bluuebunny/crossref_metadata_2025_split huggingface dataset:
North American Triple Reassortant and Eurasian H1N1 Swine Influenza Viruses Do Not Readily Reassort to Generate a 2009 Pandemic H1N1-Like Virus
Authors: Ma Wenjun , Liu Qinfang , Qiao Chuanling , del Real Gustavo , García-Sastre Adolfo , Webby Richard J. , Richt Jürgen A. 
Published: March 2014

ABSTRACT
The 2009 pandemic H1N1 virus (pH1N1) was derived through reassortment of North American triple reassortant and Eurasian avian-like swine influenza viruses (SIVs). To date, when, how and where the pH1N1 arose is not understood. To investigate viral reassortment, we coinfected cell cultures and a group of pigs with or without preexisting immunity with a Eurasian H1N1 virus, A/Swine/Spain/53207/2004 (SP04), and a North American triple reassortant H1N1 virus, A/Swine/Kansas/77778/2007 (KS07). The infected pigs were cohoused with one or two groups of contact animals to investigate viral transmission. In coinfected MDCK or PK15 continuous cell lines with KS07 and SP04 viruses, more than 20 different reassortant viruses were found. In pigs without or with preexisting immunity (immunized with commercial inactivated swine influenza vaccines) and coinfected with both viruses, six or seven reassortant viruses, as well as the parental viruses, were identified in bronchoalveolar lavage fluid samples from the lungs. Interestingly, only one or two viruses transmitted to and were detected in contact animals. No reassortant containing a gene constellation similar to that of pH1N1 virus was found in either coinfected cells or pigs, indicating that the reassortment event that resulted in the generation of this virus is a rare event that likely involved specific viral strains and/or a favorable, not-yet-understood environment.

IMPORTANCE
The 2009 pandemic-like H1N1 virus could not be reproduced either in cell cultures or in pigs coinfected with North American triple reassortant H1N1 and Eurasian H1N1 swine influenza viruses. This finding suggests that the generation of the 2009 pandemic H1N1 virus by reassortment was a rare event that likely involved specific viral strains and unknown factors. Different reassortant viruses were detected in coinfected pigs with and without preexisting immunity, indicating that host immunity plays a relevant role in driving viral reassortment of influenza A virus.
Pervasive Transcription of a Herpesvirus Genome Generates Functionally Important RNAs
Authors: Canny Susan P. , Reese Tiffany A. , Johnson L. Steven , Zhang Xin , Kambal Amal , Duan Erning , Liu Catherine Y. , Virgin Herbert W. 
Published: March 2014

ABSTRACT
Pervasive transcription is observed in a wide range of organisms, including humans, mice, and viruses, but the functional significance of the resulting transcripts remains uncertain. Current genetic approaches are often limited by their emphasis on protein-coding open reading frames (ORFs). We previously identified extensive pervasive transcription from the murine gammaherpesvirus 68 (MHV68) genome outside known ORFs and antisense to known genes (termed expressed genomic regions [EGRs]). Similar antisense transcripts have been identified in many other herpesviruses, including Kaposi’s sarcoma-associated herpesvirus and human and murine cytomegalovirus. Despite their prevalence, whether these RNAs have any functional importance in the viral life cycle is unknown, and one interpretation is that these are merely “noise” generated by functionally unimportant transcriptional events. To determine whether pervasive transcription of a herpesvirus genome generates RNA molecules that are functionally important, we used a strand-specific functional approach to target transcripts from thirteen EGRs in MHV68. We found that targeting transcripts from six EGRs reduced viral protein expression, proving that pervasive transcription can generate functionally important RNAs. We characterized transcripts emanating from EGRs 26 and 27 in detail using several methods, including RNA sequencing, and identified several novel polyadenylated transcripts that were enriched in the nuclei of infected cells. These data provide the first evidence of the functional importance of regions of pervasive transcription emanating from MHV68 EGRs. Therefore, studies utilizing mutation of a herpesvirus genome must account for possible effects on RNAs generated by pervasive transcription.

IMPORTANCE
The fact that pervasive transcription produces functionally important RNAs has profound implications for design and interpretation of genetic studies in herpesviruses, since such studies often involve mutating both strands of the genome. This is a common potential problem; for example, a conservative estimate is that there are an additional 73,000 nucleotides transcribed antisense to annotated ORFs from the 119,450-bp MHV68 genome. Recognizing the importance of considering the function of each strand of the viral genome independently, we used strand-specific approaches to identify six regions of the genome encoding transcripts that promoted viral protein expression. For two of these regions, we mapped novel transcripts and determined that targeting transcripts from these regions reduced viral replication and the expression of other viral genes. This is the first description of a function for these RNAs and suggests that novel transcripts emanating from regions of pervasive transcription are critical for the viral life cycle.
Implementation of a quality improvement programme to support advance care planning in five hospitals across a health region
Authors: Schofield G , Kreeger L , Meyer M , Swann D , Wijeratne A , Wood J , Stone P 
Published: March 2014

ObjectivesAdvance care planning (ACP) can help patients with a terminal illness to prepare for the end of their lives. This report describes a regional service improvement initiative to increase the identification of hospital inpatients at this stage in their illnesses and to increase the number of such patients who are offered the opportunity to start the process of ACP.MethodsData were collected prospectively over a 7 month period from four acute hospital trusts and a specialist cancer centre in the South-West London region. Each unit identified a specific patient population who were screened for eligibility to engage in the process of ACP. Data concerning the reasons for eligibility, the suitability for discussion and the various reasons why patients did not complete the process, were recorded.ResultsOver a 7 month period 1980 patients were screened and 559 (28.2%) were found to be potentially eligible for an ACP discussion. Of these 227/559 (40.6%) were deemed suitable for a discussion by medical staff. The majority of these patients (195/227; 86%) were offered the opportunity to undergo ACP discussions and 144/195 (73.8%) agreed to begin the process of ACP.ConclusionsThis report shows that a targeted approach can result in increased uptake in the number of patients who engage in ACP. However, systematic identification of potentially eligible patients requires a significant investment of clinical time and resources.
The use of healthcare resources in the last 3 years of life in patients with COPD and lung cancer in Denmark. A retrospective nationwide study
Authors: Husted Marie Gade , Kriegbaum Margit , Kirkegaard Nicolai , Lange Peter 
Published: March 2014

ObjectiveThe aim was to describe the use of healthcare resources during the last 3 years of life in patients who died from chronic obstructive pulmonary disease (COPD) or lung cancer (LC), including patients with LC and COPD.MethodsUsing data from Danish health registers, we identified 6648 individuals who, in 2010, died from COPD (n=3013) and LC (n=3635), including 775 from LC and COPD.ResultsPatients with COPD and LC had a high use of services in the last 3 years of life, but the trajectory for COPD was different from that of LC. Fifty-five per cent of subjects with LC received a reimbursement for the terminally ill compared to only 4% of subjects with COPD (p<0.0001). There was a significant increase in the number of individuals with COPD who received non-invasive ventilation (NIV) for the first time in the last 6 months of life. Individuals with COPD and LC had the highest consumption of health resources.ConclusionsThe high use of health resources together with the underuse of economic reimbursement in patients with terminal COPD suggest that more focus should be given to these patients. The need for NIV might be an indicator of poor prognosis and reflect an intensified need for palliative care. The high use of healthcare resources in patients with COPDandLC might indicate a substantial need for palliative care in these patients.
Income-related inequality in health and health-related behaviour: exploring the equalisation hypothesis
Authors: Vallejo-Torres Laura , Hale Daniel , Morris Stephen , Viner Russell M 
Published: March 2014

BackgroundPrevious studies have found the socioeconomic gradient in health among adolescents to be lower than that observed during childhood and adulthood. The aim of this study was to examine income-related inequalities in health and health-related behaviour across the lifespan in England to explore ‘equalisation’ in adolescence.MethodsWe used five years of data (2006–2010) from the Health Survey for England to explore inequalities in six indicators: self-assessed general health, longstanding illness, limiting longstanding illness, psychosocial wellbeing, obesity and smoking status. We ran separate analyses by age/gender groups. Inequality was measured using concentration indices.ResultsOur findings for longstanding illnesses, psychosocial wellbeing and obesity were consistent with the equalisation hypothesis. For these indicators, the extent of income-related inequality was lower among late adolescents (16–19 years) and young adults (20–24 years) compared to children and young adolescents (under 15 years), mid- and late-adults (25–44 and 45–64 years) and the elderly (65+ years). The remaining indicators showed lower inequality among adolescents compared to adults, but higher inequality when compared with children.ConclusionsOur work shows that inequalities occur across the life-course but that for some health issues there may be a period of equalisation in late adolescence and early adulthood.
Validation of a population coronary disease predictive system: the CASSANDRA model
Authors: Grau Maria , Subirana Isaac , Vila Joan , Elosua Roberto , Ramos Rafel , Sala Joan , Dégano Irene R , Tresserras Ricard , Bielsa Oscar , Marrugat Jaume 
Published: March 2014

BackgroundThe use of validated multivariate cardiovascular predictive models in a population setting is of interest for public health policy makers. We aimed to validate the estimations of the CASSANDRA model (coronary heart disease (CHD) incidence and CHD risk distribution), considering the population changes in age, sex and CHD risk factors prevalence in a 10-year period.MethodsWe compared the projected CHD incidence estimated with CASSANDRA with that observed in the Girona Heart Registry (REGICOR) for 1995–2004 and 2000–2009 in the population of Girona (Spain) aged 35–74 years. We used official age and sex distributions for this population. Baseline cardiovascular risk factors prevalence and the distribution of cardiovascular risk were obtained from three cross-sectional studies performed in 1995, 2000 and 2005. To validate the future distribution of cardiovascular risk, we tested the yearly CHD risk variance over the study period.ResultsNo significant differences between the estimated and observed annual CHD incidence per 100 000 men were found in 1995–2004 (CASSANDRA=457.8 and REGICOR=420.3, incidence rate ratio (IRR) (95% CI)=0.92 (0.89 to 0.96)) and in 2000–2009 (441.4 and 409.6, respectively, IRR=0.93 (0.90 to 0.96)). However, overpredictions of 18% and 22%, respectively, were observed in women (198.8 and 160.4, IRR=0.82 (0.77 to 0.86), and 197.1 and 152.8, IRR=0.78 (0.74 to 0.83), respectively). No significant differences were found in the CHD risk variance in the three different cross-sectional studies.ConclusionsThe CASSANDRA model produces valid estimates, particularly in men, of the future burden of disease and in the distribution of cardiovascular risk in individuals aged 35–74 years.
Extended two-phase flow model with mechanical capability to simulate gas migration in bentonite
Authors: Tawara Y. , Hazart A. , Mori K. , Tada K. , Shimura T. , Sato S. , Yamamoto S. , Asano H. , Namiki K. 
Published: March 2014

Abstract
Long-term gas migration through clays cannot be simulated by conventional two-phase flow models alone owing to the presence of material deformation. In this article, an extended two-phase flow model that incorporates mechanical effects is proposed. The model allows the formation of preferential pathway and considers the relation between pore moisture and pore deformation. It was carried out with the intention of avoiding the complexity of a fully coupled thermal, hydraulic and mechanical modelling. In the new model, porosity, permeability, swelling pressure and pathways formation threshold depend on the water saturation. The model is validated on different gas injection experiments with controlled flow rate and controlled pressure. Some experiments are well known in the literature; some are new. In each case, an inverse approach is used to identify the model parameters. The results confirm that, depending on the type of bentonite (MX80, Avonlea, KunigelV1), modelling the gas migration could require the existence of a pressure-induced saturation-depending preferential pathway. In laboratory-scale experiments, the model leads to an accurate evaluation of the long-term gas migration trends, including not just the gas migration stage but also the water re-saturation level. In a field-scale experiment, the behaviour of the model in a realistic context is revealed.
A downscaling approach for geological characterization of the Raditladi basin of Mercury
Authors: Mancinelli Paolo , Minelli Francesco , Mondini Alessandro , Pauselli Cristina , Federico Costanzo 
Published: March 2014

Abstract
In this work, we combined multi-scale geological maps of Mercury to produce a new global map where geological units are classified based on albedo, crater density and morphological relationships with other units. To create this map, we used the 250 m/pixel mosaic of images acquired by the narrow- and wide-angle cameras onboard the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft during its orbital phase. The geological mapping is supported by digital terrain model data and surface mineralogical variation from the global mosaic of MESSENGER Mercury Atmospheric and Surface Composition Spectrometer observations. This map comprises the global-scale intercrater plains, smooth plains and Odin-type units as reported in previous studies, as well as units we term bright intercrater plains, Caloris rough ejecta and dark material deposits. We mapped a portion of the Raditladi quadrangle (19–35°N, 106–133°E) at a regional scale at a resolution of 166 m/pixel. We characterized the geological context of the area and evaluated the stratigraphic relationships between the units. To obtain a representative geological section, we analysed and corrected available topographical data. The geological cross-section derived from our regional mapping suggests that volcanic emplacement of Raditladi's inner plains followed the topography of the basin after the deposition of impact-related units (i.e. melts, breccias and rim collapse) and was driven by low-viscosity flows. Hollows that appear on Raditladi's peak ring were possibly formed from low-reflectance intercrater plains materials exposed through the peak ring unit.

Supplementary material:

Cleaner, larger version of the global-scale geological map and a local-scale map for comparison are available at
http://www.geolsoc.org.uk/SUP18741
.
Ethical, Social and Economic Issues in Familial Breast Cancer: A Compilation of Views from the E.C. Biomed II Demonstration Project
Authors: Steel Michael , Smyth Elizabeth , Vasen Hans , Eccles Diana , Evans Gareth , Møller Pål , Hodgson Shirley , Stoppa-Lyonnet Dominique , Chang-Claude Jenny , Caligo Maria , Morrison Patrick , Haites Neva 
Published: March 2014

Demand for clinical services for familial breast cancer is continuing to rise across Europe. Service provision is far from uniform and, in most centres, its evolution has been determined by local conditions, specifically by local research interests, rather than by central planning. However, in a number of countries there is evidence of progress towards co‐ordinated development and audit of clinics providing risk assessment, counselling, screening and, in some cases, prophylactic intervention. Much important information should emerge from continued observation and comparative assessment of these developments.In most countries for which relevant data are available, there is a distinct bias towards higher social class among those who avail themselves of clinic facilities (in line with findings from many other health‐promotion initiatives). This should be addressed when considering future organisation of clinical services.Molecular genetic studies designed to identify the underlying mutations responsible for familial breast cancer are not generally regarded as part of the clinical service and are funded through research grants (if at all). Economic considerations suggest that there is a case for keeping this policy under review.Familial cancers throw into sharp relief certain ethical and legal issues that have received much recent attention from government advisory bodies, patients’ representatives, professional commentators and the popular media. Two are of particular importance; first, the right to gain access to medical records of relatives, in order to provide accurate risk assessment for a given family member, versus the right to privacy in respect of personal medical information and, second, the obligation (or otherwise) to inform family members of their risk status if they have not actively sought that knowledge. The legal position seems to vary from country to country and, in many cases, is unclear. In view of pressures to establish uniform approaches to medical confidentiality across the EC, it is important to evaluate the experience of participants in this Demonstration Programme and to apply the principle of “non‐malfeasance” in formulating regu‐lations that should govern future practice in this field.Data on economic aspects of familial breast cancer are remarkably sparse and outdated. As evidence accrues on the influence of screening and intervention programmes on morbidity and mortality, there is a strong case for evaluating the cost‐effectiveness of different models of service provision.
Costs and Benefits of Diagnosing Familial Breast Cancer
Authors: Heimdal Ketil , Mæhle Lovise , Møller Pål 
Published: March 2014

Based on results from our surveillance program for women at risk for inherited breast cancer, we have calculated cost per year earned. Norwegian National Insurance Service reimbursement fees were used in the calculations. The calculated costs are based on empirical figures for expanding already established medical genetic departments and diagnostic outpatient clinics to undertake the work described. Cost per year earned was estimated at Euro 753 using our current practice of identifying the high‐risk women through a traditional cancer family clinic.A strategy of identifying the high‐risk families through genetic testing of all incident breast and ovarian cancers for founder mutations in BRCA1, will increase the cost to Euro 832. Costs related more to genetic counseling and clinical follow‐up than to laboratory procedures. This potential economic limiting factor coincides with a shortage of personnel trained in genetic counseling. The number of relatives counseled to identify one healthy female mutation carrier (i.e. the uptake of genetic testing) is more important to cost‐effectiveness than family size. Costs will vary depending upon the penetrance of the mutations detected and the prevalence of founder mutations in the population examined. Prevalences of BRCA1 founder mutations in some high incidence areas of Norway may be sufficiently high to consider population screening. Unlike mutation screening of cancer genes, founder mutation analysis will not identify DNA variants of uncertain clinical significance. Identification of high‐risk families through founder mutation analysis of BRCA1 ensures that families with maximum risks are given first access to the limited resources of the high‐risk clinics. This may be the greatest contribution to increased cost effectiveness of such a strategy.The assumptions underlying the calculations are discussed. The conclusion is that inherited breast cancer may be managed effectively for the cost of Euro 750–1,600 per year earned.
Genetic Counselling and Testing for Hereditary Breast and Ovarian Cancer: The Gent(le) Approach
Authors: De Vos M. , Poppe B. , Delvaux I. , Mortier G. , Claes K. , Messiaen L. , De Paepe A. 
Published: March 2014

The counselling experience with 50 Flemish families in whom mutation analysis of the total coding region of the BRCA1 and BRCA2 gene has been initiated, is presented.Genetic testing for breast‐ovarian cancer susceptibility is offered by a multidisciplinary team. During the counselling sessions, special attention is given to comprehensible and emotionally acceptable communi‐cation of genetic information and to the psychosocial evaluation of the counselee. The limitations of molecular testing and the controversy surrounding cancer prevention strategies are also discussed.The overall acceptance of mutation testing is high. Some of the problems encountered are inaccuracy of the reported family history, poor retrieval of the medical records of affected family members and the reluctance of many patients to inform their relatives about the possibility of being tested.
Menstrual Cycle Dependent Variability for Serum Tumor Markers CEA, AFP, CA 19‐9, CA 125 and CA 15‐3 in Healthy Women
Authors: Erbağci Ayşe Binnur , Yilmaz Necat , Kutlar Irfan 
Published: March 2014

Information on menstrual cycle dependent variation of tumor markers in healthy women is a subject of diagnostic efficiency and has an impact in elucidating the normal function of these markers. In this study midfollicular and midluteal concentrations of serum CEA, AFP, CA 19‐9, CA 125, CA 15‐3 and their relations with LH, FSH, prolactin, estradiol and progesterone were evaluated during ovulatory cycles in a group of 23 healthy female individuals. Samples were collected on the 7th and 21st day of the same menstrual cycle. Tumor marker and hormone concentrations were determined with chemiluminescence or electrochemiluminescence EIA methods. A significant phase‐dependent difference was observed for CA 15‐3, midluteal concentrations (mean ± SEM; 26.33 ± 1.56 U/ml) higher than the midfollicular (mean ± SEM; 19.27 ± 1.49 U/ml) concentrations (p < 0.001). But an obvious difference for other tumor markers investigated did not exist. Significant correlations of follicular and luteal CA 125 levels with body mass index of the subjects were observed (r:0.52, p < 0.05 and r:0.57, p < 0.005, respectively).CA 15‐3 antigen is a product of the MUC‐1 gene which is expressed in abundance by endometrial epithelial cells in the secretory phase of the menstrual cycle which may be the potential source of variability. The association of CA 125 levels with obesity suggests a possible role of adipose tissue in CA 125 metabolism. In conclusion our data suggest that in healthy women serum CA 15‐3 levels are significantly elevated in the midluteal phase of the menstrual cycle compared to midfollicular phase. Therefore, consideration of menstrual cycle dependent variability for CA 15‐3 appears indicated in interpretation of individual results.