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Showing papers by "Laval University published in 2013"


Journal ArticleDOI
TL;DR: Mindfulness-based therapy is an effective treatment for a variety of psychological problems, and is especially effective for reducing anxiety, depression, and stress.

1,491 citations


Journal ArticleDOI
TL;DR: This review provides an overview of the phenomenon of vaccine Hesitancy and suggests the possible causes of the apparent increase in vaccine hesitancy in the developed world.
Abstract: Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and an increasing risk of vaccine-preventable disease outbreaks and epidemics. This review provides an overview of the phenomenon of vaccine hesitancy. First, we will characterize vaccine hesitancy and suggest the possible causes of the apparent increase in vaccine hesitancy in the developed world. Then we will look at determinants of individual decision-making about vaccination.

1,356 citations


Journal ArticleDOI
22 May 2013-Nature
TL;DR: The draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm, is presented, revealing numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs, which opens up new genomic avenues for conifer forestry and breeding.
Abstract: Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.

1,299 citations


Journal ArticleDOI
TL;DR: A meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, and identified 29,807 SNPs for further genotyping suggests that more than 1,000 additional loci are involved in breast cancer susceptibility.
Abstract: Breast cancer is the most common cancer among women Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC) The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10(-8)) Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility

1,048 citations


Journal ArticleDOI
TL;DR: This review aims to provide a comprehensive overview of current scientific knowledge on FCR and to formulate recommendations for future research to stimulate the research and the development of targeted interventions for cancer survivors and their carers.
Abstract: Purpose Fear of cancer recurrence (FCR) is among the most commonly reported problems and one of the most prevalent areas of unmet needs for cancer survivors and their carers. This review aims to provide a comprehensive overview of current scientific knowledge on FCR and to formulate recommendations for future research.

814 citations


Journal ArticleDOI
TL;DR: This comprehensive article reviews these adverse events of systemic corticosteroid therapy and provides practical recommendations for their prevention and management based on both current literature and the clinical experience of the authors.
Abstract: Systemic corticosteroids play an integral role in the management of many inflammatory and immunologic conditions, but these agents are also associated with serious risks. Osteoporosis, adrenal suppression, hyperglycemia, dyslipidemia, cardiovascular disease, Cushing’s syndrome, psychiatric disturbances and immunosuppression are among the more serious side effects noted with systemic corticosteroid therapy, particularly when used at high doses for prolonged periods. This comprehensive article reviews these adverse events and provides practical recommendations for their prevention and management based on both current literature and the clinical experience of the authors.

781 citations



Journal ArticleDOI
Keith Bradnam1, Joseph Fass1, Anton Alexandrov, Paul Baranay2, Michael Bechner, Inanc Birol, Sébastien Boisvert3, Jarrod Chapman4, Guillaume Chapuis5, Guillaume Chapuis6, Rayan Chikhi6, Rayan Chikhi5, Hamidreza Chitsaz7, Wen-Chi Chou8, Jacques Corbeil3, Cristian Del Fabbro9, T. Roderick Docking, Richard Durbin10, Dent Earl11, Scott J. Emrich12, Pavel Fedotov, Nuno A. Fonseca13, Ganeshkumar Ganapathy14, Richard A. Gibbs15, Sante Gnerre16, Elenie Godzaridis3, Steve Goldstein, Matthias Haimel13, Giles Hall16, David Haussler11, Joseph B. Hiatt17, Isaac Ho4, Jason T. Howard14, Martin Hunt10, Shaun D. Jackman, David B. Jaffe16, Erich D. Jarvis14, Huaiyang Jiang15, Sergey Kazakov, Paul J. Kersey13, Jacob O. Kitzman17, James R. Knight, Sergey Koren18, Tak-Wah Lam, Dominique Lavenier5, Dominique Lavenier6, François Laviolette3, Yingrui Li, Zhenyu Li, Binghang Liu, Yue Liu15, Ruibang Luo, Iain MacCallum16, Matthew D. MacManes19, Nicolas Maillet6, Sergey Melnikov, Bruno Vieira20, Delphine Naquin6, Zemin Ning10, Thomas D. Otto10, Benedict Paten11, Octávio S. Paulo20, Adam M. Phillippy18, Francisco Pina-Martins20, Michael Place, Dariusz Przybylski16, Xiang Qin15, Carson Qu15, Filipe J. Ribeiro16, Stephen Richards15, Daniel S. Rokhsar4, Daniel S. Rokhsar19, J. Graham Ruby21, J. Graham Ruby22, Simone Scalabrin9, Michael C. Schatz23, David C. Schwartz, Alexey Sergushichev, Ted Sharpe16, Timothy I. Shaw8, Jay Shendure17, Yujian Shi, Jared T. Simpson10, Henry Song15, Fedor Tsarev, Francesco Vezzi24, Riccardo Vicedomini9, Jun Wang, Kim C. Worley15, Shuangye Yin16, Siu-Ming Yiu, Jianying Yuan, Guojie Zhang, Hao Zhang, Shiguo Zhou, Ian F Korf1 
TL;DR: The Assemblathon 2 as mentioned in this paper presented a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and a snake) from 21 participating teams.
Abstract: Background - The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results - In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. Conclusions - Many current genome assemblers produced useful assemblies, containing a significant representation of their genes, regulatory sequences, and overall genome structure. However, the high degree of variability between the entries suggests that there is still much room for improvement in the field of genome assembly and that approaches which work well in assembling the genome of one species may not necessarily work well for another.

690 citations


Journal ArticleDOI
TL;DR: The Canadian Hypertension Education Program reviews the hypertension literature annually and provides detailed recommendations regarding hypertension diagnosis, assessment, prevention, and treatment, and 4 new recommendations were added and 2 existing recommendations were modified this year.

683 citations


Journal ArticleDOI
TL;DR: The current state of knowledge about axonal transport defects that might contribute to the pathogenesis of particular neurodegenerative diseases are reviewed.
Abstract: The intracellular transport of organelles along an axon is crucial for the maintenance and function of a neuron. Anterograde axonal transport has a role in supplying proteins and lipids to the distal synapse and mitochondria for local energy requirements, whereas retrograde transport is involved in the clearance of misfolded and aggregated proteins from the axon and the intracellular transport of distal trophic signals to the soma. Axonal transport can be affected by alterations to various components of the transport machinery. Here, we review the current state of knowledge about axonal transport defects that might contribute to the pathogenesis of particular neurodegenerative diseases.

655 citations


Journal ArticleDOI
TL;DR: It is revealed that MI consistently recruits a large fronto-parietal network in addition to subcortical and cerebellar regions, the first quantitative cortical map of MI, and methodological issues that should be addressed in future research are highlighted.

Journal ArticleDOI
TL;DR: The three essential elements of shared decision making are described: recognizing and acknowledging that a decision is required; knowing and understanding the best available evidence; and incorporating the patient's values and preferences into the decision.
Abstract: For many patients, the time spent meeting with their physician—the clinical encounter—is the most opportune moment for them to become engaged in their own health through the process of shared decision making. In the United States shared decision making is being promoted for its potential to improve the health of populations and individual patients, while also helping control care costs. In this overview we describe the three essential elements of shared decision making: recognizing and acknowledging that a decision is required; knowing and understanding the best available evidence; and incorporating the patient’s values and preferences into the decision. To achieve the promise of shared decision making, more physicians need training in the approach, and more practices need to be reorganized around the principles of patient engagement. Additional research is also needed to identify the interventions that are most effective.

Journal ArticleDOI
Keith Bradnam, Joseph Fass, Anton Alexandrov, Paul Baranay1, Michael Bechner, Inanc Birol2, Sébastien Boisvert3, Jarrod Chapman4, Guillaume Chapuis5, Guillaume Chapuis6, Rayan Chikhi6, Rayan Chikhi5, Hamidreza Chitsaz7, Wen-Chi Chou8, Jacques Corbeil3, Cristian Del Fabbro, Roderick R. Docking2, Richard Durbin9, Dent Earl10, Scott J. Emrich11, Pavel Fedotov, Nuno A. Fonseca12, Ganeshkumar Ganapathy13, Richard A. Gibbs14, Sante Gnerre15, Elenie Godzaridis3, Steve Goldstein, Matthias Haimel12, Giles Hall15, David Haussler10, Joseph B. Hiatt16, Isaac Ho4, Jason T. Howard13, Martin Hunt9, Shaun D. Jackman2, David B. Jaffe15, Erich D. Jarvis13, Huaiyang Jiang14, Sergey Kazakov, Paul J. Kersey12, Jacob O. Kitzman16, James R. Knight, Sergey Koren17, Tak-Wah Lam18, Dominique Lavenier6, Dominique Lavenier5, Dominique Lavenier19, François Laviolette3, Yingrui Li18, Zhenyu Li, Binghang Liu, Yue Liu14, Ruibang Luo18, Iain MacCallum15, Matthew D. MacManes20, Nicolas Maillet5, Nicolas Maillet19, Sergey Melnikov, Delphine Naquin5, Delphine Naquin19, Zemin Ning9, Thomas D. Otto9, Benedict Paten10, Octávio S. Paulo21, Adam M. Phillippy17, Francisco Pina-Martins21, Michael Place, Dariusz Przybylski15, Xiang Qin14, Carson Qu14, Filipe J. Ribeiro, Stephen Richards14, Daniel S. Rokhsar22, Daniel S. Rokhsar4, J. Graham Ruby23, J. Graham Ruby24, Simone Scalabrin, Michael C. Schatz25, David C. Schwartz, Alexey Sergushichev, Ted Sharpe15, Timothy I. Shaw8, Jay Shendure16, Yujian Shi, Jared T. Simpson9, Henry Song14, Fedor Tsarev, Francesco Vezzi26, Riccardo Vicedomini27, Bruno Vieira21, Jun Wang, Kim C. Worley14, Shuangye Yin15, Siu-Ming Yiu18, Jianying Yuan, Guojie Zhang, Hao Zhang, Shiguo Zhou, Ian F Korf 
TL;DR: The Assemblathon 2 as discussed by the authors presented a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and a snake) from 21 participating teams.
Abstract: Background: The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results: In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. (Continued on next page)

Journal ArticleDOI
TL;DR: The present report provides the first definition of a “Cognitive Frailty” condition in older adults and proposes the use of multidomain interventions focused on the physical, nutritional, cognitive and psychological domains for improving the well-being and quality of life in the elderly.
Abstract: The frailty syndrome has recently attracted attention of the scientific community and public health organizations as precursor and contributor of age-related conditions (particularly disability) in older persons. In parallel, dementia and cognitive disorders also represent major healthcare and social priorities. Although physical frailty and cognitive impairment have shown to be related in epidemiological studies, their pathophysiological mechanisms have been usually studied separately. An International Consensus Group on "Cognitive Frailty" was organized by the International Academy on Nutrition and Aging (I.A.N.A) and the International Association of Gerontology and Geriatrics (I.A.G.G) on April 16th, 2013 in Toulouse (France). The present report describes the results of the Consensus Group and provides the first definition of a "Cognitive Frailty" condition in older adults. Specific aim of this approach was to facilitate the design of future personalized preventive interventions in older persons. Finally, the Group discussed the use of multidomain interventions focused on the physical, nutritional, cognitive and psychological domains for improving the well-being and quality of life in the elderly. The consensus panel proposed the identification of the so-called "cognitive frailty" as an heterogeneous clinical manifestation characterized by the simultaneous presence of both physical frailty and cognitive impairment. In particular, the key factors defining such a condition include: 1) presence of physical frailty and cognitive impairment (CDR=0.5); and 2) exclusion of concurrent AD dementia or other dementias. Under different circumstances, cognitive frailty may represent a precursor of neurodegenerative processes. A potential for reversibility may also characterize this entity. A psychological component of the condition is evident and concurs at increasing the vulnerability of the individual to stressors.

Journal ArticleDOI
TL;DR: The various tactics that are used by phages to overcome bacterial resistance mechanisms, including adsorption inhibition, restriction–modification, CRISPR–Cas (clustered regularly interspaced short palindromic repeats–CRISPR-associated proteins) systems and abortive infection are described.
Abstract: Bacteria and their viral predators (bacteriophages) are locked in a constant battle. In order to proliferate in phage-rich environments, bacteria have an impressive arsenal of defence mechanisms, and in response, phages have evolved counter-strategies to evade these antiviral systems. In this Review, we describe the various tactics that are used by phages to overcome bacterial resistance mechanisms, including adsorption inhibition, restriction-modification, CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) systems and abortive infection. Furthermore, we consider how these observations have enhanced our knowledge of phage biology, evolution and phage-host interactions.

Journal ArticleDOI
TL;DR: The connections between mTORC1 and gene transcription are reviewed by focusing on its impact in regulating the activation of specific transcription factors including including STAT3, SREBPs, PParγ, PPARα, HIF1α, YY1–PGC1α and TFEB.
Abstract: The mechanistic (or mammalian) target of rapamycin (mTOR) is a kinase that regulates key cellular functions linked to the promotion of cell growth and metabolism. This kinase, which is part of two protein complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2), has a fundamental role in coordinating anabolic and catabolic processes in response to growth factors and nutrients. Of the two mTOR complexes, mTORC1 is by far the best characterized. When active, mTORC1 triggers cell growth and proliferation by promoting protein synthesis, lipid biogenesis, and metabolism, and by reducing autophagy. The fact that mTORC1 deregulation is associated with several human diseases, such as type 2 diabetes, cancer, obesity and neurodegeneration, highlights its importance in the maintenance of cellular homeostasis. Over the last years, several groups observed that mTORC1 inhibition, in addition to reducing protein synthesis, deeply affects gene transcription. Here, we review the connections between mTORC1 and gene transcription by focusing on its impact in regulating the activation of specific transcription factors including including STAT3, SREBPs, PPARγ, PPARα, HIF1α, YY1–PGC1α and TFEB. We also discuss the importance of these transcription factors in mediating the effects of mTORC1 on various cellular processes in physiological and pathological contexts.

Journal ArticleDOI
Stig E. Bojesen1, Stig E. Bojesen2, Karen A. Pooley3, Sharon E. Johnatty4  +452 moreInstitutions (129)
TL;DR: Using the Illumina custom genotyping array iCOGs, SNPs at the TERT locus in breast, ovarian and BRCA1 mutation carrier cancer cases and controls and leukocyte telomere measurements are analyzed to find associations cluster into three independent peaks.
Abstract: TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 x 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 x 10(-8)) and BRCA1 mutation carrier (P = 1.1 x 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 x 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 x 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 x 10(-12)) and BRCA1 mutation carrier (P = 1.6 x 10-14) breast and invasive ovarian (P = 1.3 x 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.

Journal ArticleDOI
TL;DR: Symptomatic CO following TAVI was a rare but life-threatening complication that occurred more frequently in women, in patients receiving a balloon-expandable valve, and in those with a previous surgical bioprosthesis, highlighting the importance of anticipating and preventing the occurrence of this complication.

Journal ArticleDOI
TL;DR: Relaxed patient selection criteria, improved clinical management of hearing loss, modifications of surgical practice, and improved devices may explain the differences.
Abstract: Objective: To update a 15-year-old study of 800 postlinguistically deaf adult patients showing how duration of severe to profound hearing loss, age at cochlear implantation (CI), age at onset of severe to profound hearing loss, etiology and CI experience affected CI outcome. Study Design: Retrospective multicenter study. Methods: Data from 2251 adult patients implanted since 2003 in 15 international centers were collected and speech scores in quiet were converted to percentile ranks to remove differences between centers. Results: The negative effect of long duration of severe to profound hearing loss was less important in the new data than in 1996; the effects of age at CI and age at onset of severe to profound hearing loss were delayed until older ages; etiology had a smaller effect, and the effect of CI experience was greater with a steeper learning curve. Patients with longer durations of severe to profound hearing loss were less likely to improve with CI experience than patients with shorter duration of severe to profound hearing loss. Conclusions: The factors that were relevant in 1996 were still relevant in 2011, although their relative importance had changed. Relaxed patient selection criteria, improved clinical management of hearing loss, modifications of surgical practice, and improved devices may explain the differences.

Journal ArticleDOI
Olivier Boiral1
TL;DR: In this article, the authors examine the extent to which sustainability reporting can be viewed as a simulacrum used to camouflage real sustainable development problems and project an idealized view of the firms' situations.
Abstract: Purpose – The purpose of this paper is to examine the extent to which sustainability reporting can be viewed as a simulacrum used to camouflage real sustainable-development problems and project an idealized view of the firms' situations. Design/methodology/approach – The method was based on the content analysis and counter accounting of 23 sustainability reports from firms in the energy and mining sectors which had received application levels of A or A+ from the Global Reporting Initiative (GRI). The information disclosed in some 2,700 pages of reports was structured around 92 GRI indicators and compared with 116 significant news events that clearly addressed the responsibility of these firms in sustainable development problems. Moreover, the 1,258 pictures included in sustainability reports were categorized into recurring themes from an inductive perspective. Findings – A total of 90 per cent of the significant negative events were not reported, contrary to the principles of balance, completeness and tra...

Journal ArticleDOI
TL;DR: It is demonstrated that LVOT calcification and aggressive annular area oversizing are associated with an increased risk of aortic root rupture during TAVR with balloon-expandable prostheses.
Abstract: Background—Aortic root rupture is a major concern with balloon-expandable transcatheter aortic valve replacement (TAVR). We sought to identify predictors of aortic root rupture during balloon-expandable TAVR by using multidetector computed tomography. Methods and Results—Thirty-one consecutive patients who experienced left ventricular outflow tract (LVOT)/annular/aortic contained/noncontained rupture during TAVR were collected from 16 centers. A caliper-matched sample of 31 consecutive patients without annular rupture, who underwent pre-TAVR multidetector computed tomography served as a control group. Multidetector computed tomography assessment included short- and long-axis diameters and cross-sectional area of the sinotubular junction, annulus, and LVOT, and the presence, location, and extent of calcification of the LVOT, as well. There were no significant differences between the 2 groups in any preoperative clinical and echocardiographic variables. Aortic root rupture was identified in 20 patients and ...

Journal ArticleDOI
TL;DR: This review discusses recent data on the early colonization of the gut by microbial species, development of the intestinal microbiota, and its impact on health.

Journal ArticleDOI
23 Jan 2013-PLOS ONE
TL;DR: The approach to obtain high quality SNPs developed here will be helpful for marker assisted genomics as well as assessment of available genetic resources for effective utilisation in a wide number of species.
Abstract: Highly parallel SNP genotyping platforms have been developed for some important crop species, but these platforms typically carry a high cost per sample for first-time or small-scale users. In contrast, recently developed genotyping by sequencing (GBS) approaches offer a highly cost effective alternative for simultaneous SNP discovery and genotyping. In the present investigation, we have explored the use of GBS in soybean. In addition to developing a novel analysis pipeline to call SNPs and indels from the resulting sequence reads, we have devised a modified library preparation protocol to alter the degree of complexity reduction. We used a set of eight diverse soybean genotypes to conduct a pilot scale test of the protocol and pipeline. Using ApeKI for GBS library preparation and sequencing on an Illumina GAIIx machine, we obtained 5.5 M reads and these were processed using our pipeline. A total of 10,120 high quality SNPs were obtained and the distribution of these SNPs mirrored closely the distribution of gene-rich regions in the soybean genome. A total of 39.5% of the SNPs were present in genic regions and 52.5% of these were located in the coding sequence. Validation of over 400 genotypes at a set of randomly selected SNPs using Sanger sequencing showed a 98% success rate. We then explored the use of selective primers to achieve a greater complexity reduction during GBS library preparation. The number of SNP calls could be increased by almost 40% and their depth of coverage was more than doubled, thus opening the door to an increase in the throughput and a significant decrease in the per sample cost. The approach to obtain high quality SNPs developed here will be helpful for marker assisted genomics as well as assessment of available genetic resources for effective utilisation in a wide number of species.


Journal ArticleDOI
TL;DR: The clinical yield of AVC quantification by MDCT to diagnose and manage these complex patients is emphasized, with at least one-half of the patients with discordant low gradient present with heavy AVC-load reflective of severe calcified aortic valve disease.

Journal ArticleDOI
Fergus J. Couch1, Xianshu Wang1, Lesley McGuffog2, Andy C. H. Lee2  +258 moreInstitutions (100)
TL;DR: It is estimated that the breast cancer lifetime risks for the5% of BRCA1 carriers at lowest risk are 28%–50% compared to 81%–100% for the 5% at highest risk, and the ovarian cancer lifetime risk is 63% or higher, based on the known cancer risk-modifying loci.
Abstract: BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.

Journal ArticleDOI
TL;DR: In this article, the authors explored the relationship between energy balance closure and landscape heterogeneity using MODIS products and GLOBEstat elevation data and found that landscape-level heterogeneity in vegetation and topography cannot be ignored as a contributor to incomplete energy balance closures at the surface-atmosphere exchange measurements.

Journal ArticleDOI
TL;DR: SNPs at four loci were associated with ER-negative but not ER-positive breast cancer (P > 0.05), providing further evidence for distinct etiological pathways associated with invasive ER- positive and ER- negative breast cancers.
Abstract: Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

Journal ArticleDOI
TL;DR: In this article, an integrative review of meta-standards is presented, focusing on the two main metastandards which have been adopted by more than 1.3 million organizations worldwide: ISO 14001 and ISO 9001.
Abstract: Management system standards, also called meta-standards, have been adopted by an increasing number of organizations across the world. Although these management system standards are based on the same type of management principles and institutional arrangements, the literature remains scattered, with diverse studies focused on specific standards and published in various journals. The main objective of this paper is to analyse the academic research on meta-standards through an integrative review intended to shed light on the main conclusions and substantial advances made in this area. This integrative review focuses more specifically on the two main meta-standards which have been adopted by more than 1.3 million organizations worldwide: ISO 14001 and ISO 9001. The paper contributes insights into the main streams of the literature and current knowledge gaps to be addressed in future research on the various issues related to meta-standards: global governance, diffusion processes, motivations, benefits of adoption and impacts on performance, internalization, integration, consultancy and auditing.

Journal ArticleDOI
TL;DR: Single-dose intravenous and multiple-dose subcutaneous benralizumab reduced eosinophil counts in airway mucosa/submucosa and sputum and suppressed eosInophils counts in bone marrow and peripheral blood and the safety profile supports further development.
Abstract: Background Many asthmatic patients exhibit sputum eosinophilia associated with exacerbations. Benralizumab targets eosinophils by binding IL-5 receptor α, inducing apoptosis through antibody-dependent cell-mediated cytotoxicity. Objectives We sought to evaluate the safety of benralizumab in adults with eosinophilic asthma and its effects on eosinophil counts in airway mucosal/submucosal biopsy specimens, sputum, bone marrow, and peripheral blood. Methods In this multicenter, double-blind, placebo-controlled phase I study, 13 subjects were randomized to single-dose intravenous placebo or 1 mg/kg benralizumab (day 0; cohort 1), and 14 subjects were randomized to 3 monthly subcutaneous doses of placebo or 100 or 200 mg of benralizumab (days 0, 28, and 56; cohort 2). Cohorts 1 and 2 were consecutive. Results The incidence of adverse events was similar between groups. No serious adverse events related to benralizumab occurred. In cohort 1 intravenous benralizumab produced a median decrease from baseline of 61.9% in airway mucosal eosinophil counts (day 28; placebo: +19.6%; P = .28), as well as an 18.7% decrease (day 21) in sputum and a 100% decrease (day 28) in blood counts. Eosinophils were not detectable in bone marrow of benralizumab-treated subjects (day 28, n = 4). In cohort 2 subcutaneous benralizumab demonstrated a combined (100 + 200 mg) median reduction of 95.8% in airway eosinophil counts (day 84; placebo, 46.7%; P = .06), as well as an 89.9% decrease (day 28) in sputum and a 100% decrease (day 84) in blood counts. Conclusion Single-dose intravenous and multiple-dose subcutaneous benralizumab reduced eosinophil counts in airway mucosa/submucosa and sputum and suppressed eosinophil counts in bone marrow and peripheral blood. The safety profile supports further development. Additional studies are needed to assess the clinical benefit in asthmatic patients.