bluuebunny/crossref_metadata_2025 huggingface dataset:
Matched samples logistic regression in case-control studies with missing values: when to break the matches
Authors: Hansson Lisbeth , Khamis Harry J
Published: March 2008

Simulated data sets are used to evaluate conditional and unconditional maximum likelihood estimation in an individual case-control design with continuous covariates when there are different rates of excluded cases and different levels of other design parameters. The effectiveness of the estimation procedures is measured by method bias, variance of the estimators, root mean square error (RMSE) for logistic regression and the percentage of explained variation. Conditional estimation leads to higher RMSE than unconditional estimation in the presence of missing observations, especially for 1:1 matching. The RMSE is higher for the smaller stratum size, especially for the 1:1 matching. The percentage of explained variation appears to be insensitive to missing data, but is generally higher for the conditional estimation than for the unconditional estimation. It is particularly good for the 1:2 matching design. For minimizing RMSE, a high matching ratio is recommended; in this case, conditional and unconditional logistic regression models yield comparable levels of effectiveness. For maximizing the percentage of explained variation, the 1:2 matching design with the conditional logistic regression model is recommended.
A comparative study of the bias corrected estimates in logistic regression
Authors: Maiti Tapabrata , Pradhan Vivek
Published: March 2008

Logistic regression is frequently used in many areas of applied statistics. The maximum likelihood estimates (MLE) of the logistic regression parameters are usually computed using the iterative Newton—Raphson method. It is well known that these estimates are biased. Several methods are proposed to correct the bias of these estimates. Among them Firth (1993) and Cordeiro and McCullagh (1991) proposed two promising methods. The conditional exact method (CMLE) is popular for small-sample estimates, and is available in many software packages. In this article we compare these methods in terms of their bias. In general, our extensive simulations show that the methods proposed by Cordeiro and McCullagh and by Firth work well, though Cordeiro and McCullagh is slightly better in our simulations. In case of separation, Firth or CMLE can be used; however, a judicious approach is required when there is a wide variation in results. Two real data analyses are given exhibiting these properties. The data analysis also includes bootstrap results.
Mistakes in validating the accuracy of a prediction classifier in high-dimensional but small-sample microarray data
Authors: Lee Sunho
Published: March 2008

A major interest in gene expression microarray studies is to develop an accurate classifier which can be adopted in clinical practice. The usage of large numbers of genes with small data samples may lead to overfitting in classification, and generate promising, but often nonreproducible results. Therefore, assessing the reproducibility of a classifier is necessary. Appropriate methods for validating a developed classifier and estimating its predicting accuracy are discussed. In addition, some mistakes that can arise in the cross validation process are reviewed using published articles in prominent medical journals, to prevent the indefinite results of a classifier development from leading to inappropriate treatment.
Reframing nuclear power in the UK energy debate: nuclear power, climate change mitigation and radioactive waste
Authors: Bickerstaff K. , Lorenzoni I. , Pidgeon N.F. , Poortinga W. , Simmons P.
Published: March 2008

In the past decade, human influence on the climate through increased use of fossil fuels has become widely acknowledged as one of the most pressing issues for the global community. For the United Kingdom, we suggest that these concerns have increasingly become manifest in a new strand of political debate around energy policy, which reframes nuclear power as part of the solution to the need for low-carbon energy options. A mixed-methods analysis of citizen views of climate change and radioactive waste is presented, integrating focus group data and a nationally representative survey. The data allow us to explore how UK citizens might now and in the future interpret and make sense of this new framing of nuclear power—which ultimately centers on a risk—risk trade-off scenario. We use the term “reluctant acceptance” to describe how, in complex ways, many focus group participants discursively re-negotiated their position on nuclear energy when it was positioned alongside climate change. In the concluding section of the paper, we reflect on the societal implications of the emerging discourse of new nuclear build as a means of delivering climate change mitigation and set an agenda for future research regarding the (re)framing of the nuclear energy debate in the UK and beyond.
The Effects of Demographic Differences on Forming Intragroup Relationships
Authors: Valenti M. Alix , Rockett Tracey
Published: March 2008

Group behavior research suggests that differences among group members cause individuals to interact in ways that may enhance or weaken group performance. Dissimilarities among members may cause the development of negative attitudes about work groups, leading to dysfunctional performance. Network theorists have found that demographic factors influence individuals' tendency to form network ties within their organizations. This article bridges these findings, examining whether work group demographic differences affect a group member's tendency to form network ties with other group members or outside the work unit. In a study of 49 employees at a Midwest consulting firm, individual differences in sex and tenure predicted whether employees interacted within their work groups on advice and friendship dimensions, respectively, but did not affect the establishment of working relationships. Increased group heterogeneity tended to reduce the effect of demographic differences. Longer-service men were more likely to forge relationships within the work group than were short-term or female workers.
Effects of Nitric Oxide and Noradrenergic Activation in the Posterior Hypothalamus on Arterial Pressure Tolerance to Nitroglycerin in Rats
Authors: Guettler Diane L. , Ma Sheng-Xing
Published: March 2008

The effects of nitric oxide (NO) and noradrenergic activation in the posterior hypothalamus on arterial pressure tolerance induced by subcutaneous injection of nitroglycerin (NTG) was investigated in anesthetized Sprague-Dawley rats. Intravenous injections of NTG (3, 10, and 30 µg/kg) and sodium nitroprusside (1, 3, and 10 µg/kg) produced dose-dependant decreases in arterial blood pressure. Tolerance to NTG was produced by subcutaneous administration of 4.0 mg of NTG as 4 separate hourly injections of 1.0 mg each, affecting the dose-dependent response of NTG IV injection. The 4 high-dose NTG pulse injections produced a marked shift in the dose—response curves for arterial pressure depression induced by intravenous injection of the challenge doses of NTG, but did not alter hypotensive responses to sodium nitroprusside. The tolerance responses to arterial pressure depression were enhanced by a bilateral microinjection of NTG (1 nmol) and by diethylamine NONOate (1 nmol), an NO donor, into the posterior hypothalamus. Bilateral microinjection of guanethidine (1.5 nmol), a noradrenergic blocker, into the posterior hypothalamus inhibits NTG tolerance in a period of time within 2 hours. We conclude that exogenous NO and noradrenergic activation in the posterior hypothalamus play an important role in arterial pressure tolerance to systemically administered NTG.
The Rockwood Preparatory Program for Sexual Offenders
Authors: Marshall L.E. , Marshall W.L. , Fernandez Y.M. , Malcolm P.B. , Moulden H.M.
Published: March 2008

This article describes the Rockwood Preparatory Program for sexual offenders. This program operates in the Millhaven induction center of the Correctional Service of Canada. Clients remain in the program for 6 to 8 weeks, depending on when they are placed in their home prison, where they will receive a full treatment program. The preparatory program takes a motivational approach, integrating several theoretical views and employing the therapeutic approaches that have been shown to maximize effectiveness with sexual offenders. The content and approach of the program are described and the observed benefits are outlined.
The Relationship Between Victim Age and Gender Crossover Among Sex Offenders
Authors: Levenson Jill S. , Becker Jennifer , Morin John W.
Published: March 2008

Some child molesters abuse children of both genders. The purpose of this study was to explore the relationship between gender crossover and victim age. The authors hypothesized that offenders who molested children of both genders would be more likely to have very young victims and that offenders who molested very young children would be more likely to abuse children of both sexes than offenders with older victims. The sample consisted of 362 sex offenders being considered for civil commitment as sexually violent predators in Florida. Data were collected from file reviews. The relationship between victim age and gender crossover was examined using chi-square and multivariate logistic regression analyses. The proportion of offenders with victims of both genders significantly increased as the victims' ages decreased, and sex offenders with preschool-age victims were most likely to have abused both boys and girls. A sex offender with a victim 6 years of age or younger had more than 3 times the odds of having perpetrated sex crimes against both genders than a sex offender with only older victims. Sex offenders with victims of both genders had more than 3 times the odds of having preschool victims. The presence of a major mental illness increased the odds of gender crossover more than threefold. Pedophilia increased the odds of having victims younger than 6 more than 11-fold. Implications for practice are discussed.
Parental Investment, Club Membership, and Youth Sexual Risk Behavior in Cape Town
Authors: Camlin Carol S. , Snow Rachel C.
Published: March 2008

This study examines whether parental investment and membership in social clubs are associated with safer sexual behaviors among South African youth. Participants comprised 4,800 randomly selected adolescents age 14 to 22 living in the Cape Town area in 2002. Logistic regression was used to examine associations between measures of parental investment and associational membership with reported condom use at first and most recent sexual intercourse, net of effects of HIV knowledge, age, education, population group, parental coresidence, and household income. Interaction terms were used to examine gender differences in associations between risk behavior and parental investment and between risk behavior and group membership. Participation in clubs and community groups is associated with safer behaviors. A mother's financial support (for clothing, school fees and uniforms, and pocket money) is negatively associated with condom use, particularly among young women, suggesting that material need impels vulnerability to higher risk behaviors. Social resources in households and communities mediate HIV risk behaviors among youth in Cape Town.
Atypical ischemic lower extremity ulcerations: a differential diagnosis
Authors: Dean Steven M
Published: March 2008

Abstract

Severe peripheral artery disease (PAD) is the predominant cause of ischemic ulcerations involving the lower extremities. PAD-associated ulcerations are typically distally located involving the feet, toes, and sometimes the calves. In contradistinction, atypical ischemic ulcerations of the lower extremity are often non-atherosclerotic in etiology, involve the proximal leg (thigh/buttocks), can evolve despite palpable distal pulses, and may coexist with other cutaneous aberrations (e.g. macules, purpura, nodules, and livedo reticularis). A differential diagnosis of atypical ischemic ulcerations involving the legs is presented.
C-reactive protein, anti-C-reactive protein antibodies and clinical atherosclerosis
Authors: Rosenau Barbara J , Costenbader Karen H , Schur Peter H
Published: March 2008

Abstract

There has been considerable interest in the relationship between C-reactive protein (CRP) and atherosclerosis. We have previously demonstrated that individuals, especially those with rheumatoid arthritis and systemic lupus erythematosus, may produce antibodies to CRP. This study was therefore undertaken to determine the possible association between anti-CRP antibodies and atherosclerosis. A total of 103 individuals were identified with or without atherosclerosis, and without clinical rheumatic diseases. They were evaluated with respect to cholesterol, HDL, LDL, high-sensitivity (hs)CRP, and anti-CRP antibody levels, as well as use of statin medications. Individuals with atherosclerosis were much more likely to be taking a statin, and thus have lower lipid levels. However, there was no association between hsCRP or anti-CRP antibody levels with atherosclerosis, statin use, or each other. These observations suggest that anti-CRP antibody is not involved in atherosclerosis, and may represent an epiphenomenon.
Fibromuscular dysplasia of the internal carotid circulation: an unusual presentation
Authors: Bhuriya Rohitkumar , Arora Rohit , Khosla Sandeep
Published: March 2008

Abstract

Fibromuscular dysplasia (FMD) is an arterial disease of unknown etiology. Most often it affects the renal and internal carotid arteries (ICA), although any artery can be involved. Internal carotid arteries are affected in 25–30% of patients. When carotid arteries are involved, cervical segments C1-C2 are most often affected. FMD of intracranial arteries is rare. FMD has been associated with intracranial aneurysms in 7–50% cases, but FMD associated with a giant (> 2.5 cm) intracranial aneurysm is rare. Extracranial internal carotid aneurysms are uncommon, with only 3% caused by FMD. We report a case of intra and extracranial FMD associated with a giant intracranial aneurysm and an aneurysm of the right extracranial ICA.
Over-expression of GTP-cyclohydrolase 1 feedback regulatory protein attenuates LPS and cytokine-stimulated nitric oxide production
Authors: Nandi Manasi , Kelly Peter , Vallance Patrick , Leiper James
Published: March 2008

Abstract

GTP-cyclohydrolase 1 (GTP-CH1) catalyses the first and rate-limiting step for the de novo production of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase (NOS). The GTP-CH1-BH4 pathway is emerging as an important regulator in a number of pathologies associated with over-production of nitric oxide (NO) and hence a more detailed understanding of this pathway may lead to novel therapeutic targets for the treatment of certain vascular diseases. GTP-CH1 activity can be inhibited by BH4 through its protein–protein interactions with GTP-CH1 regulatory protein (GFRP), and transcriptional and post-translational modification of both GTP-CH1 and GFRP have been reported in response to proinflammatory stimuli. However, the functional significance of GFRP/GTP-CH1 interactions on NO pathways has not yet been demonstrated. We aimed to investigate whether over-expression of GFRP could affect NO production in living cells. Over-expression of N-terminally Myc-tagged recombinant human GFRP in the murine endothelial cell line sEnd 1 resulted in no significant effect on basal BH4 nor NO levels but significantly attenuated the rise in BH4 and NO observed following lipopolysaccharide and cytokine stimulation of cells. This study demonstrates that GFRP can play a direct regulatory role in iNOS-mediated NO synthesis and suggests that the allosteric regulation of GTP-CH1 activity by GFRP may be an important mechanism regulating BH4 and NO levels in vivo.
Health Perceptions of Latinos With Intellectual Disabilities: The Results of a Qualitative Pilot Study
Authors: Jurkowski Janine M. , Rivera Yesenia , Hammel Joy
Published: March 2008

A pilot study among Latinos with intellectual disabilities (ID) was conducted. Focus groups and Photovoice methodology were employed to explore participants' health perceptions and beliefs. Three focus groups were conducted for a total of 15 participants. An additional member check focus group was conducted to verify results of the analysis. Photovoice methodology was employed with four Latinos with ID to explore health beliefs and perceptions of the influence of the social and physical environment. Participants' perceptions of health focused on social and mental aspects of health. Latinos with ID believed that social relationships are important to health. They believed in a connection among social, mental, and physical well-being and health. Cultural beliefs related to the role of God and traditional therapies were identified. Latinos with ID reported that they believed that health was influenced by behaviors and that diet and physical activity were beneficial, but this did not necessarily translate into regular practice.
Survey Design From the Ground Up: Collaboratively Creating the Toronto Teen Survey
Authors: Flicker Sarah , Guta Adrian , Larkin June , Flynn Susan , Fridkin Alycia , Travers Robb , Pole Jason D. , Layne Crystal
Published: March 2008

The Toronto Teen Survey is a community-based participatory research study whose aim is to gather information on the accessibility and relevance of sexual health services for diverse groups of urban youth (13 to 17 years of age). This information will be used to develop a proactive, citywide strategy to improve sexual health outcomes for Toronto adolescents. In this article, the authors focus on the processes of collaboratively developing a survey tool with youth, academics, and community stakeholders. An overview of the project and examples from the design stage are provided. In addition, recommendations are given toward developing best practices when working with young people on research and survey design.
Fan Substitution and the 2004-05 NHL Lockout
Authors: Winfree Jason A. , Fort Rodney
Published: March 2008

This study estimates fan substitution in sports using the 2004-05 National Hockey League (NHL) season-long lockout as a natural experiment. The authors find that NHL fans substitute minor league and junior league hockey for the NHL. Because this is not due to a change in the price of a substitute good, the findings point to pure substitution effects without income effects. The findings have implications for future work on fan demand, especially for those studying habit and loyalty, or sports policy.
Toward the Employability—Link Model: Current Employment Transition to Future Employment Perspectives
Authors: Thijssen Johannes G.L. , Van der Heijden Beatrice I.J.M. , Rocco Tonette S.
Published: March 2008

This article goes into a critical analysis of the concept of employability, its development across historical periods, its components, and different strategic approaches to enhance workers' employability throughout their career. Given the need for a systematic analysis and more empirical research in the field, the authors come up with the so-called employability—link model that is aimed to guide future practitioners and researchers as far as their specific choices as regard core components of the concept that ought to be made. The article concludes with a thorough onset of possible future research questions that are assumed to be of importance given the current labor market situation. The employability—link model has implications for individual and organizational career interventions aimed at increasing life-long employability.
Integrative Literature Review: Workplace Incivility: Impacts on Individual and Organizational Performance
Authors: Estes Brad , Jia Wang
Published: March 2008

Although workplace incivility has been found to negatively impact individual and organizational performance and interfere with the creation of a civil and respectful workplace, the phenomenon has been largely overlooked by the field of human resource development (HRD). This article reviewed the workplace incivility literature to provide a better understanding of the characteristics, prevalence, trends, causes, and impacts of this phenomenon in contemporary workplaces. The review indicates that workplace incivility frequently occurs and is harmful; however, it is generally not well understood and accordingly not recognized as an issue needing attending. Therefore, this article calls for research attention from HRD scholars. The authors further provide HRD practitioners some guidelines that may assist them in identifying and dealing with uncivil behaviors at work and ultimately bringing out the desired individual and organizational performance.
Multidrug-Resistant Enterococcus raffinosus From A Decubitus Ulcer: A Case Report
Authors: Savini Vincenzo , Manna Assunta , Di Bonaventura Giovanni , Catavitello Chiara , Talia Marzia , Balbinot Andrea , Febbo Fabio , D'Antonio Domenico
Published: March 2008

A case of decubitus ulcer infected with multidrug-resistant Enterococcus raffinosus is reported in this article. This is the first report of wound infection caused by an Enterococcus raffinosus isolate resistant to antibiotics other than β-lactams, gentamicin, and ciprofloxacin. This case adds to the knowledge base concerning the onset of antibiotic resistance in this uncommon species and confirms the emerging role of daptomycin as a promising alternative in therapy of severe difficult-to-treat enterococcal infections.
Fusarium solani in the Post-transplant Patient: An Unusual Fungus
Authors: Rekha Arcot , Kindo Anupma J. , Ravi Annamalai
Published: March 2008

The incidence of fungal infections in post-transplant patients ranges from 2% to 50%, and more uncommon pathogens are being isolated. Earlier, the fungi seen were candida, aspergillus, and cryptococcus; and of late, histoplasma, coccidiodomycoses, and dematiaceous fungi are seen. In this article, a patient with invasive fusariosis is presented, and literature of this uncommon fungus is reviewed.
Seminar Review: Wounds and Dressings
Authors: van den Bulck Rosine
Published: March 2008

Venous leg ulcers are the most common type of lower limb ulceration. Compression therapy combined with the use of appropriate dressings remain the gold standard for the management of venous ulcers. Although a wide range of wound dressings is available, the management of venous leg ulcers is primarily dependent on a careful assessment of the patient, the wound, and the effectiveness of the treatment.
MRSA Infection in Lower Extremity Wounds
Authors: Edris Bree , Reed James F.
Published: March 2008

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most frequently isolated bacteria in wound cultures. MRSA has been linked to lengthened wound healing times, an increase in adverse postoperative outcomes, and mortality. This study investigated the incidence of MRSA in lower extremity wounds and examined outcomes associated with MRSA-infected wounds versus non-MRSA-infected wounds. A retrospective study was conducted. Patients with MRSA-infected wounds were compared with those with uninfected wounds in a 1:2 ratio. Demographics, infection, and stay information were collected. Data were analyzed using SPSS 15.0. 51 patients were included (17 with MRSA and 34 without MRSA). Patients with MRSA had increased lengths of stay and a higher incidence of adverse postoperative outcomes compared with non-MRSA patients. An MRSA infection adversely affects a patient's hospital course. Preoperative screening for MRSA and postoperative surveillance should be considered to prevent and eliminate the spread of this virulent bacterium.
Examining Strain in a School Context
Authors: Lee Daniel R. , Cohen Jeffrey W.
Published: March 2008

General strain theory has accumulated a considerable amount of empirical support. Many of these assessments have tested the direct relationship that strain has on crime and delinquency. The research presented here examines the relationship between schools and delinquency within a general strain theory perspective. More specifically, this research examines how schools can not only act as a source of an individual's strain and subsequent delinquency but also be a source for mediating or coping with strain and minimizing delinquency. To test the relationship between schools and delinquency, data from the National Educational Longitudinal Survey (NELS:88) are analyzed in a model of general strain that specifies sources of school-based strain and sources of school-based mechanisms for controlling strain.
Adolescent Sexual Victimization
Authors: Stein Rachel E. , Nofziger Stacey D.
Published: March 2008

This study investigates the experience of sexual victimization among American youth. The objective is to determine who adolescents tell of their victimization and whether the choice of confidant influences the likelihood of the offender being arrested. Using data from the 1995 National Survey of Adolescents, the authors found that most adolescents do not turn to official sources but instead tell family members and friends about their sexual victimization. Although only 13% of sexual assault disclosures resulted in an arrest of the offender, arrest was more likely to occur when the assault was initially reported to the victim's mother. A much less common choice of confidant was mandatory reporters, professionals in contact with children who are required by law to report suspected and known child abuse. However, when mandatory reporters were informed, they were not consistent in reporting the offense to officials. Therefore, the authors suggest mandatory reporters are not offering the necessary support to adolescent victims of sexual abuse.
The Truth About Baby Boomer Gamers
Authors: Pearce Celia
Published: March 2008

This article describes a study conducted in the summer of 2006 aimed at exploring the play patterns and lifestyles of gamers who fall into the loose demographic of “Baby Boomers,” typically defined as people born between 1946 and 1964. This independent study, including more than 300 participants, combined quantitative and qualitative techniques to paint a multifaceted picture of the gaming lifestyles and tastes of this understudied population. The study findings show that Baby Boomers comprise a vibrant video game audience, that they are devoted players, and that they have distinct needs and interests that have gone ignored by both the mainstream game industry and the game press. They also provide some detailed data about their play styles and gaming interests, the role of gaming in their larger media mix, as well as specific case studies that paint a nuanced portrait of this understudied and underserved audience.
Integrative Mixed Methods Data Analytic Strategies in Research on School Success in Challenging Circumstances
Authors: Jang Eunice E. , McDougall Douglas E. , Pollon Dawn , Herbert Monique , Russell Pia
Published: March 2008

There are both conceptual and practical challenges in dealing with data from mixed methods research studies. There is a need for discussion about various integrative strategies for mixed methods data analyses. This article illustrates integrative analytic strategies for a mixed methods study focusing on improving urban schools facing challenging circumstances. The research was conducted using a concurrent mixed methods approach. The qualitative and quantitative strands of data were analyzed independently through thematic analysis of qualitative data and factor analysis of survey data, followed by integrative data analytic procedures. The integrative data analytic approach included strategies such as parallel integration for member checking, data transformation for comparison, data consolidation for emergent themes, and case analysis for fine-grained descriptions of school profiles. The integrative data analysis process featured the iterative nature of mixing data sources at various points and allowed the researchers to pay attention to emergent insights made available through mixed methods research.
The phylogeny of the mammalian heme peroxidases and the evolution of their diverse functions
Authors: Loughran Noeleen B , O'Connor Brendan , Ó'Fágáin Ciarán , O'Connell Mary J
Published: March 2008

Background

The mammalian heme peroxidases (MHPs) are a medically important group of enzymes. Included in this group are myeloperoxidase, eosinophil peroxidase, lactoperoxidase, and thyroid peroxidase. These enzymes are associated with such diverse diseases as asthma, Alzheimer's disease and inflammatory vascular disease. Despite much effort to elucidate a clearer understanding of the function of the 4 major groups of this multigene family, we still do not have a clear understanding of their relationships to each other.

Results

Sufficient signal exists for the resolution of the evolutionary relationships of this family of enzymes. We demonstrate, using a root mean squared deviation statistic, how the removal of the fastest evolving sites aids in the minimisation of the effect of long branch attraction and the generation of a highly supported phylogeny. Based on this phylogeny we have pinpointed the amino acid positions that have most likely contributed to the diverse functions of these enzymes. Many of these residues are in close proximity to sites implicated in protein misfolding, loss of function or disease.

Conclusion

Our analysis of all available genomic sequence data for the MHPs from all available completed mammalian genomes, involved sophisticated methods of phylogeny reconstruction and data treatment. Our study has (i) fully resolved the phylogeny of the MHPs and the subsequent pattern of gene duplication, and (ii), we have detected amino acids under positive selection that have most likely contributed to the observed functional shifts in each type of MHP.
Improved detection of global copy number variation using high density, non-polymorphic oligonucleotide probes
Authors: Shen Fan , Huang Jing , Fitch Karen R , Truong Vivi B , Kirby Andrew , Chen Wenwei , Zhang Jane , Liu Guoying , McCarroll Steven A , Jones Keith W , Shapero Michael H
Published: March 2008

Background

DNA sequence diversity within the human genome may be more greatly affected by copy number variations (CNVs) than single nucleotide polymorphisms (SNPs). Although the importance of CNVs in genome wide association studies (GWAS) is becoming widely accepted, the optimal methods for identifying these variants are still under evaluation. We have previously reported a comprehensive view of CNVs in the HapMap DNA collection using high density 500 K EA (Early Access) SNP genotyping arrays which revealed greater than 1,000 CNVs ranging in size from 1 kb to over 3 Mb. Although the arrays used most commonly for GWAS predominantly interrogate SNPs, CNV identification and detection does not necessarily require the use of DNA probes centered on polymorphic nucleotides and may even be hindered by the dependence on a successful SNP genotyping assay.

Results

In this study, we have designed and evaluated a high density array predicated on the use of non-polymorphic oligonucleotide probes for CNV detection. This approach effectively uncouples copy number detection from SNP genotyping and thus has the potential to significantly improve probe coverage for genome-wide CNV identification. This array, in conjunction with PCR-based, complexity-reduced DNA target, queries over 1.3 M independent NspI restriction enzyme fragments in the 200 bp to 1100 bp size range, which is a several fold increase in marker density as compared to the 500 K EA array. In addition, a novel algorithm was developed and validated to extract CNV regions and boundaries.

Conclusion

Using a well-characterized pair of DNA samples, close to 200 CNVs were identified, of which nearly 50% appear novel yet were independently validated using quantitative PCR. The results indicate that non-polymorphic probes provide a robust approach for CNV identification, and the increasing precision of CNV boundary delineation should allow a more complete analysis of their genomic organization.
Evolution of DC-SIGN use revealed by fitness studies of R5 HIV-1 variants emerging during AIDS progression
Authors: Borggren Marie , Repits Johanna , Kuylenstierna Carlotta , Sterjovski Jasminka , Churchill Melissa J , Purcell Damian FJ , Karlsson Anders , Albert Jan , Gorry Paul R , Jansson Marianne
Published: March 2008

Background

At early stages of infection CCR5 is the predominant HIV-1 coreceptor, but in approximately 50% of those infected CXCR4-using viruses emerge with disease progression. This coreceptor switch is correlated with an accelerated progression. However, those that maintain virus exclusively restricted to CCR5 (R5) also develop AIDS. We have previously reported that R5 variants in these "non-switch virus" patients evolve during disease progression towards a more replicative phenotype exhibiting altered CCR5 coreceptor interactions. DC-SIGN is a C-type lectin expressed by dendritic cells that HIV-1 may bind and utilize for enhanced infection of T cells in trans. To further explore the evolution of the R5 phenotype we analyzed sequential R5 isolates obtained before and after AIDS onset, i.e. at the chronic stage and during end-stage disease, with regard to efficiency of DC-SIGN use in trans-infections.

Results

Results from binding and trans-infection assays showed that R5 viruses emerging during end-stage AIDS disease displayed reduced ability to use DC-SIGN. To better understand viral determinants underlying altered DC-SIGN usage by R5 viruses, we cloned and sequenced the HIV-1 env gene. We found that end-stage R5 viruses lacked potential N-linked glycosylation sites (PNGS) in the gp120 V2 and V4 regions, which were present in the majority of the chronic stage R5 variants. One of these sites, amino acid position 160 (aa160) in the V2 region, also correlated with efficient use of DC-SIGN for binding and trans-infections. In fitness assays, where head-to-head competitions between chronic stage and AIDS R5 viruses were setup in parallel direct and DC-SIGN-mediated infections, results were further supported. Competitions revealed that R5 viruses obtained before AIDS onset, containing the V2 PNGS at aa160, were selected for in the trans-infection. Whereas, in agreement with our previous studies, the opposite was seen in direct target cell infections where end-stage viruses out-competed the chronic stage viruses.

Conclusion

Results of our study suggest R5 virus variants with diverse fitness for direct and DC-SIGN-mediated trans-infections evolve within infected individuals at end-stage disease. In addition, our results point to the importance of a glycosylation site within the gp120 V2 region for efficient DC-SIGN use of HIV-1 R5 viruses.
Wnt7b stimulates embryonic lung growth by coordinately increasing the replication of epithelium and mesenchyme
Authors: Rajagopal Jayaraj , Carroll Thomas J. , Guseh J. Sawalla , Bores Sam A. , Blank Leah J. , Anderson William J. , Yu Jing , Zhou Qiao , McMahon Andrew P. , Melton Douglas A.
Published: March 2008

The effects of Wnt7b on lung development were examined using a conditional Wnt7b-null mouse. Wnt7b-null lungs are markedly hypoplastic,yet display largely normal patterning and cell differentiation. In contrast to findings in prior hypomorphic Wnt7b models, we find decreased replication of both developing epithelium and mesenchyme, without abnormalities of vascular smooth muscle development. We further demonstrate that Wnt7b signals to neighboring cells to activate both autocrine and paracrine canonical Wnt signaling cascades. In contrast to results from hypomorphic models, we show that Wnt7b modulates several important signaling pathways in the lung. Together, these cascades result in the coordinated proliferation of adjacent epithelial and mesenchymal cells to stimulate organ growth with few alterations in differentiation and patterning.
CD14 and TLR4 are expressed early in tammar (Macropus eugenii)neonate development
Authors: Daly Kerry A. , Lefévre Christophe , Nicholas Kevin , Deane Elizabeth , Williamson Peter
Published: March 2008

Marsupials are born in a relatively underdeveloped state and develop during a period of intensive maturation in the postnatal period. During this period,the young marsupial lacks a competent immune system, but manages to survive despite the potential of exposure to environmental pathogens. Passive immune transfer via the milk is one well-recognised strategy to compensate the neonate, but there also may be innate immune mechanisms in place. In this study, CD14 and Toll-like receptor 4 (TLR4), integral molecular components of pathogen recognition, were identified and characterised for the first time in a marsupial, the tammar wallaby (Macropus eugenii). Functional motifs of tammar CD14 and the toll/interleukin receptor (TIR) domain of TLR4 were highly conserved. The lipopolysaccharide (LPS) binding residues and the TLR4 interaction site of CD14 were conserved in all marsupials. The TIR signalling domain had 84% identity within marsupials and 77% with eutherians. Stimulation of adult tammar leukocytes resulted in the induction of a biphasic pattern of CD14 and TLR4 expression, and coincided with increased production of the pro-inflammatory cytokine TNF-α. Differential patterns of expression of CD14 and TLR4 were observed in tammar pouch young early in development,suggesting that early maturation of the innate immune system in these animals may have developed as an immune survival strategy to protect the marsupial neonate from exposure to microbial pathogens.
Ethical and governance challenges in human fetal tissue research
Authors: Woods S , Taylor K
Published: March 2008

Genetics holds the key to understanding normal human biology and possibly many of the major causes of human disease and impairment. Research into human developmental genetics seems, therefore, to be both necessary and justified. However, such research requires the use of embryonic and fetal tissue obtained from spontaneous abortions and elective termination of pregnancy. This paper examines the arguments in favour of using tissue from elective terminations and the evolution of regulatory frameworks for this research. The paper argues that the recent statutory and regulatory reforms in the UK have not properly addressed the issue of ethically obtaining postimplantation human embryos for research. It is argued that the recent reforms have left the Polkinghorne guidelines untouched but that these are now unequal to the task. A practical suggestion for reform of the approach to the informing and consent of potential donors is offered.
Views regarding physician-assisted suicide: a study of medical professionals at various points in their training
Authors: Kitching Mark , Stevens Andrew James , Forman Louise
Published: March 2008

In this study, we sought to obtain detailed opinion on some of the practical issues that might arise should physician-assisted suicide (PAS) ever be legalized in the UK. We carried out an anonymous postal questionnaire of medical students, junior and senior doctors working at an acute hospital trust, over a three-week period. A total of 435 questionnaires were distributed and we had an overall return rate of 34%. We found that opinions changed very little as doctors progressed from medical school through to senior clinical positions. Overall, there was neutral opinion on whether PAS should be legalized. There was strong support for a multidisciplinary approach to the process and the involvement of the coroner. An opt-out clause for physicians who did not want to be involved in assisted suicide also received strong support.
Institutional ethics committees: lessons from the Royal College of Physicians?
Authors: Saunders John
Published: March 2008

Some health-care institutions have ethics committees. The experience of the Ethical Issues Committee at the Royal College of Physicians is described. Ethics committees in institutions may be reactive or creative, must determine an agenda and must deal with dissent.
The withholding of truth when counselling relatives of the critically ill: a rational defence
Authors: Berry Philip A
Published: March 2008

In cases of sudden, life-threatening illness where the chance of survival appears negligible to the admitting physician, this opinion is not always revealed during the initial meeting with the patient's relatives. Reasons as to why this withholding of the truth may be acceptable are explored through review of available evidence and personal reflection. Factors identified include: the importance of hope in families' coping mechanisms, and the instinct to preserve it; the fallibility of physicians' perception of poor prognosis in the early phase of illness; the need to avoid large swings in relatives' expectations that occur when patients appear to rally during initial resuscitation; and the adverse effect that an atmosphere of hopelessness can have on the provision of medical care. A strategy for the staged disclosure of information and the confirmation of hopelessness is then described, the aim being to find a compromise between providing a true opinion about a patient's prognosis, and regard for the opposing factors described.
Social comparison activity in coping with HIV
Authors: Derlega Valerian J , Greene Kathryn , Henson James M , Winstead Barbara A
Published: March 2008

Summary

Taylor and Lobel's (1989) model of social comparison processes under threat predicts that upward affiliation (a social activity) may be useful to improve the skills and to find inspiration in coping with HIV, whereas downward evaluation (a cognitive activity) may assist someone to feel better by comparing oneself to a less fortunate person. Participants with HIV were randomly assigned, using a 3 × 3 factorial design, to read one of nine vignettes about someone whose HIV medical prognosis and psychological adjustment were described as good, poor or unspecified. Participants desired upward affiliation with a target doing well physically, but they wanted to avoid a target doing poorly psychologically. Participants also evaluated their own physical condition as better than a target coping poorly physically with HIV. The results may be useful in understanding the impact of various role models in coping with HIV.
Preferred options for receiving sexual health screening results: a population and patient survey
Authors: Brown L , Copas A , Stephenson J , Gilleran G , Ross J D C
Published: March 2008

Summary

Current genitourinary medicine patients (202) and potential future patients (542) completed a questionnaire-based survey to determine their preference for obtaining test results, their acceptability of including a named infection on contact slips and to report expectations about the acceptable length of an appointment. Overall, most respondents (78% [n = 582]) felt it unacceptable to be only contacted if their results were positive (‘no news is good news’). In the clinic, a majority preferred a contact slip to be coded (68% [n = 137]), in the general public views were balanced. Significantly, more people in the general population expected an appointment to last no longer than 30 min (32% [n = 173] cf. 10% [n = 21], P < 0.001). A clear preference was expressed to receive sexually transmitted infection test results even if they are negative. Telephone and face-to-face contact were most popular with relatively few choosing mobile telephone text messaging or email as their preferred option.
Asymptomatic urethral infection in male sexually transmitted disease clinic attendees
Authors: Yu J T H T , Tang W Y M , Lau K H , Chong L Y , Lo K K
Published: March 2008

Summary

The purpose of this study is to determine the prevalence of asymptomatic male patients with urethral infections attending a government sexually transmitted infection clinic in Hong Kong and their microbiological profile. A total of 274 consecutive male patients without any symptoms for urethral infections were recruited. A questionnaire was used to record the symptoms, sexual history and demographics. Further assessment, including urethral smear for Gram stain, gonococcal culture and polymerase chain reaction (PCR) for Chlamydia trachomatis (CT), Mycoplasma genitalium (MG) and Ureaplasma urealyticum (UU) were performed.

In 274 asymptomatic patients, 36 patients had non-gonococcal urethritis (NGU) and two patients had positive gonoccocal culture. Among the asymptomatic patients with NGU, there were 6 (16.6%), 10 (22.8%) and five (13.9%) patients with positive PCR for CT, UU and MG, respectively. In addition, there were 14 asymptomatic patients with positive PCR for CT but without evidence of NGU. In conclusion, urethral infections were identified in a significant number of asymptomatic male patients and therefore, routine screening for this group is warranted.
Occult hepatitis B virus infection in HIV-infected Lebanese patients with isolated antibodies to hepatitis B core antigen
Authors: Ramia S , Mokhbat J , Ramlawi F , El-Zaatari M
Published: March 2008

Summary

The presence of hepatitis B virus (HBV) serological markers have been investigated in 101 Lebanese patients (69 men, 32 women; mean age 32.7 ± 1.7 years) infected with human immunodeficiency virus type 1 (HIV-1). Seven patients (6.9%) were HBsAg carriers compared with 54 patients (53.5%) who had no evidence of exposure to HBV infection. Twenty-four patients (23.8%) had anti-HBc alone as a serological marker compared with four patients who were positive for anti-HBs alone and 12 patients (11.9%) who were anti-HBc and anti-HBs-positive. Occult HBV infection (presence of HBV DNA in the absence of HBsAg) is found to be relatively high (28.7%) in HIV-infected Lebanese patients and the overwhelming majority (83.3%) of those who were positive for anti-HBc alone had a detectable HBV DNA in their serum. However, none of our HIV-positive patients with occult HBV infection had abnormal alanine aminotrasferase level, which also raises the question as to whether occult HBV plays a role in the aetiology of liver disease in HIV-infected patients. Further, studies on the association between HBV DNA levels and markers of liver function in addition to data on liver biopsy would help in answering this question.
Venous tonus enhancement after a short cycle of intermittent pneumatic compression
Authors: Harfouche J N , Theys S , Hanson P , Schoevaerdts J C , Sturbois X
Published: March 2008

Objectives

To test if intermittent pneumatic compression (IPC) used with a short cycle could reproduce and confirm the 30 min vasoconstriction effect observed after a long cycle of pressure.

Methods

Eighteen subjects took part in the study, 12 with venous insufficiency (VI) and six without VI (NonVI). Duplex scanner was used to evaluate the diameter of six sites of veins on each of both lower limbs before and after the treatment. The IPC was applied to only one limb.

Results

The control limb showed no change in venous diameter. The treated limb, showed in the NonVI group one vasoconstriction: the greater saphena at the knee level (GS) ( P < 0.05). In the VI group, four sites out of six showed a vasoconstriction: the common femoral ( P < 0.005), the GS at its cross ( P < 0.001), the GS ( P < 0.001) and the lesser saphena ( P < 0.05).

Conclusions

Both long and short cycle of IPC are suitable to enhance the venous tone in VI patients for at least 30 min after the end of the treatment.
Superficial venous interventions: assessing the risk of DVT
Authors: Vedantham S
Published: March 2008

Objectives

Understand the potential consequences of deep vein thrombosis (DVT) in patients undergoing superficial venous interventions, the proper way to assess DVT risk in patients with superficial venous disease and the appropriate management of patients stratified by risk level.

Methods

Review of published literature

Results

Because DVT can have major long-term consequences, DVT risk should be assessed as a routine part of the preprocedure evaluation of venous disease. Chronic venous disease may have multiple contributing factors amenable to treatment in both the superficial and deep venous systems.

Conclusion

Superficial venous interventions should be deferred in patients at particularly high risk for DVT, but may be performed with appropriate countermeasures for DVT prophylaxis in patients at moderate risk.