bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relation Between Comprehensive Assessment Procedures and Diagnostic Stability in School-Aged Children Identified With Learning Disabilities
Authors: Rosenblum Yonatan , Larochette Anne-Claire , Harrison Allyson G. , Armstrong Irene
Published: December 2009

Learning Disabilities (LDs) affect a significant number of students in elementary and secondary school. In order for these students, along with parents and teachers, to understand the nature of their specific difficulties, and have equal opportunity in academic settings, a comprehensive psychological report containing properly informed recommendations for accommodations must be provided. In the present study, previous psychological assessment reports of 100 Grade 7 and 8 LD identified students were evaluated based on gold standard criteria. Previous and current diagnoses were compared to test the hypothesis that less comprehensive previous assessment reports would be significantly associated with a change in diagnosis between assessments. This hypothesis was supported. In addition, many previous reports did not use a complete battery of tests or have a clear diagnostic statement. It was found that the various types of practitioners conducting preliminary assessments were a significant cause for disparity between reports. Recommendations for improved early diagnostic practices are discussed.
Acute Transient Deafness Representing a Negative Epileptic Phenomenon
Authors: Shahar Eli , Ravid Sarit , Genizi Jacob , Schif Aharon
Published: December 2009

We report herein 2 children who presented with acute deafness heralding an epileptic event manifesting thereafter by loss of consciousness and tonic generalized posturing, possibly reflecting a negative epileptic phenomenon. The first previously healthy male had 2 paroxysmal episodes 7 months apart, starting with acute deafness lasting for a few minutes followed by loss of consciousness and generalized tonic posturing for 10 minutes. Electroencephalography (EEG) during the second episodes demonstrated generalized epileptiform discharges. The second with previously controlled partial complex seizures presented with episodes of complete deafness lasting for a few minutes followed by loss of consciousness and focal tonic posturing lasting 10 minutes. Such acute deafness represented an aura of a focal seizure substantiated by right focal temporal epileptic discharges within the region of the primary auditory cortex. Therefore, EEG should be performed in any case of acute transient deafness, even in the absence of accompanying overt clinical seizures.
Design and Dynamic Culture of 3D-Scaffolds for Cartilage Tissue Engineering
Authors: El-Ayoubi Rouwayda , DeGrandpré Christian , DiRaddo Robert , Yousefi Azizeh-Mitra , Lavigne Patrick
Published: December 2009

Engineered scaffolds for tissue-engineering should be designed to match the stiffness and strength of healthy tissues while maintaining an interconnected pore network and a reasonable porosity. In this work, we have used 3D-plotting technique to produce poly-L-Lactide macroporous scaffolds with two different pore sizes. The ability of these macroporous scaffolds to support chondrocyte attachment and viability were compared under static and dynamic loading in vitro. Moreover, the 3D-plotting technique was combined with porogen-leaching, leading to macro/microporous scaffolds, so as to examine the effect of microporosity on the level of cell attachment and viability under similar loading condition.

Canine chondrocytes’ cells were seeded onto the scaffolds with different topologies, and the constructs were cultured for up to 2 weeks under static conditions or in a bioreactor under dynamic compressive strain of 10% strain, at a frequency of 1 Hz. The attachment and cell growth of chondrocytes were examined by scanning electron microscopy and by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. A significant difference in cell attachment was observed in macroporous scaffolds with different pore sizes after 1, 7, and 14 days. Cell viability in the scaffolds was enhanced with decreasing pore size and increasing microporosity level throughout the culture period. Chondrocyte viability in the scaffolds cultured under dynamic loading was significantly higher (p<0.05) than the scaffolds cultured statically. Dynamic cell culture of the scaffolds improved cell viability and decreased the time of in vitro culture when compared to statically cultured constructs. Optimizing the culture conditions and scaffold properties could generate optimal tissue/constructs combination for cartilage repair.
Occurrence Risk and Structure of Depression in Parkinson Disease With and Without Dementia: Results From the GEPAD Study
Authors: Riedel Oliver , Heuser Isabella , Klotsche Jens , Dodel Richard , Wittchen Hans-Ulrich ,   GEPAD Study Group
Published: December 2009

Background: This study examined the age- and gender-specific risk of depression in demented and non-demented participants, its symptom structure, and associated clinical factors in a nationwide random sample of n = 1449 outpatients with Parkinson disease (PD). Methods: Depression ratings were based on a cross-sectional clinical assessment including the clinical Montgomery-Asberg Depression Rating Scale (MADRS ≥ 14). Parkinson disease severity was rated according to Hoehn and Yahr (HY) and the Unified Parkinson's Disease Rating Scale. Diagnosis of dementia was based on Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition; DSM-IV) criteria. Results: 25.2% (CI: 22.8-27.5) of all patients met study criteria for depression. Additionally, 8.4% of patients did not exceed the MADRS cut-off but were currently being treated with antidepressants, possibly suggesting a corrected (upper limit) total prevalence of 33.6%. Females were more likely depressive than males (29.3% vs 22.4%). In both genders, depression risk was elevated 2- to 4-fold depending on HY stage. Overall, highest rates in non-demented patients were found in females at stages IV to V (53.7%, CI: 37.7-69.6). Demented patients were more likely to meet depression criteria than non-demented (up to 76.2%, 95% CI: 60.5-87.9). Depression symptom profiles for demented PD patients (as compared to non-demented) revealed no structural differences but consistently higher symptom scores. Neither age at onset of PD nor duration of disease were significantly linked with depression. Conclusions: Depression rates are already substantially elevated at early PD stages, emphasizing the need for a thorough examination of mood disorders in all patients with PD. Depression is associated with PD severity and dementia but not with age, age at onset of PD, or disease duration. The differential associations with dementia and the statistical independence of dementia and depression also suggest that depression could not be regarded as a mere demoralisation syndrome.
Cancer Survivorship in Children and Young Adults: A Concept Analysis
Authors: Shepherd Erin J. W. , Woodgate Roberta L.
Published: January 2010

Survivorship has been described in a variety of ways. Understanding how survivorship is applied in the context of childhood cancer survivors is important to the practice of pediatric nursing because it will offer nurses new possibilities for providing guidance, support, and assistance in enhancing outcomes for childhood cancer survivors and their families. Accordingly, the purpose of this article is to provide a conceptual framework that will assist nurses in their efforts to attain the common goal of successful survivorship in childhood cancer survivors. The method of concept analysis developed by Walker and Avant is used. The result is a definition of survivorship that is relevant and useful for research and clinical practice in pediatric oncology.
Coping and Resilience Factors in Pediatric Oncology Nurses CE
Authors: Zander Melissa , Hutton Alison , King Lindy
Published: January 2010

It is well established that pediatric oncology is perceived as a setting that is personally and professionally demanding. Many sources acknowledge the development of conditions, such as burnout, compassion fatigue and vicarious traumatization, as a result of being continuously subjected to highly stressful circumstances in a professional capacity. There are a myriad of individual and collaborative factors that are known to mediate stress in the oncology setting. One such factor is resilience. The purpose of this literature review is to investigate what is known about coping and its relationship with resilience in assisting pediatric oncology nurses to manage work-related stressors. From the themes identified within the reviewed studies, it is clear that the applicability of resilience in pediatric oncology nursing has not been thoroughly investigated. The literature suggests that the presence of resilience among pediatric oncology nurses is possible. What is not known is whether there is a link between this resilience and ability to cope with the stressors of pediatric oncology.
The Undergraduate Case Research Study Model
Authors: Vega Gina
Published: December 2009

Student-written cases are powerful pedagogical tools that can lead to improved understanding of business situations, more informed analysis, emphasis on reflection, and clearer expository writing, all of which are critical skills for business students. Cases provide an opportunity for students to enjoy an active learning experience and derive the experiential payback that such activities offer. In this article, the author describes an innovative method for combining teaching cases and research cases that gives relatively inexperienced undergraduate students practice in applying theory to practice. The project was designed for a small business management class for which the learning objectives go beyond content and theory application; students gain the additional benefits of development of interpersonal skills, an enhanced ability to deal with ambiguity, and the extension of insight and originality. The article provides a design for the implementation of the case-writing process, sample assignments and student work, and theoretical supports that focus on qualitative methodologies. Although the disciplinary focus is small business and entrepreneurship, the process of student case writing can be readily transferred among and beyond business disciplines.
Is Ethnic Diversity Good for the Environment? A Cross-Country Analysis
Authors: Das Jayoti , DiRienzo Cassandra E.
Published: December 2009

Using cross-country data, the major thrust of this study is to establish the existence of a nonlinear relationship between environmental performance and ethnic diversity, while controlling for factors known to affect a country’s ability to meet environmental standards. Using the Environmental Performance Index developed by Columbia and Yale Universities in collaboration with the World Economic Forum, this study finds that countries with moderate levels of ethnic diversity experience the greatest environmental performance as they reap the benefits of a civically engaged society with creative, innovative, and efficient human talent pool and do not bear the negative effects of a highly fractionalized society that typically suffers from poor communication and social cohesion, among other societal ills. The policy implications are important, as policy makers need to understand how ethnic diversity affects a country’s ability to meet environmental goals such that these effects are accounted for in new environmental policies and initiatives.
Getting Cancer Research Into the News: A Communication Case Study Centered on One U.S. Comprehensive Cancer Center
Authors: Clegg Smith Katherine , Friedman Singer Rachel , Edsall Kromm Elizabeth
Published: December 2009

Public dissemination of research findings via the news media has become an important part of the scientific process. The dissemination of complex topics such as cancer has proven somewhat problematic in that news coverage is often judged as compounding, rather than alleviating, communication difficulties. This case study centers around one comprehensive cancer center (CCC) and examines communication stakeholders’ objectives in producing news coverage of cancer issues. The authors’ analysis adopts a constructionist perspective of news making, emphasizing actors’ power to shape news coverage rather than conceptualizing news as a public record of objectively newsworthy events. The authors’ data suggest widespread support for media communication of scientific findings but little articulation of definitive communication goals. It is concluded that without clear articulation of shared goals, communication efforts cannot effectively enhance public empowerment or effectively promote cancer prevention.
Using the Logic Model for Planning and Evaluation: Examples for New Users
Authors: Bucher Julia A.
Published: December 2009

The relationship of tobacco use and many difficult chronic health problems is well—renowned, as are efforts to reduce tobacco product use, and thus, lower the incidence and mortality of tobacco-related disease. Common methods of planning and evaluation, such as logic modeling, in tobacco control initiatives used by public health staff and nongovernmental organizations, are lesser known to health activists in other nations and to direct health care providers in the United States, such as home health administrators, who can mobilize resources to do their part and reduce morbidity from tobacco-related disease. The purpose of this article is to describe basic components of a logic model (LM), its uses for new groups as late adopters, and four common challenges or pitfalls in LM construction with proposed solutions to prevent these problems. An example of elementary synthetic estimation is provided for output calculations and LM examples are given from an international planning workshop for tobacco control that can be used by community-based organizations and home health administrators, new to LM use.
Enticing the New Lad: Masculinity as a Product of Consumption in Tobacco Industry—Developed Lifestyle Magazines
Authors: Cortese Daniel K. , Ling Pamela M.
Published: December 2009

We demonstrate how an industry promoted and defined masculinity as a product of consumption. We analyze previously-secret tobacco industry documents and the content of two tobacco industry—produced magazines, Unlimited (from Philip Morris, makers of Marlboro) and Real Edge (from Brown & Williamson, makers of Lucky Strike), which were distributed to millions of young adult men from the late 1990s and early 2000s to promote their tobacco brands. We find that Unlimited and Real Edge exhibited similar themes previously reported to typify ‘‘new lad’’ magazines, but with risky behaviors in the forefront. We build upon the existing masculinity literature by providing insight into how corporations study and interpret cultural constructions of masculinity, and then use masculinity as both a vehicle and a product of consumption.
Applying Three Strategies for Integrating Quantitative and Qualitative Databases in a Mixed Methods Study of a Nontraditional Graduate Education Program
Authors: Plano Clark Vicki L. , Garrett Amanda L. , Leslie-Pelecky Diandra L.
Published: December 2009

A central issue for mixed methods research is for researchers to effectively integrate (or mix) the quantitative and qualitative data in their studies. Despite extensive methodological discussions about integration, researchers using mixed methods approaches struggle with translating these discussions into practice and often make inadequate use of integration in their studies. The authors examined their integration practices as they applied three literature-based strategies within the context of one mixed methods study about a nontraditional graduate education program. From this examination, the authors describe the processes, products, uses, and challenges that materialized as they merged their quantitative and qualitative databases to develop a better understanding of participants’ perceptions of their experience in the program.
Who Integrated Major League Baseball Faster Winning Teams or Losing Teams? A Comment
Authors: Goff Brian L. , Tollison Robert D.
Published: December 2009

This article offers some comments on recent articles in this journal about the process of racial integration in certain sports venues. Nothing in these articles changes the basic result in an earlier article where the authors show that entrepreneurship by winning teams is the key to understanding which teams integrated first and why.
Specialist Nursing Framework for New Zealand: A Missing Link in Workforce Planning
Authors: Holloway Kathy , Baker Jacqueline , Lumby Judy
Published: December 2009

The current global nursing shortage challenges the provision of a well qualified and sustainable health workforce to meet future population health needs. An identified area of concern for New Zealand reaching health policy targets in chronic conditions management and primary health care is an adequate specialist nurse workforce supply. This article explores the New Zealand context underpinning this concern and contends that effective workforce planning would be supported by the development of a single unified framework for specialist nursing practice in New Zealand. A consistent national framework has the potential to support accurate data collection and enable service providers to identify and plan transparent and transferable pathways for specialist nursing service provision and development. Advanced practice nursing frameworks assist in increasing productivity through building an evidence base about advanced practice, enhancing consistency and equity of expertise; supporting a reduction in role duplication; and enabling succession planning and sustainability.
The Social Significance of Academic Freedom
Authors: Tierney William G. , Lechuga Vicente M.
Published: December 2009

Academic freedom remains a central tenet of our nation’s colleges and universities. However, recent incidents have spawned debates regarding the merits of academic freedom and the mechanism that protects it, tenure. By way of two contrasting examples, the authors consider how two types of higher education institutions—private for-profit universities and nonprofit public institutions—situate themselves in the public dialogue when controversies arise. The authors argue that academic freedom and tenure permit postsecondary institutions to act as vehicles for public engagement, whereas its absence only serves to curtail thoughtful discussions of complex and controversial issues.
Using Coaching to Enhance the Effects of Behavioral Feedback to Managers
Authors: Kochanowski Susan , Seifert Charles F. , Yukl Gary
Published: January 2010

A field experiment was conducted to assess whether coaching would enhance the effectiveness of a feedback workshop for store managers in a regional supermarket chain. The experimental group of managers received individual coaching several weeks after attending a feedback workshop. The control group of managers also attended a feedback workshop but did not receive the follow-up coaching. Each manager’s use of proactive influence tactics was rated by subordinates (department managers) before the interventions and several months afterward. Coaching significantly increased the use of collaboration with subordinates, but results for the other three “core” tactics were mixed. Likely reasons for the lack of stronger results are identified, and implications for practice are discussed.
A Critical Review of the Literature: Engendering the Discourse of Masculinities Matter for Parenting African Refugee Men
Authors: Williams Nombasa
Published: December 2009

According to the literature on culturally and linguistically diverse parenting, refugee parenting practices and styles that are normative in countries of origin may not be sanctioned in Australia. In the case of refugee parenting, beliefs, practices, and values may be decentered in pre-resettlement contexts where survival becomes the primary concern. Engendering the discourse of masculinities to reflect a relationship between child protection and the experience of refugee parenting for African men in both pre- and post-resettlement contexts will inform culturally competent practice, intervention, and community development that is inclusive of their gender-specific needs. This article brings an expanded masculinities perspective to the ecology of refugee parenting for resettled African men resulting from larger research findings with focus group participants. Incorporating notions of masculinity into the child protection discourse is an attempt not only to reduce existing gender under- and misrepresentation among South Australian refugees but also to ensure greater visibility and increase the role of refugee men in the process of developing culturally relevant and appropriate policies, practices, and services to assist successful resettlement transitions while strengthening family well-being. The concept of masculinities, this article argues, must be treated as integral to any approach to working with refugees, particularly in areas that penetrate and may define the quality of their life experiences, expectations, and aspirations. Masculinities matter. Exploring refugee male perceptions, interpretations, and enactment of masculinity may unmask the differential experiences of refugee women from men and ensure the integration and operationalization of these differences into child protection services and practice.
Vibration response imaging (VRI) in lung transplant recipients
Authors: Bodmann Isabelle , Dierich Martin , Fuehner Thomas , Simon Andre , Welte Tobias , Gottlieb Jens
Published: December 2009

Background: In the first 6 months following lung transplantation, the most frequently occurring complications are infection, acute rejection and anastomotic dysfunction. The utility of vibration response imaging (VRI) lung images in assisting with the detection of these complications was evaluated.

Objectives: The study aimed to evaluate if VRI is a good, non-invasive method of detecting clinical problems in lung transplant (LTx) recipients during early follow-up.

Methods: Between 06/2006 and 03/2007 all LTx patients who received transplants during the preceding 6 months at the Hannover Medical School received baseline VRI at enrolment with subsequent reassessment in combination with standard follow-up at 1, 3 and 6 months thereafter. The resulting images were analysed by two blinded reviewers.

Results: Fifty-five lung transplant recipients were enrolled in the study, with 49 patients successfully completing follow-up. Device operability and patient participation occurred without significant problems. High numbers of abnormal scans were detected. According to the clinical diagnosis, 29 patients (59.2 %) were stable at all four visits. Twenty clinical problems occurred (e.g., infections, rejections, obstructions, unknown deterioration). Agreement with clinical interpretation of rejections and infections was poor. Central airway obstruction (CAO) was detected in 80% by both reviewers. Accuracy in detecting obstructions was 89%; positive predicted value and negative predicted value were 80% and 90%, respectively.

Conclusion: The VRI system is a non-invasive easy-to-use method with technical success and good image quality. The high number of abnormal scans makes interpretation following LTx difficult. VRI was unable to detect deterioration in graft function with the exception of ventilation disorders like central airway complications.
Seawater gel in allergic rhinitis: entrapment effect and mucociliary clearance compared with saline
Authors: Cingi Cemal , Halis Unlu H. , Songu Murat , Yalcin Sinasi , Topcu Ismail , Cakli Hamdi , Bal Cengiz
Published: December 2009

Objective: We performed a prospective study to investigate the the efficacy of seawater gel in reducing symptoms in patients with mild allergic rhinitis. We also aimed to investigate the impact of nasal irrigation on mucociliary clearance with seawater gel compared with saline in this patient group.

Methods: The study was performed in 100 consecutive adult individuals with a history of allergic rhinitis that was not controlled by anti-allergic drugs. Patients were assigned to receive seawater gel nasal spray for 10 days. The efficacy of treatment was assessed by means of total nasal symptom score and clinical findings.

Results: A statistically significant difference was found between scores of ‘nasal discharge, nasal obstruction, sneezing, nasal itching’before and after treatment ( p < 0.001). Clinical findings evaluation revealed a statistically significant decrease in lower turbinate colour rating and turbinate congestion at the end of treatment ( p< 0.001). Saccharin transit time decreased from baseline in the seawater trials by 12% compared with a 4% decrease for saline. The difference between the percent changes was statistically significant ( t = 2.177; p < 0.05).

Conclusions: The present study provides evidence that a four times daily regimen of seawater gel can be an adjunctive therapy in the patient with allergic rhinitis.
Stem cell-mediated neovascularization in heart repair
Authors: Nesselmann Catharina , Li Wenzhong , Ma Nan , Steinhoff Gustav
Published: December 2009

Accumulating clinical and experimental evidence indicates that stem cells from various sources are promising in the treatment of cardiac dysfunction. They may be incorporated into neovascular foci and thus contribute to postnatal physiological and pathological vasculogenesis and/or produce a variety of growth factors for angiogenesis and cytokines that home other stem cells from other organs for cardiac regeneration. This review focuses on the neovascularization of stem cells from different sources in cardiac repair, with emphasis on adult stem cells.
Akt1 and Akt2 promote peripheral B-cell maturation and survival
Authors: Calamito Marco , Juntilla Marisa M. , Thomas Matthew , Northrup Daniel L. , Rathmell Jeffrey , Birnbaum Morris J. , Koretzky Gary , Allman David
Published: December 2009

Although the 3 isoforms of Akt regulate cell growth, proliferation, and survival in a wide variety of cell types, their role in B-cell development is unknown. We assessed B-cell maturation in the bone marrow (BM) and periphery in chimeras established with fetal liver progenitors lacking Akt1 and/or Akt2. We found that the generation of marginal zone (MZ) and B1 B cells, 2 key sources of antibacterial antibodies, was highly dependent on the combined expression of Akt1 and Akt2. In contrast, Akt1/2 deficiency did not negatively affect the generation of transitional or mature follicular B cells in the periphery or their precursors in the BM. However, Akt1/2-deficient follicular B cells exhibited a profound survival defect when forced to compete against wild-type B cells in vivo. Altogether, these studies show that Akt signaling plays a key role in peripheral B-cell maturation and survival.
Molecular characterization of in-frame and out-of-frame alternative splicings in coagulation factor XI pre-mRNA
Authors: Asselta Rosanna , Rimoldi Valeria , Guella Ilaria , Soldà Giulia , De Cristofaro Raimondo , Peyvandi Flora , Duga Stefano
Published: December 2009

Alternative splicing of pre-mRNAs is a central process to the generation of proteome complexity. However, many alternative mRNA isoforms carry premature termination codons (PTCs) rendering them possible targets for the nonsense-mediated mRNA decay (NMD) pathway. The F11 gene consists of 15 exons spanning approximately 23 kb on chromosome 4q35 and codes for coagulation factor XI (FXI), a 160-kDa dimeric zymogen composed of 4 apple domains and a serine protease domain. Here, we characterized the F11 splicing pattern in human liver and platelets identifying multiple in-frame and out-of-frame splicing events. Inhibition of NMD resulted in the up-regulation of all unproductively spliced F11 transcripts, thus providing evidence that these PTC-containing mRNAs are under the control of NMD. Among in-frame alternatively spliced transcripts, the one skipping exons 6 and 7 would lead to the synthesis of a FXI protein lacking 1 apple domain (FXI-Δ6/7). Ex vivo expression in mammalian cells demonstrated that FXI-Δ6/7 is mostly retained intracellularly, and secreted only in low amounts. Traces of this FXI isoform were detectable in human plasma. Our results suggest that the coupling of alternative splicing and NMD may play a role in regulating F11 expression, and point to the existence of a novel FXI isoform.
Induction of tolerance to bone marrow allografts by donor-derived host nonreactive ex vivo–induced central memory CD8 T cells
Authors: Ophir Eran , Eidelstein Yaki , Afik Ran , Bachar-Lustig Esther , Reisner Yair
Published: December 2009

Enabling engraftment of allogeneic T cell–depleted bone marrow (TDBM) under reduced-intensity conditioning represents a major challenge in bone marrow transplantation (BMT). Anti–third-party cytotoxic T lymphocytes (CTLs) were previously shown to be endowed with marked ability to delete host antidonor T cells in vitro, but were found to be less effective in vivo. This could result from diminished lymph node (LN) homing caused by the prolonged activation, which induces a CD44+CD62L− effector phenotype, and thereby prevents effective colocalization with, and neutralization of, alloreactive host T cells (HTCs). In the present study, LN homing, determined by imaging, was enhanced upon culture conditions that favor the acquisition of CD44+CD62L+ central memory cell (Tcm) phenotype by anti–third-party CD8+ cells. These Tcm-like cells displayed strong proliferation and prolonged persistence in BM transplant recipients. Importantly, adoptively transferred HTCs bearing a transgenic T-cell receptor (TCR) with antidonor specificity were efficiently deleted only by donor-type Tcms. All these attributes were found to be associated with improved efficacy in overcoming T cell–mediated rejection of TDBM, thereby enabling high survival rate and long-term donor chimerism, without causing graft-versus-host disease. In conclusion, anti–third-party Tcms, which home to recipient LNs and effectively delete antidonor T cells, could provide an effective and novel tool for overcoming rejection of BM allografts.
Global lung health: the colliding epidemics of tuberculosis, tobacco smoking, HIV and COPD
Authors: van Zyl Smit R. N. , Pai M. , Yew W. W. , Leung C. C. , Zumla A. , Bateman E. D. , Dheda K.
Published: December 2009

Tuberculosis (TB), smoking, HIV and chronic obstructive pulmonary disease (COPD) are burgeoning epidemics in developing countries. The link between TB and HIV is well established. Less well recognised is the strong relationship between tobacco smoking and the development and natural history of TB. These associations are of considerable relevance to public health and disease outcomes in individuals with TB. Moreover, tobacco smoking, a modifiable risk factor, is associated with poorer outcomes in HIV-associated opportunistic infections, of which TB is the commonest in developing countries. It is now also becoming clear that TB, like tobacco smoke, besides its known consequences of bronchiectasis and other pulmonary morbidity, is also a significant risk factor for the development of COPD. Thus, there is a deleterious and synergistic interaction between TB, HIV, tobacco smoking and COPD in a large proportion of the world’s population. Further work, specifically mechanistic and epidemiological studies, is required to clarify the role of tobacco smoke on the progression of TB and HIV infection, and to assess the impact of smoking cessation interventions. These interactions deserve urgent attention and have major implications for coordinated public health planning and policy recommendations in the developing world.
Treatment of extensive-stage small cell lung carcinoma: current status and future prospects
Authors: Demedts I. K. , Vermaelen K. Y. , van Meerbeeck J. P.
Published: December 2009

Small cell lung cancer (SCLC) is an aggressive lung tumour strongly associated with cigarette smoking, with patients often presenting with metastatic disease at the time of diagnosis. Although SCLC is very chemoradiosensitive and high response rates are obtained with treatment, relapse rates are high and the prognosis remains very poor.

In limited-stage SCLC, the overall survival rate has been significantly improved by adding dose-hyperfractionated thoracic radiotherapy and prophylactic cranial irradiation to systemic chemotherapy. In contrast, little progress has been made in the treatment of extensive-stage SCLC (ES-SCLC), apart from the recently documented survival gain by the addition of prophylactic cranial irradiation.

First-line therapy in ES-SCLC currently consists of chemotherapy, combining a platinum drug with either etoposide or irinotecan as a possible alternative.

New treatments are needed in order to improve the prognosis of ES-SCLC, as median survival with current standard treatment is still only 9–10 months from diagnosis. The present review focuses on the management of ES-SCLC, with special attention to the development of new treatment options.
Conservation of intron and intein insertion sites: implications for life histories of parasitic genetic elements
Authors: Swithers Kristen S , Senejani Alireza G , Fournier Gregory P , Gogarten J Peter
Published: January 2010

Background

Inteins and introns are genetic elements that are removed from proteins and RNA after translation or transcription, respectively. Previous studies have suggested that these genetic elements are found in conserved parts of the host protein. To our knowledge this type of analysis has not been done for group II introns residing within a gene. Here we provide quantitative statistical support from an analyses of proteins that host inteins, group I introns, group II introns and spliceosomal introns across all three domains of life.

Results

To determine whether or not inteins, group I, group II, and spliceosomal introns are found preferentially in conserved regions of their respective host protein, conservation profiles were generated and intein and intron positions were mapped to the profiles. Fisher's combined probability test was used to determine the significance of the distribution of insertion sites across the conservation profile for each protein. For a subset of studied proteins, the conservation profile and insertion positions were mapped to protein structures to determine if the insertion sites correlate to regions of functional activity. All inteins and most group I introns were found to be preferentially located within conserved regions; in contrast, a bacterial intein-like protein, group II and spliceosomal introns did not show a preference for conserved sites.

Conclusions

These findings demonstrate that inteins and group I introns are found preferentially in conserved regions of their respective host proteins. Homing endonucleases are often located within inteins and group I introns and these may facilitate mobility to conserved regions. Insertion at these conserved positions decreases the chance of elimination, and slows deletion of the elements, since removal of the elements has to be precise as not to disrupt the function of the protein. Furthermore, functional constrains on the targeted site make it more difficult for hosts to evolve immunity to the homing endonuclease. Therefore, these elements will better survive and propagate as molecular parasites in conserved sites. In contrast, spliceosomal introns and group II introns do not show significant preference for conserved sites and appear to have adopted a different strategy to evade loss.
MicroRNA and tasiRNA diversity in mature pollen of Arabidopsis thaliana
Authors: Grant-Downton Robert , Le Trionnaire Gael , Schmid Ralf , Rodriguez-Enriquez Josefina , Hafidh Said , Mehdi Saher , Twell David , Dickinson Hugh
Published: December 2009

Background

New generation sequencing technology has allowed investigation of the small RNA populations of flowering plants at great depth. However, little is known about small RNAs in their reproductive cells, especially in post-meiotic cells of the gametophyte generation. Pollen - the male gametophyte - is the specialised haploid structure that generates and delivers the sperm cells to the female gametes at fertilisation. Whether development and differentiation of the male gametophyte depends on the action of microRNAs and trans-acting siRNAs guiding changes in gene expression is largely unknown. Here we have used 454 sequencing to survey the various small RNA populations present in mature pollen of Arabidopsis thaliana.

Results

In this study we detected the presence of 33 different microRNA families in mature pollen and validated the expression levels of 17 selected miRNAs by Q-RT-PCR. The majority of the selected miRNAs showed pollen-enriched expression compared with leaves. Furthermore, we report for the first time the presence of trans-acting siRNAs in pollen. In addition to describing new patterns of expression for known small RNAs in each of these classes, we identified 7 putative novel microRNAs. One of these, ath-MIR2939, targets a pollen-specific F-box transcript and we demonstrate cleavage of its target mRNA in mature pollen.

Conclusions

Despite the apparent simplicity of the male gametophyte, comprising just two different cell types, pollen not only utilises many miRNAs and trans-acting siRNAs expressed in the somatic tissues but also expresses novel miRNAs.
Proteomic analysis of honeybee worker (Apis mellifera) hypopharyngeal gland development
Authors: Feng Mao , Fang Yu , Li Jianke
Published: December 2009

Background

Hypopharyngeal glands (HG) of honeybee workers play an important role in honeybee nutrition and caste differentiation. Previous research mainly focused on age-dependent morphological, physiological, biochemical and genomic characters of the HG. Here proteomics and biochemical network analysis were used to follow protein changes during the HG development.

Results

A total of 87, 76, 85, 74, 71, and 55 proteins were unambiguously identified on day 1, 3, 6, 12, 15 and 20, respectively. These proteins were major royal jelly proteins (MRJPs), metabolism of carbohydrates, lipids and proteins, cytoskeleton, development regulation, antioxidant, molecule transporter, regulation of transcription/translation, proteins with folding functions. The most interesting is that MRJP's that have been detected in the HG of the newly emerged worker bees. The MRJP's expression is at peak level from 6-12 days, was validated by western blot analysis of MRJP1, 2 and 3. Moreover, 35 key node proteins were found in the biochemical networks of the HG.

Conclusions

HG secretes RJ at peak level within 6-12 days, but the worker bee can secrete royal jelly (RJ) since birth, which is a new finding. Several key node proteins play an important role in the biochemical networks of the developing HG. This provides us some target proteins when genetically manipulating honeybees.
Improving the efficiency of genomic loci capture using oligonucleotide arrays for high throughput resequencing
Authors: Lee Hane , O'Connor Brian D , Merriman Barry , Funari Vincent A , Homer Nils , Chen Zugen , Cohn Daniel H , Nelson Stanley F
Published: January 2010

Background

The emergence of next-generation sequencing technology presents tremendous opportunities to accelerate the discovery of rare variants or mutations that underlie human genetic disorders. Although the complete sequencing of the affected individuals' genomes would be the most powerful approach to finding such variants, the cost of such efforts make it impractical for routine use in disease gene research. In cases where candidate genes or loci can be defined by linkage, association, or phenotypic studies, the practical sequencing target can be made much smaller than the whole genome, and it becomes critical to have capture methods that can be used to purify the desired portion of the genome for shotgun short-read sequencing without biasing allelic representation or coverage. One major approach is array-based capture which relies on the ability to create a custom in-situ synthesized oligonucleotide microarray for use as a collection of hybridization capture probes. This approach is being used by our group and others routinely and we are continuing to improve its performance.

Results

Here, we provide a complete protocol optimized for large aggregate sequence intervals and demonstrate its utility with the capture of all predicted amino acid coding sequence from 3,038 human genes using 241,700 60-mer oligonucleotides. Further, we demonstrate two techniques by which the efficiency of the capture can be increased: by introducing a step to block cross hybridization mediated by common adapter sequences used in sequencing library construction, and by repeating the hybridization capture step. These improvements can boost the targeting efficiency to the point where over 85% of the mapped sequence reads fall within 100 bases of the targeted regions.

Conclusions

The complete protocol introduced in this paper enables researchers to perform practical capture experiments, and includes two novel methods for increasing the targeting efficiency. Coupled with the new massively parallel sequencing technologies, this provides a powerful approach to identifying disease-causing genetic variants that can be localized within the genome by traditional methods.
Multilocus variable-number tandem repeat analysis for molecular typing and phylogenetic analysis of Shigella flexneri
Authors: Wang You-Wun , Watanabe Haruo , Phung Dac Cam , Tung Sheng Kai , Lee Yeong-Sheng , Terajima Jun , Liang Shiu-Yun , Chiou Chien-Shun
Published: December 2009

Background

Shigella flexneri is one of the causative agents of shigellosis, a major cause of childhood mortality in developing countries. Multilocus variable-number tandem repeat (VNTR) analysis (MLVA) is a prominent subtyping method to resolve closely related bacterial isolates for investigation of disease outbreaks and provide information for establishing phylogenetic patterns among isolates. The present study aimed to develop an MLVA method for S. flexneri and the VNTR loci identified were tested on 242 S. flexneri isolates to evaluate their variability in various serotypes. The isolates were also analyzed by pulsed-field gel electrophoresis (PFGE) to compare the discriminatory power and to evaluate the usefulness of MLVA as a tool for phylogenetic analysis of S. flexneri.

Results

Thirty-six VNTR loci were identified by exploring the repeat sequence loci in genomic sequences of Shigella species and by testing the loci on nine isolates of different subserotypes. The VNTR loci in different serotype groups differed greatly in their variability. The discriminatory power of an MLVA assay based on four most variable VNTR loci was higher, though not significantly, than PFGE for the total isolates, a panel of 2a isolates, which were relatively diverse, and a panel of 4a/Y isolates, which were closely-related. Phylogenetic groupings based on PFGE patterns and MLVA profiles were considerably concordant. The genetic relationships among the isolates were correlated with serotypes. The phylogenetic trees constructed using PFGE patterns and MLVA profiles presented two distinct clusters for the isolates of serotype 3 and one distinct cluster for each of the serotype groups, 1a/1b/NT, 2a/2b/X/NT, 4a/Y, and 6. Isolates that had different serotypes but had closer genetic relatedness than those with the same serotype were observed between serotype Y and subserotype 4a, serotype X and subserotype 2b, subserotype 1a and 1b, and subserotype 3a and 3b.

Conclusions

The 36 VNTR loci identified exhibited considerably different degrees of variability among S. flexneri serotype groups. VNTR locus could be highly variable in a serotype but invariable in others. MLVA assay based on four highly variable loci could display a comparable resolving power to PFGE in discriminating isolates. MLVA is also a prominent molecular tool for phylogenetic analysis of S. flexneri; the resulting data are beneficial to establish clear clonal patterns among different serotype groups and to discern clonal groups among isolates within the same serotype. As highly variable VNTR loci could be serotype-specific, a common MLVA protocol that consists of only a small set of loci, for example four to eight loci, and that provides high resolving power to all S. flexneri serotypes may not be obtainable.
Differentially expressed alternatively spliced genes in Malignant Pleural Mesothelioma identified using massively parallel transcriptome sequencing
Authors: Dong Lingsheng , Jensen Roderick V , De Rienzo Assunta , Gordon Gavin J , Xu Yanlong , Sugarbaker David J , Bueno Raphael
Published: December 2009

Background

Analyses of Expressed Sequence Tags (ESTs) databases suggest that most human genes have multiple alternative splice variants. The alternative splicing of pre-mRNA is tightly regulated during development and in different tissue types. Changes in splicing patterns have been described in disease states. Recently, we used whole-transcriptome shotgun pryrosequencing to characterize 4 malignant pleural mesothelioma (MPM) tumors, 1 lung adenocarcinoma and 1 normal lung. We hypothesized that alternative splicing profiles might be detected in the sequencing data for the expressed genes in these samples.

Methods

We developed a software pipeline to map the transcriptome read sequences of the 4 MPM samples and 1 normal lung sample onto known exon junction sequences in the comprehensive AceView database of expressed sequences and to count how many reads map to each junction. 13,274,187 transcriptome reads generated by the Roche/454 sequencing platform for 5 samples were compared with 151,486 exon junctions from the AceView database. The exon junction expression index (EJEI) was calculated for each exon junction in each sample to measure the differential expression of alternative splicing events. Top ten exon junctions with the largest EJEI difference between the 4 mesothelioma and the normal lung sample were then examined for differential expression using Quantitative Real Time PCR (qRT-PCR) in the 5 sequenced samples. Two of the differentially expressed exon junctions (ACTG2.aAug05 and CDK4.aAug05) were further examined with qRT-PCR in additional 18 MPM and 18 normal lung specimens.

Results

We found 70,953 exon junctions covered by at least one sequence read in at least one of the 5 samples. All 10 identified most differentially expressed exon junctions were validated as present by RT-PCR, and 8 were differentially expressed exactly as predicted by the sequence analysis. The differential expression of the AceView exon junctions for the ACTG2 and CDK4 genes were also observed to be statistically significant in an additional 18 MPM and 18 normal lung samples examined using qRT-PCR. The differential expression of these two junctions was shown to successfully classify these mesothelioma and normal lung specimens with high sensitivity (89% and 78%, respectively).

Conclusion

Whole-transcriptome shotgun sequencing, combined with a downstream bioinformatics pipeline, provides powerful tools for the identification of differentially expressed exon junctions resulting from alternative splice variants. The alternatively spliced genes discovered in the study could serve as useful diagnostic markers as well as potential therapeutic targets for MPM.