A and the ensuing case law have contributed to the rising tide of cases in this field and is a trend which is likely to continue for the foreseeable future.
Dynamite or Damp Squib?—An Assessment of Equal Value Law
Authors: Gregory Jeanne
Published: October 2011

Recognising the potentially explosive impact of the law on equal pay for work of equal value, the article examines the ways in which the legislative framework itself, in combination with some far-reaching changes in the organisation of the labour market, has had a stultifying effect on this potential. It considers some key developments in UK case law and assesses the impact of some landmark decisions from the European Court of Justice. The article focuses on three specific areas. First, it examines new developments in job evaluation, where, despite a growing appreciation of the ways in which gender bias occurs, employers have retained the initiative, largely due to the ‘job evaluation bar’, which discourages close scrutiny by industrial tribunals. Second, the article looks at the legal defences available to employers, particularly the ‘market forces’ defence, and argues that such defences cut across the principle of equal pay, both substantively and procedurally. Third, the growth in merit payment systems and evidence of their potential gender bias is examined. The article concludes that equal pay law is in need of a fundamental overhaul if it is to meet the challenges of the contemporary labour market.
National Vocations Qualifications (NVQs) in Prisons: A Reflection of Effort and Achievement or the Perpetuation of Existing Patterns of Discrimination?
Authors: Bermingham Vera
Published: October 2011

The purpose of this article is to examine the extent to which gender or racial stereotypes are used to categorise or stigmatise inmates in the allocation of work, training and education in prisons. In setting out the impact of recent legislative reforms, the article begins by outlining the effects of the Further and Higher Education Act 1992 and the changes resulting from the introduction of National Vocational Qualifications (NVQs) to the prison regime. The requirement, for the purposes of Sentence Planning, of documentary evidence of an inmate's education and training profile will be seen to have far reaching effects at all stages through a prisoner's sentence; and beyond, for the many prisoners who will be subject to a period of compulsory supervision after release. Yet, it will also be shown that the system operates to allow highly discriminatory decisions to be taken without proper accountability. The effectiveness and implementation of the Prison Department's equal opportunities policy will be considered. The article will conclude by recommending further research that specifically focuses on the allocation of opportunities for education and training for prisoners.
Discrimination and Equality in the Workplace: Defining Affirmative Action and its Role and Limitations*
Authors: Human Linda
Published: October 2011

The objective of this contribution is to present an overview of what legislation relating to employment equity might look like and how such legislation could be implemented in practice. Areas covered include an attempt to clarify the confusion between concepts such as affirmative action; employment equity and managing diversity; a definition of affirmative action; the kinds of legislative requirements arising from such a definition and the practical implementation thereof.
Racial Grounds: a Definition of Identity?
Authors: MacEwen Martin
Published: October 2011

This paper examines the meaning of ‘Racial Grounds’ in terms of legal definition and also the social implications which may stem from this. The UK legislation against racial discrimination shares some terminology with international and regional conventions and treaties but a broader definition is frequently extended to the latter. The UK definition of racial discrimination includes ‘race, colour, nationality and ethnic or national origin’. These terms are examined and some practical difficulties identified. Recent cases have suggested that to discriminate against someone on the grounds of his or her being English, Welsh or Scottish may not offend the Race Relations Act 1976. Such exclusion is against the spirit of the protection of human rights by international law and, the author suggests, is contrary to the commonsense interpretation of the legislation which has previously been followed.
The Coming of Communitarian Rights: Are ‘Third-Generation’ Human Rights Really ‘First-Generation Rights?
Authors: Juss Satvinder
Published: October 2011

This article considers the limits of Western rights discourse in relation to the developing world, with a particular focus on Africa, and argues that the rights debate is ideologically driven, with its emphases on ‘first-generation’ civil and political rights. For the former European colonial territories, which comprise much of the developing world, it is the so-called ‘third-generation’ rights of communal solidarity and national development that are of paramount importance. This article argues that human rights are socially constructed, bearing little relation to the physical world, and that the history of international human rights evolution — predicated on parity, equity and justice on a. universal scale — has now come full circle to demand recognition of ‘third-generation’ rights as equally important rights on par with ‘first-generation’ rights in the West.
Age Discrimination in the United Kingdom
Authors: Meenan Helen
Published: October 2011

There is currently no legislation in the UK dealing with age discrimination in any area. This article focuses on the question of ageism in employment and outlines the UK Government's present voluntary and educative policy towards this problem. It points out deficiencies in this approach, not least lack of enforcement or a remedy for victims. The ‘demographic revolution’ resulting from an already ageing UK population, makes the need for effective protection against ageism in employment, more urgent than ever before. The question whether legislation for age discrimination would work in the UK is also addressed. In the absence of specific statutory protection for age, it may be possible to obtain redress by claiming indirect gender, race or disability discrimination under existing British law on these areas. This is however inadequate to tackle the very real problem of ageism in the workplace. A number of studies have recommended appropriate equal opportunities policies and an holistic human resources strategy to deal with this issue. These have some merit but on their own will not achieve a uniform and acceptable outcome.
Living alone with dementia
Authors: Duane Fleur , Brasher Kathleen , Koch Susan
Published: October 2011

This paper details the findings of an exploratory study undertaken in 2009 into the older population who live alone with dementia, as part of a wider study into the phenomenon of living alone in older age with a cognitive impairment or early stage dementia. Interviews were undertaken with 19 older people who live alone with cognitive impairment or early stage dementia, and field notes were taken during interview visits. Throughout this paper, older people who live alone with a cognitive impairment or dementia who participated in the study will be referred to by pseudonym. Overall, the findings give insight into the lives of these people and how they remain connected to and supported by others. These findings will contribute to the knowledge of this group, which may be considered in future research and service delivery.
The ambiguous relationships between aging and Alzheimer's disease: A critical literature review
Authors: Scodellaro Claire , Pin Stéphanie
Published: October 2011

One reason for the rise in the prevalence of Alzheimer's disease (AD) since the 1980s is the new association between the disease and aging. This paper explores the current representations of AD, questioning their relationships to aging, thanks to a literature review of 49 articles published in French and in English between 1995 and June 2010. Aging appears to be a concurrent diagnosis for AD, both for the lay public and for health professionals, but this confusion, which can be interpreted as a lack of medicalization of memory loss on the conceptual level, does not necessarily constitute an obstacle to medical intervention. The transformation of senile dementia into AD can diminish, as well as reinforce, stigmatization of people with AD. Moreover, elderly people with AD are subjected to both the persisting stigmas of aging and of dementia as well as, for most of them, that of feminine cognitive incompetence.
Perspective Taking Through Narratives
Authors: Dodd Janet L. , Ocampo Alaine , Kennedy Kelly S.
Published: October 2011

This study investigated the use of a narrative-based language intervention program for teaching perspective-taking skills to students with autism spectrum disorders (ASD). The participants consisted of 18 students between the ages of 9 years 7 months and 12 years 2 months ( M = 10:8) who had a diagnosis of an ASD. Students received 500 minutes of either a narrative-based intervention that focused on teaching perspective taking (PTI) or a traditional narrative-based language intervention (NBLI) that focused on story elements and semantics. Intervention was provided in small groups consisting of five students and one speech-language pathologist. The participants who received the PTI demonstrated greater growth in their ability to retell the story from the perspective of different characters compared to those who participated in the NBLI. Clinical implications are included.
Does clozapine cause or worsen obsessive compulsive symptoms? An analysis and literature review
Authors: Bleakley Stephen , Brown David , Taylor David
Published: October 2011

Background: Clozapine is the most effective antipsychotic in treatment-resistant schizophrenia but its use portends with a high burden of adverse reactions. One adverse event reported both in case reports and cross-sectional surveys is the emergence or worsening of obsessive compulsive symptoms (OCS).

Objectives: This study presents a retrospective review of a UK cohort of clozapine-treated individuals with the aim to further investigate the complex relationship between clozapine and OCS.

Methods: An extensive review of the medical records of 49 patients receiving clozapine in the Southampton area was undertaken. We searched for a diagnosis of obsessive compulsive disorder, signs or symptoms of obsessive compulsive disorder or the prescribing of selected antidepressants the year before clozapine initiation and the year after.

Results: Fifteen patients (31%) had reports of OCS during the 2-year data collection period. Twelve patients (24%) had OCS before clozapine initiation while only 7 (14%) had symptoms after clozapine was initiated. De novo OCS were reported in three (6%) cases after 5–9 months of clozapine treatment.

Conclusions: As with previous studies it was not possible to establish a definitive link between clozapine and OCS. Clinicians should be mindful of the common comorbidity of OCS and schizophrenia and the possible increased risk incurred when starting clozapine.
Metabolic, endocrinologic and cardiac effects of amisulpride: a 24-week follow-up study
Authors: Kotan Zeynep , Ertepe Berrin , Akkaya Cengiz , Sarandol Emre , Ozkaya Güven , Kirli Selçuk
Published: October 2011

Background: Amisulpride is a second-generation antipsychotic which has been proved to be effective in the control of both positive and negative symptoms of schizophrenia. In this study we aimed to determine metabolic, endocrinologic and cardiac effects of amisulpride commonly used in our clinical practice.

Methods: A total of 18 patients (11 males, 7 females) diagnosed with schizophrenia received amisulpride at the dosage of 800 mg/day and were followed up for 24 weeks. Positive and negative psychotic symptoms, extrapyramidal and sexual side effects, metabolic, endocrinologic and cardiac parameters were evaluated at regular intervals.

Results: Significant improvement in both positive and negative symptoms was observed in patients starting from the second week of treatment. Prolactin levels increased significantly both in men and women starting from the measurement on day 4. Prolactin elevation was significantly higher in women than in men. Increase in total cholesterol level became significant at week 24. No other significant difference was observed between weeks 1 and 24 regarding the other parameters.

Conclusions: The clinical data from the present study supports the fact that amisulpride is an effective and safe antipsychotic drug, but elevates prolactin levels in both sexes.
Trends in the prevalence of asthma and allergic rhinitis in Italy between 1991 and 2010
Authors: de Marco R. , Cappa V. , Accordini S. , Rava M. , Antonicelli L. , Bortolami O. , Braggion M. , Bugiani M. , Casali L. , Cazzoletti L. , Cerveri I. , Fois A.G. , Girardi P. , Locatelli F. , Marcon A. , Marinoni A. , Panico M.G. , Pirina P. , Villani S. , Zanolin M.E. , Verlato G.
Published: October 2011

The prevalence of asthma increased worldwide until the 1990s, but since then there has been no clear temporal pattern.

The present study aimed to assess time trends in the prevalence of current asthma, asthma-like symptoms and allergic rhinitis in Italian adults from 1990 to 2010.

The same screening questionnaire was administered by mail or phone to random samples of the general population (age 20–44 yrs) in Italy, in the frame of three multicentre studies: the European Community Respiratory Health Survey (ECRHS) (1991–1993; n=6,031); the Italian Study on Asthma in Young Adults (ISAYA) (1998–2000; n=18,873); and the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (2007–2010; n=10,494). Time trends in prevalence were estimated using Poisson regression models in the centres that repeated the survey at different points in time.

From 1991 to 2010, the median prevalence of current asthma, wheezing and allergic rhinitis increased from 4.1% to 6.6%, from 10.1% to 13.9% and from 16.8% to 25.8%, respectively. The prevalence of current asthma was stable during the 1990s and increased (relative risk 1.38, 95% CI 1.19–1.59) from 1998–2000 to 2007–2010, mainly in subjects who did not report allergic rhinitis. The prevalence of allergic rhinitis has increased continuously since 1991.

The asthma epidemic is not over in Italy. During the past 20 yrs, asthma prevalence has increased by 38%, in parallel with a similar increase in asthma-like symptoms and allergic rhinitis.
Quantitative assessment of chronic lung disease of infancy using computed tomography
Authors: Sarria E.E. , Mattiello R. , Rao L. , Tiller C.J. , Poindexter B. , Applegate K.E. , Granroth-Cook J. , Denski C. , Nguyen J. , Yu Z. , Hoffman E. , Tepper R.S.
Published: October 2011

The aims of this study were to determine whether infants and toddlers with chronic lung disease of infancy (CLDI) have smaller airways and lower lung density compared with full-term healthy controls.

Multi-slice computed tomography (CT) chest scans were obtained at elevated lung volumes during a brief respiratory pause in sedated infants and toddlers; 38 CLDI were compared with 39 full-term controls. For CLDI subjects, gestational age at birth ranged from 25 to 29 weeks. Airway size was measured for the trachea and the next three to four generations into the right lower lobe; lung volumes and tissue density were also measured.

The relationship between airway size and airway generation differed between the CLDI and full-term groups; the sizes of the first and second airway generations were larger in the shorter CLDI than in the shorter full-term subjects. The increased size in the airways in the CLDI subjects was associated with increasing mechanical ventilation time in the neonatal period. CLDI subjects had a greater heterogeneity of lung density compared with full-term subjects.

Our results indicate that quantitative analysis of multi-slice CT scans at elevated volumes provides important insights into the pulmonary pathology of infants and toddlers with CLDI.
Long-term follow-up after bronchoscopic lung volume reduction in patients with emphysema
Authors: Venuta Federico , Anile Marco , Diso Daniele , Carillo Carolina , De Giacomo Tiziano , D'Andrilli Antonio , Fraioli Francesco , Rendina Erino A. , Coloni Giorgio F.
Published: October 2011

Bronchoscopic lung volume reduction (BLVR) is a novel emphysema therapy. We evaluated long-term outcome in patients with heterogeneous emphysema undergoing BLVR with one-way valves.

40 patients undergoing unilateral BLVR entered our study. Pre-operative mean forced expiratory volume in 1 s (FEV1) was 0.88 L·s−1(23%), total lung capacity was 7.45 L (121%), intrathoracic gas volume was 6 L (174%), residual volume (RV) was 5.2 L (232%), and the 6-min walk test (6MWT) was 286 m. All patients required supplemental oxygen; the Medical Research Council (MRC) dyspnoea score was 3.9. High-resolution computed tomography (HRCT) results were reviewed to assess the presence of interlobar fissures.

33 patients had a follow-up of >12 months (median 32 months). 37.5% of the patients had visible interlobar fissures. 40% of the patients died during follow-up. Three patients were transplanted and one underwent lung volume reduction surgery. Supplemental oxygen, FEV1, RV, 6MWT and MRC score showed a statistically significant improvement (p≤0.0001, p=0.004, p=0.03, p=0.003 and p<0.0001, respectively). Patients with visible fissures had a functional advantage.

BLVR is feasible and safe. Long-term sustained improvements can be achieved. HRCT-visible interlobar fissures are a favourable prognostic factor.
Resolution of acute lung injury and inflammation: a translational mouse model
Authors: Patel Brijesh V. , Wilson Michael R. , Takata Masao
Published: October 2011

Previous animal models of acute lung injury (ALI) are limited as they only reproduce part of the complex pathobiology of clinical ALI. Here we develop a translational mouse model of ALI, which not only reflects the major clinical and pathological features but also enables investigation into ALI resolution.

Anaesthetised mice underwent orotracheal instillation of hydrochloric acid. During the immediate period after instillation, mice were carefully maintained with supplemental oxygen to avoid mortality. At specified time-points, lung injury was assessed by analysis of blood gases, respiratory mechanics, bronchoalveolar lavage fluid, alveolar fluid clearance and lung histology.

Animals exhibited significant weight loss, decreased oxygenation, increased respiratory elastance and pulmonary inflammation (intra-alveolar leukocyte influx/cytokine levels and histological injury scores). Moreover, mice displayed alveolar–capillary barrier dysfunction/epithelial injury as reflected by increased alveolar protein, lung wet/dry weight ratio and soluble receptor for advanced glycation end-products, as well as reduced alveolar fluid clearance. These injury parameters peaked between days 1 and 3, followed by almost complete recovery over days 5–10. Histology showed evidence of fibrosis on day 10.

The results indicate that this resolving model of acid aspiration represents a powerful experimental tool to investigate the injurious, inflammatory, fibrotic, and resolving and reparative processes of ALI.
Unmasking tuberculosis in the era of antiretroviral treatment
Authors: Lapadula Giuseppe , Soria Alessandro , Bandera Alessandra , Squillace Nicola , Sabbatini Francesca , Franzetti Fabio , Migliori Giovanni Battista , Gori Andrea
Published: October 2011

Tuberculosis (TB) can develop soon after antiretroviral treatment initiation, as the result of restoration of the anti-TB specific immune response. This form of the disease is often defined as “unmasked TB”, and it represents a major challenge for severely immune-suppressed HIV-infected subjects initiating treatment. Emergence of previously unrecognised TB disease occurs frequently in countries where TB/HIV co-infection is common, and where antiretroviral treatment has become increasingly accessible. The challenges posed by unmasked TB, such as its high incidence, the lack of reliable diagnostic tools and the uncertainties on its optimal management, may hamper our ability to face the TB/HIV epidemic. Therefore, unmasked TB appears a major threat to global health and poses additional barriers to successful HIV/AIDS care and treatment programmes.

This review focuses on the epidemiology, immunopathogenesis and clinical manifestations of unmasked TB, and provides evidence-based recommendations for management and care of the disease.
Evasion of COPD in smokers: at what price?
Authors: Cosio Manuel G. , Saetta Marina
Published: October 2011

Investigations toward the understanding of chronic obstructive pulmonary disease (COPD) have been directed, so far, to the study of mechanisms leading to the disease. We believe that understanding why ∼80% of smokers evade COPD and how this evasion is accomplished might be a fruitful endeavour that could advance knowledge of the development of the disease. Since the inflammatory infiltrate smokers develop seems to be the key element leading to the lung destruction in COPD, the understanding of the possible ways inflammation can be dampened, as well as its consequences, ought to be important. We review here some of the mechanisms by which inflammation is controlled: by the post-translational regulons, by the mechanisms preventing full activation of dendritic cells and by the regulatory T-cells. The potential role of the M2 alveolar macrophage phenotype and the newly described myeloid-derived suppressor cells is mentioned. We also point out that evasion comes at a price, as healthy smokers might be immunosuppressed to some extent and unable to prevent the development of cancer, certainly less so than in severe COPD, where immunity is heightened. Probably, the knowledge of the mechanisms of evasion from COPD could add significantly to the understanding of those leading to the disease.
Scenario driven data modelling: a method for integrating diverse sources of data and data streams
Authors: Griffith Shelton D , Quest Daniel J , Brettin Thomas S , Cottingham Robert W
Published: October 2011

Background

Biology is rapidly becoming a data intensive, data-driven science. It is essential that data is represented and connected in ways that best represent its full conceptual content and allows both automated integration and data driven decision-making. Recent advancements in distributed multi-relational directed graphs, implemented in the form of the Semantic Web make it possible to deal with complicated heterogeneous data in new and interesting ways.

Results

This paper presents a new approach, scenario driven data modelling (SDDM), that integrates multi-relational directed graphs with data streams. SDDM can be applied to virtually any data integration challenge with widely divergent types of data and data streams. In this work, we explored integrating genetics data with reports from traditional media. SDDM was applied to the New Delhi metallo-beta-lactamase gene (NDM-1), an emerging global health threat. The SDDM process constructed a scenario, created a RDF multi-relational directed graph that linked diverse types of data to the Semantic Web, implemented RDF conversion tools (RDFizers) to bring content into the Sematic Web, identified data streams and analytical routines to analyse those streams, and identified user requirements and graph traversals to meet end-user requirements.

Conclusions

We provided an example where SDDM was applied to a complex data integration challenge. The process created a model of the emerging NDM-1 health threat, identified and filled gaps in that model, and constructed reliable software that monitored data streams based on the scenario derived multi-relational directed graph. The SDDM process significantly reduced the software requirements phase by letting the scenario and resulting multi-relational directed graph define what is possible and then set the scope of the user requirements. Approaches like SDDM will be critical to the future of data intensive, data-driven science because they automate the process of converting massive data streams into usable knowledge.
Evaluation of the coverage and depth of transcriptome by RNA-Seq in chickens
Authors: Wang Ying , Ghaffari Noushin , Johnson Charles D , Braga-Neto Ulisses M , Wang Hui , Chen Rui , Zhou Huaijun
Published: October 2011

Background

RNA-Seq is the recently developed high-throughput sequencing technology for profiling the entire transcriptome in any organism. It has several major advantages over current hybridization-based approach such as microarrays. However, the cost per sample by RNA-Seq is still prohibitive for most laboratories. With continued improvement in sequence output, it would be cost-effective if multiple samples are multiplexed and sequenced in a single lane with sufficient transcriptome coverage. The objective of this analysis is to evaluate what sequencing depth might be sufficient to interrogate gene expression profiling in the chicken by RNA-Seq.

Results

Two cDNA libraries from chicken lungs were sequenced initially, and 4.9 million (M) and 1.6 M (60 bp) reads were generated, respectively. With significant improvements in sequencing technology, two technical replicate cDNA libraries were re-sequenced. Totals of 29.6 M and 28.7 M (75 bp) reads were obtained with the two samples. More than 90% of annotated genes were detected in the data sets with 28.7-29.6 M reads, while only 68% of genes were detected in the data set with 1.6 M reads. The correlation coefficients of gene expression between technical replicates within the same sample were 0.9458 and 0.8442. To evaluate the appropriate depth needed for mRNA profiling, a random sampling method was used to generate different number of reads from each sample. There was a significant increase in correlation coefficients from a sequencing depth of 1.6 M to 10 M for all genes except highly abundant genes. No significant improvement was observed from the depth of 10 M to 20 M (75 bp) reads.

Conclusion

The analysis from the current study demonstrated that 30 M (75 bp) reads is sufficient to detect all annotated genes in chicken lungs. Ten million (75 bp) reads could detect about 80% of annotated chicken genes, and RNA-Seq at this depth can serve as a replacement of microarray technology. Furthermore, the depth of sequencing had a significant impact on measuring gene expression of low abundant genes. Finally, the combination of experimental and simulation approaches is a powerful approach to address the relationship between the depth of sequencing and transcriptome coverage.
Overall and worst gleason scores are equally good predictors of prostate cancer progression
Authors: Tolonen Teemu T , Kujala Paula M , Tammela Teuvo LJ , Tuominen Vilppu J , Isola Jorma J , Visakorpi Tapio
Published: October 2011

Background

Gleason scoring has experienced several modifications during the past decade. So far, only one study has compared the prognostic abilities of worst (WGS) and overall (OGS) modified Gleason scores after the ISUP 2005 conference. Prostatic needle biopsies are individually paraffin-embedded in 57% of European pathology laboratories, whereas the rest of laboratories embed multiple (2 - 6) biopsies per one paraffin-block. Differences in the processing method can have a far-reaching effect, because reporting of the Gleason score (GS) is different for individually embedded and pooled biopsies, and GS is one of the most important factors when selecting treatment for patients.

Methods

The study material consisted of needle biopsies from 236 prostate cancer patients that were endocrine-treated in 1999-2003. Biopsies from left side and right side were embedded separately. Haematoxylin-eosin-stained slides were scanned and analyzed on web-based virtual microscopy. Worst and overall Gleason scores were assessed according to the modified Gleason score schema after analyzing each biopsy separately. The compound Gleason scores (CGS) were obtained from the original pathology reports. Two different grade groupings were used: GS 6 or less vs. 7 vs. 8 or above; and GS 7(3 + 4) or less vs. 7(4 + 3) and 8 vs. 9-10. The prognostic ability of the three scoring methods to predict biochemical progression was compared with Kaplan-Meier survival analysis and univariate and multivariate Cox regression analyses.

Results

The median follow-up time of the patients was 64.5 months (range 0-118). The modified GS criteria led to upgrading of the Gleason sums compared to the original CGS from the pathology reports 1999-2003 (mean 7.0 for CGS, 7.5 for OGS, 7.6 for WGS). In 43 cases WGS was > OGS. In a univariate analysis the relative risks were 2.1 (95%-confidence interval 1.8-2.4) for CGS, 2.5 (2.1-2.8) for OGS, and 2.6 (2.2-2.9) for WGS. In a multivariate analysis, OGS was the only independent prognostic factor.

Conclusions

All of the three Gleason scoring methods are strong predictors of biochemical recurrence. The use of modified Gleason scoring leads to upgrading of GS, but also improves the prognostic value of the scoring. No significant prognostic differences between OGS and WGS could be shown, which may relate to the apparent narrowing of the GS scale from 2-10 to 5-10 due to the recent modifications.
Prevalence of at-risk genotypes for genotoxic effects decreases with age in a randomly selected population in Flanders: a cross sectional study
Authors: Ketelslegers Hans B , Godschalk Roger WL , Gottschalk Ralph WH , Knaapen Ad M , Koppen Gudrun , Schoeters Greet , Baeyens Willy F , Nelen Vera , Geraedts Joep PM , van Delft Joost HM , Kleinjans Jos CS , van Larebeke Nicolas A
Published: October 2011

Background

We hypothesized that in Flanders (Belgium), the prevalence of at-risk genotypes for genotoxic effects decreases with age due to morbidity and mortality resulting from chronic diseases. Rather than polymorphisms in single genes, the interaction of multiple genetic polymorphisms in low penetrance genes involved in genotoxic effects might be of relevance.

Methods

Genotyping was performed on 399 randomly selected adults (aged 50-65) and on 442 randomly selected adolescents. Based on their involvement in processes relevant to genotoxicity, 28 low penetrance polymorphisms affecting the phenotype in 19 genes were selected (xenobiotic metabolism, oxidative stress defense and DNA repair, respectively 13, 6 and 9 polymorphisms). Polymorphisms which, based on available literature, could not clearly be categorized a priori as leading to an 'increased risk' or a 'protective effect' were excluded.

Results

The mean number of risk alleles for all investigated polymorphisms was found to be lower in the 'elderly' (17.0 ± 2.9) than the 'adolescent' (17.6 ± 3.1) subpopulation (P = 0.002). These results were not affected by gender nor smoking. The prevalence of a high (> 17 = median) number of risk alleles was less frequent in the 'elderly' (40.6%) than the 'adolescent' (51.4%) subpopulation (P = 0.002). In particular for phase II enzymes, the mean number of risk alleles was lower in the 'elderly' (4.3 ± 1.6 ) than the 'adolescent' age group (4.8 ± 1.9) P < 0.001 and the prevalence of a high (> 4 = median) number of risk alleles was less frequent in the 'elderly' (41.3%) than the adolescent subpopulation (56.3%, P < 0.001). The prevalence of a high (> 8 = median) number of risk alleles for DNA repair enzyme-coding genes was lower in the 'elderly' (37,3%) than the 'adolescent' subpopulation (45.6%, P = 0.017).

Conclusions

These observations are consistent with the hypothesis that, in Flanders, the prevalence of at-risk alleles in genes involved in genotoxic effects decreases with age, suggesting that persons carrying a higher number of at risk alleles (especially in phase II xenobiotic-metabolizing or DNA repair genes) are at a higher risk of morbidity and mortality from chronic diseases. Our findings also suggest that, regarding risk of disease associated with low penetrance polymorphisms, multiple polymorphisms should be taken into account, rather than single ones.
A binary matrix factorization algorithm for protein complex prediction
Authors: Tu Shikui , Chen Runsheng , Xu Lei
Published: October 2011

Background

Identifying biologically relevant protein complexes from a large protein-protein interaction (PPI) network, is essential to understand the organization of biological systems. However, high-throughput experimental techniques that can produce a large amount of PPIs are known to yield non-negligible rates of false-positives and false-negatives, making the protein complexes difficult to be identified.

Results

We propose a binary matrix factorization (BMF) algorithm under the Bayesian Ying-Yang (BYY) harmony learning, to detect protein complexes by clustering the proteins which share similar interactions through factorizing the binary adjacent matrix of a PPI network. The proposed BYY-BMF algorithm automatically determines the cluster number while this number is pre-given for most existing BMF algorithms. Also, BYY-BMF’s clustering results does not depend on any parameters or thresholds, unlike the Markov Cluster Algorithm (MCL) that relies on a so-called inflation parameter. On synthetic PPI networks, the predictions evaluated by the known annotated complexes indicate that BYY-BMF is more robust than MCL for most cases. On real PPI networks from the MIPS and DIP databases, BYY-BMF obtains a better balanced prediction accuracies than MCL and a spectral analysis method, while MCL has its own advantages, e.g., with good separation values.
ATPsite: sequence-based prediction of ATP-binding residues
Authors: Chen Ke , Mizianty Marcin J , Kurgan Lukasz
Published: October 2011

Background

ATP is a ubiquitous nucleotide that provides energy for cellular activities, catalyzes chemical reactions, and is involved in cellular signalling. The knowledge of the ATP-protein interactions helps with annotation of protein functions and finds applications in drug design. The sequence to structure annotation gap motivates development of high-throughput sequence-based predictors of the ATP-binding residues. Moreover, our empirical tests show that the only existing predictor, ATPint, is characterized by relatively low predictive quality.

Methods

We propose a novel, high-throughput machine learning-based predictor, ATPsite, which identifies ATP-binding residues from protein sequences. Our predictor utilizes Support Vector Machine classifier and a comprehensive set of input features that are based on the sequence, evolutionary profiles, and the sequence-predicted structural descriptors including secondary structure, solvent accessibility, and dihedral angles.

Results

The ATPsite achieves significantly higher Mathews Correlation Coefficient (MCC) and Area Under the ROC Curve (AUC) values when compared with the existing methods including the ATPint, conservation-based rate4site, and alignment-based BLAST predictors. We also assessed the effectiveness of individual input types. The PSSM profile, the conservation scores, and certain features based on amino acid groups are shown to be more effective in predicting the ATP-binding residues than the remaining feature groups.

Conclusions

Statistical tests show that ATPsite significantly outperforms existing solutions. The consensus of the ATPsite with the sequence-alignment based predictor is shown to give further improvements.
CFTR Mediates Noradrenaline-Induced ATP Efflux from DRG Neurons
Authors: Kanno Takeshi , Nishizaki Tomoyuki
Published: October 2011

In our earlier study, noradrenaline (NA) stimulated ATP release from dorsal root ganglion (DRG) neurons as mediated via β3 adrenoceptors linked to Gs protein involving protein kinase A (PKA) activation, to cause allodynia. The present study was conducted to understand how ATP is released from DRG neurons. In an outside-out patch-clamp configuration from acutely dissociated rat DRG neurons, single-channel currents, sensitive to the P2X receptor inhibitor PPADS, were evoked by approaching the patch-electrode tip close to a neuron, indicating that ATP is released from DRG neurons, to activate P2X receptor. NA increased the frequency of the single-channel events, but such NA effect was not found for DRG neurons transfected with the siRNA to silence the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In the immunocytochemical study using acutely dissociated rat DRG cells, CFTR was expressed in neurons alone, but not satellite cells, fibroblasts, or Schwann cells. It is concluded from these results that CFTR mediates NA-induced ATP efflux from DRG neurons as an ATP channel.
Hyperbaric oxygen therapy as an adjunctive treatment for sternal infection and osteomyelitis after sternotomy and cardiothoracic surgery
Authors: Yu Wen-Kuang , Chen Yen-Wen , Shie Huei-Guan , Lien Te-Cheng , Kao Hsin-Kuo , Wang Jia-Horng
Published: October 2011

Purpose

A retrospective study to evaluate the effect of hyperbaric oxygen (HBO2) therapy on sternal infection and osteomyelitis following median sternotomy.

Materials and methods

A retrospective analysis of patients who received sternotomy and cardiothoracic surgery which developed sternal infection and osteomyelitis between 2002 and 2009. Twelve patients who received debridement and antibiotic treatment were selected, and six of them received additional HBO2 therapy. Demographic, clinical characteristics and outcome were compared between patients with and without HBO2 therapy.

Results

HBO2 therapy did not cause any treatment-related complication in patients receiving this additional treatment. Comparisons of the data between two study groups revealed that the length of stay in ICU (8.7 ± 2.7 days vs. 48.8 ± 10.5 days, p < 0.05), duration of invasive (4 ± 1.5 days vs. 34.8 ± 8.3 days, p < 0.05) and non-invasive (4 ± 1.9 days vs. 22.3 ± 6.2 days, p < 0.05) positive pressure ventilation were all significantly lower in patients with additional HBO2 therapy, as compared to patients without HBO2 therapy. Hospital mortality was also significantly lower in patients who received HBO2 therapy (0 case vs. 3 cases, p < 0.05), as compared to patients without the HBO2 therapy.

Conclusions

In addition to primary treatment with debridement and antibiotic use, HBO2 therapy may be used as an adjunctive and safe treatment to improve clinical outcomes in patients with sternal infection and osteomyelitis after sternotomy and cardiothoracic surgery.
Detectability of petrophysical properties of subsurface CO2-saturated aquifer reservoirs using surface geophysical methods
Authors: JafarGandomi Arash , Curtis Andrew
Published: October 2011

The process of capturing carbon dioxide ([Formula: see text]) and injecting it into deep saline aquifers is becoming an important method to reduce future atmospheric emissions of [Formula: see text]. Key challenges facing carbon capture and storage (CCS) are the storage reservoir's size and safety. The storage size can be addressed by focusing on large saline aquifer reservoirs. The safety concern may be lower if [Formula: see text] is injected into depleted hydrocarbon reservoirs because their cap-rock integrity is already proven, but such capping systems are generally potentially compromised by poorly cemented abandoned wells, and compared to saline aquifers, their storage size is small. Therefore, the long-term focus of CCS is on saline aquifers. To reduce the corresponding risks, comprehensive long-term monitoring is inevitable.
Analyses of vibrator performance using long and short sweeps
Authors: Wei Zhouhong , Phillips Thomas F. , Pecholcs Peter I.
Published: October 2011

There appears to be a growing interest in improving subsurface seismic imaging by increasing spatial sampling as a result of increased receiver and/or source density. Cost-effectively improving spatial sampling, however, requires increased vibrator productivity. Some high-productivity techniques now used in survey operations are slip-sweep and independent simultaneous shooting (ISS). However, there is a debate that such methods should be used only by vibrator groups with short sweeps or single vibrators with long sweeps. Can we remove all in-field signal-to-noise enhancement processes and rely strictly on the seismic processing of high trace-density volumes? This paper focuses on the vibrator itself and determines the vibrator performance when driven by short and long sweeps. The experimental results demonstrate that a minimum sweep length is required to avoid significant degradation in vibrator performance at low frequencies (below 20 Hz). Above 20 Hz, the force power spectra with various sweep lengths remain consistent. Moreover, when coupling is poor, a short sweep will produce a better spectrum of the vibrator ground force than a long sweep.
Pilot Induction Regimen Incorporating Pharmacokinetically Guided Topotecan for Treatment of Newly Diagnosed High-Risk Neuroblastoma: A Children's Oncology Group Study
Authors: Park Julie R. , Scott Jeffrey R. , Stewart Clinton F. , London Wendy B. , Naranjo Arlene , Santana Victor M. , Shaw Peter J. , Cohn Susan L. , Matthay Katherine K.
Published: October 2011

Purpose

To assess the feasibility of adding dose-intensive topotecan and cyclophosphamide to induction therapy for newly diagnosed high-risk neuroblastoma (HRNB).

Patients and Methods

Enrolled patients received two cycles of topotecan (approximately 1.2 mg/m2/d) and cyclophosphamide (400 mg/m2/d) for 5 days followed by four cycles of multiagent chemotherapy (Memorial Sloan-Kettering Cancer Center [MSKCC] regimen). Pharmacokinetically guided topotecan dosing (target systemic exposure with area under the curve of 50 to 70 ng/mL/hr) was performed. Peripheral-blood stem cell (PBSC) harvest and surgical resection of residual primary tumor occurred after cycles 2 and 5, respectively. Patients achieving at least a partial response received myeloablative chemotherapy with PBSC rescue and radiation to the presurgical primary tumor volume. Oral 13-cis-retinoic acid maintenance therapy was administered twice daily for 14 days in six 28-day cycles.

Results

Thirty-one patients were enrolled onto the study. No deaths related to toxicity or dose-limiting toxicities occurred during induction. Mucositis rarely occurred after topotecan cycles (9.7%) in contrast to 30% after MSKCC cycles. Thirty patients underwent PBSC collection with median 31.1 × 106 CD34+ cells/kg (range, 1.8 to 541.8 × 106 CD34+ cells/kg), all negative for tumor contamination by immunocytochemical analysis. Targeted topotecan systemic exposure was achieved in 26 (84%) of 31 patients. At the end of induction, 26 patients (84%) had tumor response and one patient had progressive disease. In the overall cohort, 3-year event-free and overall survival were 37.8% ± 9.4% and 57.1% ± 9.4%, respectively.

Conclusion

This pilot induction regimen was well tolerated with expected and reversible toxicities. These data support investigation of efficacy in a phase III clinical trial for newly diagnosed HRNB.
Risk of Recurrence and Chemotherapy Benefit for Patients With Node-Negative, Estrogen Receptor–Positive Breast Cancer: Recurrence Score Alone and Integrated With Pathologic and Clinical Factors
Authors: Tang Gong , Cuzick Jack , Costantino Joseph P. , Dowsett Mitch , Forbes John F. , Crager Michael , Mamounas Eleftherios P. , Shak Steven , Wolmark Norman
Published: October 2011

Purpose

The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) –positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value.

Patients and Methods

From the National Surgical Adjuvant Breast and Bowel (NSABP) B-14 and translational research cohort of the Arimidex, Tamoxifen Alone or in Combination (TransATAC) studies, we included patients who received hormonal monotherapy, had ER-positive tumors, and RS and traditional clinicopathologic factors assessed (647 and 1,088, respectively). Individual patient risk assessments from separate Cox models were combined using meta-analysis to form an RS-pathology-clinical (RSPC) assessment of distant recurrence risk. Risk assessments by RS and RSPC were compared in node-negative (N0) patients. RSPC was compared with RS for predicting chemotherapy benefit in NSABP B-20.

Results

RSPC had significantly more prognostic value for distant recurrence than did RS (P < .001) and showed better separation of risk in the study population. RSPC classified fewer patients as intermediate risk (17.8% v 26.7%, P < .001) and more patients as lower risk (63.8% v 54.2%, P < .001) than did RS among 1,444 N0 ER-positive patients. In B-20, the interaction of RSPC with chemotherapy was not statistically significant (P = .10), in contrast to the previously reported significant interaction of RS with chemotherapy (P = .037).

Conclusion

RSPC refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk. Adding clinicopathologic measures did not seem to enhance the value of RS alone nor the individual biology RS identifies in predicting chemotherapy benefit.
Ruin excursions, the G/G/∞ queue, and tax payments in renewal risk models
Authors: Albrecher Hansjörg , Borst Sem C. , Boxma Onno J. , Resing Jacques
Published: October 2011

In this paper we investigate the number and maximum severity of the ruin excursion of the insurance portfolio reserve process in the Cramér–Lundberg model with and without tax payments. We also provide a relation of the Cramér–Lundberg risk model with the G/G/∞ queue and use it to derive some explicit ruin probability formulae. Finally, the renewal risk model with tax is considered, and an asymptotic identity is derived that in some sense extends the tax identity of the Cramér– Lundberg risk model.
Exit times for a class of random walks exact distribution results
Authors: Jacobsen Martin
Published: October 2011

For a random walk with both downward and upward jumps (increments), the joint distribution of the exit time across a given level and the undershoot or overshoot at crossing is determined through its generating function, when assuming that the distribution of the jump in the direction making the exit possible has a Laplace transform which is a rational function. The expected exit time is also determined and the paper concludes with exact distribution results concerning exits from bounded intervals. The proofs use simple martingale techniques together with some classical expansions of polynomials and Rouché's theorem from complex function theory.
A large deviation principle for Minkowski sums of heavy-tailed random compact convex sets with finite expectation
Authors: Mikosch Thomas , Pawlas Zbyněk , Samorodnitsky Gennady
Published: October 2011

We prove large deviation results for Minkowski sums Sn of independent and identically distributed random compact sets where we assume that the summands have a regularly varying distribution and finite expectation. The main focus is on random convex compact sets. The results confirm the heavy-tailed large deviation heuristics: ‘large’ values of the sum are essentially due to the ‘largest’ summand. These results extend those in Mikosch, Pawlas and Samorodnitsky (2011) for generally nonconvex sets, where we assumed that the normalization of Sn grows faster than n.