bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why do parents enrol their children in research: a narrative synthesis
Authors: Fisher Helen R , McKevitt Christopher , Boaz Annette 
Published: April 2011

ObjectiveRecent legislation mandating the inclusion of children in clinical trials has resulted in an increase in the number of children participating in research. We reviewed the literature regarding the reasons parents chose to accept or decline an invitation to enrol their children in clinical research.MethodsWe searched for qualitative studies, written in the English language that considered the experiences of parents who had been invited to enrol their children in research. SCOPUS and Web of Knowledge electronic databases and reference lists of retrieved articles and review papers were searched. Retrieved articles were synthesised using the narrative synthesis method.Results16 qualitative studies exploring the experiences of parents living in five countries whose children had a range of health conditions of varying severity were included. The health status of the child appeared to influence parents' reasons for participation. Parents whose children had life threatening conditions often considered they had no choice but to participate and many welcomed the innovation offered through research participation. Such parents also viewed the risks of research less negatively than those whose children were healthy or in the stable stage of a chronic condition. This raises questions regarding the voluntariness of informed consent by such parents.ConclusionsA tailored approach is needed when discussing research participation with parents of eligible children. While parents of healthy children may be more open to discussions of altruism, those whose children have life threatening illnesses should be given adequate information about the alternatives to, and risks of, research participation.
Achieving online consent to participation in large-scale gene-environment studies: a tangible destination
Authors: Wood Fiona , Kowalczuk Jenny , Elwyn Glyn , Mitchell Clive , Gallacher John 
Published: April 2011

BackgroundPopulation based genetics studies are dependent on large numbers of individuals in the pursuit of small effect sizes. Recruiting and consenting a large number of participants is both costly and time consuming. We explored whether an online consent process for large-scale genetics studies is acceptable for prospective participants using an example online genetics study.MethodsWe conducted semi-structured interviews with 42 members of the public stratified by age group, gender and newspaper readership (a measure of social status). Respondents were asked to use a website designed to recruit for a large-scale genetic study. After using the website a semi-structured interview was conducted to explore opinions and any issues they would have. Responses were analysed using thematic content analysis.ResultsThe majority of respondents said they would take part in the research (32/42). Those who said they would decline to participate saw fewer benefits from the research, wanted more information and expressed a greater number of concerns about the study. Younger respondents had concerns over time commitment. Middle aged respondents were concerned about privacy and security. Older respondents were more altruistic in their motivation to participate. Common themes included trust in the authenticity of the website, security of personal data, curiosity about their own genetic profile, operational concerns and a desire for more information about the research.ConclusionsOnline consent to large-scale genetic studies is likely to be acceptable to the public. The online consent process must establish trust quickly and effectively by asserting authenticity and credentials, and provide access to a range of information to suit different information preferences.
An empirical study on the preferred size of the participant information sheet in research
Authors: Antoniou Evangelia E , Draper Heather , Reed Keith , Burls Amanda , Southwood Taunton R , Zeegers Maurice P 
Published: April 2011

BackgroundInformed consent is a requirement for all research. It is not, however, clear how much information is sufficient to make an informed decision about participation in research. Information on an online questionnaire about childhood development was provided through an unfolding electronic participant sheet in three levels of information.Methods552 participants, who completed the web-based survey, accessed and spent time reading the participant information sheet (PIS) between July 2008 and November 2009. The information behaviour of the participants was investigated. The first level contained less information than might be found on a standard PIS, the second level corresponded to a standard PIS, and the third contained more information than on a standard PIS. The actual time spent on reading the information provided in three incremental levels and the participants' evaluation of the information were calculated.Results77% of the participants chose to access the first level of information, whereas 12% accessed the first two levels, 6% accessed all three levels of information and 23% participated without accessing information. The most accessed levels of information were those that corresponded to the average reading times.ConclusionThe brief information provided in the first level was sufficient for participants to make informed decisions, while a sizeable minority of the participants chose not to access any information at all. This study adds to the debate about how much information is required to make a decision about participation in research and the results may help inform the future development of information sheets by providing data on participants' actual needs when deciding about questionnaire surveys.
The ‘patient's physician one-step removed’: the evolving roles of medical tourism facilitators: Table 1
Authors: Snyder Jeremy , Crooks Valorie A , Adams Krystyna , Kingsbury Paul , Johnston Rory 
Published: April 2011

BackgroundMedical tourism involves patients travelling internationally to receive medical services. This practice raises a range of ethical issues, including potential harms to the patient's home and destination country and risks to the patient's own health. Medical tourists often engage the services of a facilitator who may book travel and accommodation and link the patient with a hospital abroad. Facilitators have the potential to exacerbate or mitigate the ethical concerns associated with medical tourism, but their roles are poorly understood.Methods12 facilitators were interviewed from 10 Canadian medical tourism companies.ResultsThree themes were identified: facilitators' roles towards the patient, health system and medical tourism industry. Facilitators' roles towards the patient were typically described in terms of advocacy and the provision of information, but limited by facilitators' legal liability. Facilitators felt they played a positive role in the lives of their patients and the Canadian health system and served as catalysts for reform, although they noted an adversarial relationship with some Canadian physicians. Many facilitators described personally visiting medical tourism sites and forming personal relationships with surgeons abroad, but noted the need for greater regulation of their industry.ConclusionFacilitators play a substantial and evolving role in the practice of medical tourism and may be entering a period of professionalisation. Because of the key role of facilitators in determining the effects of medical tourism on patients and public health, this paper recommends a planned conversation between medical tourism stakeholders to define and shape facilitators' roles.
Deadly in pink: the impact of cigarette packaging among young women
Authors: Doxey Juliana , Hammond David 
Published: April 2011

BackgroundThis study sought to examine the impact of cigarette packaging on young women, including the impact of ‘plain’ packaging.MethodsParticipants were randomised to view eight cigarette packs designed according to one of four experimental conditions: fully-branded female brands; the same brands without descriptors (eg, ‘slims’); the same brands without brand imagery or descriptors (ie, ‘plain’ packs); and fully branded non-female brands as a control condition. Participants rated packs on perceived appeal, taste, tar, health risks and smoker ‘traits’.ResultsFully-branded female packs were rated as significantly more appealing than ‘no descriptor’ packs, ‘plain’ packs and non-female branded packs. Female branded packs were associated with a greater number of positive attributes including glamour, slimness and attractiveness, compared to brands without descriptors and ‘plain’ packs. Women who viewed plain packs were less likely to believe that smoking helps people control their appetite—an important predictor of smoking among young women—compared to women who viewed branded female packs.Conclusions‘Plain’ packaging—removing colours and design elements—and removing descriptors such as ‘slims’ from packs may reduce brand appeal and thereby susceptibility to smoking among young women.
Role of substrate on the dendroclimatic response of Scots pine from varying elevations in northern Scotland
Authors: Moir A.K. , Leroy S.A.G. , Helama S. 
Published: April 2011

The influence of substrate was evaluated by comparing annual ring widths of Scots pine (Pinus sylvestris L.) with climate data at 13 new sites (five bog, three peat, and five soil), together with 17 previously studied soil sites in northern Scotland. Radial growth rates <1.0 and >1.5 mm·year–1 differentiate well between pine growing on bog and peat, respectively, highlighting the role of pine as a indicator of water levels in these environments. Scots pine chronologies from bog are shown to have a weak temperature–growth response and so limit potential in dendroclimatic reconstructions. However, correlation analysis shows temperature in January–February and July–August to be important determinants of the radial growth of Scots pine on soil. Moving correlation analysis indicates that the relationship between the radial growth of pine on soil near the altitudinal tree line and summer temperature (July–August) is time stable, despite an increase of temperature in northern Scotland. However, winter (January–February) temperature has become less limiting since the 1920s. Scots pine at some soil, bog, and peat sites have increased or developed correlation with October temperature since the 1940s, suggesting an extension of the growth season, particularly on the western coast of Scotland.
Impact of primary and secondary machinery tracks on fine root growth of sugar maple after selection cutting
Authors: Malo Catherine , Messier Christian 
Published: April 2011

Selection cutting, where approximately 30% of the trees are removed every 30 years, is the main silvicultural treatment used in temperate deciduous forests of Quebec (Canada). Concerns have been raised that the use of heavy machinery is creating soil disturbances that are negatively affecting the growth and survival of remaining trees. The aim of the study was to determine if heavy machinery is affecting the growth, morphology, and architecture of sugar maple (Acer saccharum Marsh.) fine roots in and around machinery tracks left after selection logging. The study site, a sugar maple dominated stand, was located in southern Quebec. Root ingrowth bags and standard root cores were used to compare fine root growth, morphology, and architecture in and around machinery tracks one year after logging. Fine root growth of maple was reduced fivefold in both primary (multiple trip) and secondary (only one trip) machinery tracks compared with the control. There was a nonstatistical reduction in fine root growth within 1 m of the tracks. Because machinery tracks cover between 15% and 25% of a stand after selection logging, such reduction in fine root growth could be significant for the growth and survival of the remaining mature maple trees.
Allometric equations for young northern hardwoods: the importance of age-specific equations for estimating aboveground biomass
Authors: Fatemi Farrah R. , Yanai Ruth D. , Hamburg Steven P. , Vadeboncoeur Matthew A. , Arthur Mary A. , Briggs Russell D. , Levine Carrie R. 
Published: April 2011

Estimates of aboveground biomass and nutrient stocks are commonly derived using equations that describe tree dimensional relationships. Despite the widespread use of this approach, there is little information about whether equations specific to stand age are necessary for accurate biomass predictions. We developed equations for small trees (2–12 cm diameter) of six species in four young northern hardwood stands. We then compared our equations with equations used frequently in the literature that were developed in mature stands (Whittaker et al. 1974. Ecol. Monogr. 44: 233–252). Our equations for yellow birch ( Betula alleghaniensis Britt.) predicted 11%–120% greater stem wood for individual trees compared with the equations from Whittaker et al. and, on average, 50% greater aboveground yellow birch biomass in the four stands that we studied. Differences were less pronounced for sugar maple ( Acer saccharum Marsh.) and American beech ( Fagus grandifolia Ehrh.); our equations predicted, on average, 9% greater aboveground stand biomass for sugar maple and 3% lower biomass for American beech compared with Whittaker et al. Our results suggest that stand age may be an important factor influencing the aboveground allometry and biomass of small yellow birch trees in these developing northern hardwood stands.
Litter layers (Oie) as a calcium source of sugar maple seedlings in a northern hardwood forest
Authors: Fahey Timothy J. , Blum Joel D. 
Published: April 2011

The role of the Oie horizon in calcium supply of sugar maple (Acer saccharum Marsh.) seedlings was evaluated. Forest floor Oie horizon was reciprocally transplanted on 1 m2 quadrats between a Ca-treated (W1) and a reference (W3) watershed, and sugar maple seeds were planted on the quadrats. The Oie horizon in W1 exhibited a greatly increased Ca:Sr molar ratio compared with the reference W3 (550 vs. 220), allowing distinction of this Ca source in seedling tissues. Foliage and fine roots of maple seedlings growing on quadrats in W3 with Oie transplanted from W1 exhibited Ca:Sr ratios intermediate between the Oie and underlying native soil horizons, demonstrating the role of Oie in seedling Ca nutrition. However, apparently strong and temporally changing discrimination of Ca and Sr in seedling uptake and internal transport confounded quantitative evaluation.
Exosomes Released by Melanoma Cells Prepare Sentinel Lymph Nodes for Tumor Metastasis
Authors: Hood Joshua L. , San Roman Susana , Wickline Samuel A. 
Published: April 2011

Abstract
Exosomes are naturally occurring biological nanovesicles utilized by tumors to communicate signals to local and remote cells and tissues. Melanoma exosomes can incite a proangiogenic signaling program capable of remodeling tissue matrices. In this study, we show exosome-mediated conditioning of lymph nodes and define microanatomic responses that license metastasis of melanoma cells. Homing of melanoma exosomes to sentinel lymph nodes imposes synchronized molecular signals that effect melanoma cell recruitment, extracellular matrix deposition, and vascular proliferation in the lymph nodes. Our findings highlight the pathophysiologic role and mechanisms of an exosome-mediated process of microanatomic niche preparation that facilitates lymphatic metastasis by cancer cells. Cancer Res; 71(11); 3792–801. ©2011 AACR.
PIK3R1 (p85α) Is Somatically Mutated at High Frequency in Primary Endometrial Cancer
Authors: Urick Mary E. , Rudd Meghan L. , Godwin Andrew K. , Sgroi Dennis , Merino Maria , Bell Daphne W. 
Published: April 2011

Abstract
Phosphoinositide 3-kinase (PI3K) is an important therapeutic target. Mutations in PIK3CA, which encodes p110α, the catalytic subunit of PI3K, occur in endometrioid endometrial cancers (EEC) and nonendometrioid endometrial cancers (NEEC). The goal of this study was to determine whether PIK3R1, which encodes p85α, the inhibitory subunit of PI3K, is mutated in endometrial carcinoma. We carried out exonic sequencing of PIK3R1 from 42 EECs and 66 NEECs. The pattern of PIK3R1 mutations was compared with the patterns of PIK3CA, PTEN, and KRAS mutations. The biochemical effect of seven PIK3R1 mutations was examined by stable expression in U2OS cells, followed by coimmunoprecipitation analysis of p110α, and Western blotting of phospho-AKTSer473 (p-AKTSer473). We found that PIK3R1 was somatically mutated in 43% of EECs and 12% of NEECs. The majority of mutations (93.3%) were localized to the p85α-nSH2 and -iSH2 domains. Several mutations were recurrent. PIK3R1 mutations were significantly (P = 0.0015) more frequent in PIK3CA-wild type EECs (70%) than in PIK3CA mutant EECs (18%). Introduction of wild-type p85α into U2OS cells reduced the level of p-AKTSer473 compared with the vector control. Five p85α mutants, p85αdelH450-E451, p85αdelK459, p85αdelY463-L466, p85αdelR574-T576, and the p85αN564D positive control, were shown to bind p110α and led to increased levels of p-AKTSer473. The p85αR348X and p85αK511VfsX2 mutants did not bind p110α and showed no appreciable change in p-AKTSer473 levels. In conclusion, our study has revealed a new mode of PI3K alteration in primary endometrial tumors and warrants future studies to determine whether PIK3R1 mutations correlate with clinical outcome to targeted therapies directed against the PI3K pathway in EEC and NEEC. Cancer Res; 71(12); 4061–7. ©2011 AACR.
Effector T-Cell Infiltration Positively Impacts Survival of Glioblastoma Patients and Is Impaired by Tumor-Derived TGF-β
Authors: Lohr Jennifer , Ratliff Thomas , Huppertz Andrea , Ge Yingzi , Dictus Christine , Ahmadi Rezvan , Grau Stefan , Hiraoka Nobuyoshi , Eckstein Volker , Ecker Rupert C. , Korff Thomas , von Deimling Andreas , Unterberg Andreas , Beckhove Philipp , Herold-Mende Christel 
Published: April 2011

Abstract
Purpose: In glioma—in contrast to various other cancers—the impact of T-lymphocytes on clinical outcome is not clear. We investigated the clinical relevance and regulation of T-cell infiltration in glioma.
Experimental Design: T-cell subpopulations from entire sections of 93 WHO°II–IV gliomas were computationally identified using markers CD3, CD8, and Foxp3; survival analysis was then done on primary glioblastomas (pGBM). Endothelial cells expressing cellular adhesion molecules (CAM) were similarly computationally quantified from the same glioma tissues. Influence of prominent cytokines (as measured by ELISA from 53 WHO°II–IV glioma lysates) on CAM-expression in GBM-isolated endothelial cells was determined using flow cytometry. The functional relevance of the cytokine-mediated CAM regulation was tested in a transmigration assay using GBM-derived endothelial cells and autologous T-cells.
Results: Infiltration of all T-cell subsets increased in high-grade tumors. Most strikingly, within pGBM, elevated numbers of intratumoral effector T cells (Teff, cytotoxic and helper) significantly correlated with a better survival; regulatory T cells were infrequently present and not associated with GBM patient outcome. Interestingly, increased infiltration of Teff cells was related to the expression of ICAM-1 on the vessel surface. Transmigration of autologous T cells in vitro was markedly reduced in the presence of CAM-blocking antibodies. We found that TGF-β molecules impeded transmigration and downregulated CAM-expression on GBM-isolated endothelial cells; blocking TGF-β receptor signaling increased transmigration.
Conclusions: This study provides comprehensive and novel insights into occurrence and regulation of T-cell infiltration in glioma. Specifically, targeting TGF-β1 and TGF-β2 might improve intratumoral T-cell infiltration and thus enhance effectiveness of immunotherapeutic approaches. Clin Cancer Res; 17(13); 4296–308. ©2011 AACR.
The Viral Load of Epstein–Barr Virus (EBV) DNA in Peripheral Blood Predicts for Biological and Clinical Characteristics in Hodgkin Lymphoma
Authors: Hohaus Stefan , Santangelo Rosaria , Giachelia Manuela , Vannata Barbara , Massini Giuseppina , Cuccaro Annarosa , Martini Maurizio , Cesarini Valeriana , Cenci Tonia , D'Alo Francesco , Voso Maria Teresa , Fadda Giovanni , Leone Giuseppe , Larocca Luigi M 
Published: April 2011

Abstract
Purpose: The Epstein–Barr virus (EBV) is present in the malignant Hodgkin/Reed–Sternberg (HRS) cells of 20% to 40% cases of Hodgkin lymphoma (HL) in Western countries. We were interested in the detection and quantification of cell-free plasma EBV-DNA as an indicator of biological and clinical characteristics in EBV-associated HL.
Experimental Design: EBV was detected in peripheral blood compartments (whole blood, plasma, and mononuclear cells) at diagnosis by real-time PCR for the EBNA (EB nuclear antigen) region (n = 93) and in HRS cells by in situ hybridization for EBV-encoded small RNAs (EBER; n = 63). These data were correlated to histological and clinical characteristics, EBV serology, circulating cell-free DNA, and interleukin (IL)-6 levels.
Results: Detection of EBV-DNA in plasma had a high specificity (90%), but a relatively low sensitivity (65%) to predict for EBV association. The viral load was higher in patients with advanced stage disease, older age in the presence of B-symptoms, and international prognostic score more than 2. The presence of EBV in HRS cells and higher plasma EBV-DNA copy numbers correlated to an increased frequency of tumor-infiltrating CD68+ macrophages in lymph node biopsies. Plasma EBV-DNA load correlated to circulating cell-free DNA and IL-6 levels, and inversely correlated to lymphocyte counts and EBNA1 antibody titers.
Conclusion: Although the presence of EBV-DNA in peripheral blood cannot be regarded as a surrogate marker for EBER, the plasma EBV-DNA load at HL diagnosis is an indicator of disease activity and biological characteristics associated with negative prognosis. Moreover, the inverse correlation to EBNA1 antibody titers and lymphocyte counts may indicate a reduction in immunosurveillance, favoring the expansion of EBV-HRS cells in HL. Clin Cancer Res; 17(9); 2885–92. ©2011 AACR.
CYLD Inhibits Tumorigenesis and Metastasis by Blocking JNK/AP1 Signaling at Multiple Levels
Authors: de Marval Paula Miliani , Lutfeali Shazia , Jin Jane Y. , Leshin Benjamin , Selim M. Angelica , Zhang Jennifer Y. 
Published: April 2011

Abstract
CYLD has been recognized as a tumor suppressor due to its dominant genetic linkage to multiple types of epidermal tumors and a range of other cancers. The molecular mechanisms governing CYLD control of skin cancer are still unclear. Here, we showed that K14-driven epidermal expression of a patient-relevant and catalytically deficient CYLD truncated mutant (CYLDm) sensitized mice to skin tumor development in response to 7,12-dimethylbenz[α]anthracene (DMBA)/(12-O-tetradecanoylphorbol-13-acetate) TPA challenge. Tumors developed on transgenic mice were prone to malignant progression and lymph node metastasis and displayed increased activation of c-Jun-NH2-kinase (JNK) and the downstream c-Jun and c-Fos proteins. Most importantly, topical application of a pharmacologic JNK inhibitor significantly reduced tumor development and abolished metastasis in the transgenic mice. Further in line with these animal data, exogenous expression of CYLDm in A431, a human squamous cell carcinoma (SCC) cell line, markedly enhanced cell growth, migration, and subcutaneous tumor growth in an AP1-depdendent manner. In contrast, expression of the wild-type CYLD inhibited SCC tumorigenesis and AP1 function. Most importantly, CYLDm not only increased JNK activation but also induced an upregulation of K63 ubiquitination on both c-Jun and c-Fos, leading to sustained AP1 activation. Our findings uncovered c-Jun and c-Fos as novel CYLD targets and underscore that CYLD controls epidermal tumorigenesis through blocking the JNK/AP1 signaling pathway at multiple levels. Cancer Prev Res; 4(6); 851–9. ©2011 AACR.