Showing papers by "Laval University published in 2012"

Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus.

Abstract: Objective The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new knowledge regarding the immunology of SLE. Methods The classification criteria were derived from a set of 702 expert-rated patient scenarios. Recursive partitioning was used to derive an initial rule that was simplified and refined based on SLICC physician consensus. The SLICC group validated the classification criteria in a new validation sample of 690 new expert-rated patient scenarios. Results Seventeen criteria were identified. In the derivation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (49 versus 70; P = 0.0082) and had greater sensitivity (94% versus 86%; P < 0.0001) and equal specificity (92% versus 93%; P = 0.39). In the validation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (62 versus 74; P = 0.24) and had greater sensitivity (97% versus 83%; P < 0.0001) but lower specificity (84% versus 96%; P < 0.0001). Conclusion The new SLICC classification criteria performed well in a large set of patient scenarios rated by experts. According to the SLICC rule for the classification of SLE, the patient must satisfy at least 4 criteria, including at least one clinical criterion and one immunologic criterion OR the patient must have biopsy-proven lupus nephritis in the presence of antinuclear antibodies or antidouble-stranded DNA antibodies. (Less)

Understanding Smart Cities: An Integrative Framework

Abstract: Making a city "smart" is emerging as a strategy to mitigate the problems generated by the urban population growth and rapid urbanization. Yet little academic research has sparingly discussed the phenomenon. To close the gap in the literature about smart cities and in response to the increasing use of the concept, this paper proposes a framework to understand the concept of smart cities. Based on the exploration of a wide and extensive array of literature from various disciplinary areas we identify eight critical factors of smart city initiatives: management and organization, technology, governance, policy context, people and communities, economy, built infrastructure, and natural environment. These factors form the basis of an integrative framework that can be used to examine how local governments are envisioning smart city initiatives. The framework suggests directions and agendas for smart city research and outlines practical implications for government professionals.

DEAP: evolutionary algorithms made easy

Abstract: DEAP is a novel evolutionary computation framework for rapid prototyping and testing of ideas. Its design departs from most other existing frameworks in that it seeks to make algorithms explicit and data structures transparent, as opposed to the more common black-box frameworks. Freely available with extensive documentation at http://deap.gel.ulaval.ca, DEAP is an open source project under an LGPL license.

Basal insulin and cardiovascular and other outcomes in dysglycemia

Abstract: BACKGROUND: The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested. METHODS: We randomly assigned 12,537 people (mean age, 63.5 years) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes to receive insulin glargine (with a target fasting blood glucose level of ≤95 mg per deciliter [5.3 mmol per liter]) or standard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design. The results of the comparison between insulin glargine and standard care are reported here. The coprimary outcomes were nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure. Microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers were also compared between groups. RESULTS: The median follow-up was 6.2 years (interquartile range, 5.8 to 6.7). Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, for the first coprimary outcome (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P=0.63) and 5.52 and 5.28 per 100 person-years, respectively, for the second coprimary outcome (hazard ratio, 1.04; 95% CI, 0.97 to 1.11; P=0.27). New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64 to 1.00; P=0.05). Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years. Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the standard-care group. There was no significant difference in cancers (hazard ratio, 1.00; 95% CI, 0.88 to 1.13; P=0.97). CONCLUSIONS: When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers. Although it reduced new-onset diabetes, insulin glargine also increased hypoglycemia and modestly increased weight. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).

The Consensus Sleep Diary: Standardizing Prospective Sleep Self-Monitoring

Abstract: Study objectives: To present an expert consensus, standardized, patient-informed sleep diary. Methods and results: Sleep diaries from the original expert panel of 25 attendees of the Pittsburgh Assessment Conference(1) were collected and reviewed. A smaller subset of experts formed a committee and reviewed the compiled diaries. Items deemed essential were included in a Core sleep diary, and those deemed optional were retained for an expanded diary. Secondly, optional items would be available in other versions. A draft of the Core and optional versions along with a feedback questionnaire were sent to members of the Pittsburgh Assessment Conference. The feedback from the group was integrated and the diary drafts were subjected to 6 focus groups composed of good sleepers, people with insomnia, and people with sleep apnea. The data were summarized into themes and changes to the drafts were made in response to the focus groups. The resultant draft was evaluated by another focus group and subjected to lexile analyses. The lexile analyses suggested that the Core diary instructions are at a sixth-grade reading level and the Core diary was written at a third-grade reading level. Conclusions: The Consensus Sleep Diary was the result of collaborations with insomnia experts and potential users. The adoption of a standard sleep diary for insomnia will facilitate comparisons across studies and advance the field. The proposed diary is intended as a living document which still needs to be tested, refined, and validated.

Global asthma prevalence in adults: findings from the cross-sectional world health survey

Abstract: Asthma is a major cause of disability, health resource utilization and poor quality of life world-wide. We set out to generate estimates of the global burden of asthma in adults, which may inform the development of strategies to address this common disease. The World Health Survey (WHS) was developed and implemented by the World Health Organization in 2002-2003. A total of 178,215 individuals from 70 countries aged 18 to 45 years responded to questions related to asthma and related symptoms. The prevalence of asthma was based on responses to questions relating to self-reported doctor diagnosed asthma, clinical/treated asthma, and wheezing in the last 12 months. The global prevalence rates of doctor diagnosed asthma, clinical/treated asthma and wheezing in adults were 4.3%, 4.5%, and 8.6% respectively, and varied by as much as 21-fold amongst the 70 countries. Australia reported the highest rate of doctor diagnosed, clinical/treated asthma, and wheezing (21.0%, 21.5%, and 27.4%). Amongst those with clinical/treated asthma, almost 24% were current smokers, half reported wheezing, and 20% had never been treated for asthma. This study provides a global estimate of the burden of asthma in adults, and suggests that asthma continues to be a major public health concern worldwide. The high prevalence of smoking remains a major barrier to combating the global burden of asthma. While the highest prevalence rates were observed in resource-rich countries, resource-poor nations were also significantly affected, posing a barrier to development as it stretches further the demands of non-communicable diseases.

Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans

Abstract: Brown adipose tissue (BAT) is vital for proper thermogenesis during cold exposure in rodents, but until recently its presence in adult humans and its contribution to human metabolism were thought to be minimal or insignificant. Recent studies using PET with 18F-fluorodeoxyglucose (18FDG) have shown the presence of BAT in adult humans. However, whether BAT contributes to cold-induced nonshivering thermogenesis in humans has not been proven. Using PET with 11C-acetate, 18FDG, and 18F-fluoro-thiaheptadecanoic acid (18FTHA), a fatty acid tracer, we have quantified BAT oxidative metabolism and glucose and nonesterified fatty acid (NEFA) turnover in 6 healthy men under controlled cold exposure conditions. All subjects displayed substantial NEFA and glucose uptake upon cold exposure. Furthermore, we demonstrated cold-induced activation of oxidative metabolism in BAT, but not in adjoining skeletal muscles and subcutaneous adipose tissue. This activation was associated with an increase in total energy expenditure. We found an inverse relationship between BAT activity and shivering. We also observed an increase in BAT radio density upon cold exposure, indicating reduced BAT triglyceride content. In sum, our study provides evidence that BAT acts as a nonshivering thermogenesis effector in humans.

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Abstract: Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

Shared decision making: really putting patients at the centre of healthcare

Abstract: Although many clinicians feel they already use shared decision making, research shows a perception-reality gap. A M Stiggelbout and colleagues discuss why it is important and highlight some best practices

Perceiving the epigenetic landscape through histone readers

Abstract: Post-translational modifications (PTMs) of histones provide a fine-tuned mechanism for regulating chromatin structure and dynamics. PTMs can alter direct interactions between histones and DNA and serve as docking sites for protein effectors, or readers, of these PTMs. Binding of the readers recruits or stabilizes various components of the nuclear signaling machinery at specific genomic sites, mediating fundamental DNA-templated processes, including gene transcription and DNA recombination, replication and repair. In this review, we highlight the latest advances in characterizing histone-binding mechanisms and identifying new epigenetic readers and summarize the functional significance of PTM recognition.

Innate Lymphoid Cells Promote Anatomical Containment of Lymphoid-Resident Commensal Bacteria

Abstract: The mammalian intestinal tract is colonized by trillions of beneficial commensal bacteria that are anatomically restricted to specific niches. However, the mechanisms that regulate anatomical containment remain unclear. Here, we show that interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) are present in intestinal tissues of healthy mammals. Depletion of ILCs resulted in peripheral dissemination of commensal bacteria and systemic inflammation, which was prevented by administration of IL-22. Disseminating bacteria were identified as Alcaligenes species originating from host lymphoid tissues. Alcaligenes was sufficient to promote systemic inflammation after ILC depletion in mice, and Alcaligenes-specific systemic immune responses were associated with Crohn's disease and progressive hepatitis C virus infection in patients. Collectively, these data indicate that ILCs regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases.

Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies

Abstract: Background Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. Findings The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. Interpretation Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.

Ray Meta: scalable de novo metagenome assembly and profiling

Abstract: Voluminous parallel sequencing datasets, especially metagenomic experiments, require distributed computing for de novo assembly and taxonomic profiling. Ray Meta is a massively distributed metagenome assembler that is coupled with Ray Communities, which profiles microbiomes based on uniquely-colored k-mers. It can accurately assemble and profile a three billion read metagenomic experiment representing 1,000 bacterial genomes of uneven proportions in 15 hours with 1,024 processor cores, using only 1.5 GB per core. The software will facilitate the processing of large and complex datasets, and will help in generating biological insights for specific environments. Ray Meta is open source and available at http://denovoassembler.sf.net.

Terrestrial biosphere models need better representation of vegetation phenology: results from the North American Carbon Program Site Synthesis

Abstract: Phenology, by controlling the seasonal activity of vegetation on the land surface, plays a fundamental role in regulating photosynthesis and other ecosystem processes, as well as competitive interactions and feedbacks to the climate system. We conducted an analysis to evaluate the representation of phenology, and the associated seasonality of ecosystem-scale CO2 exchange, in 14 models participating in the North American Carbon Program Site Synthesis. Model predictions were evaluated using long-term measurements (emphasizing the period 2000–2006) from 10 forested sites within the AmeriFlux and Fluxnet-Canada networks. In deciduous forests, almost all models consistently predicted that the growing season started earlier, and ended later, than was actually observed; biases of 2 weeks or more were

Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities

Abstract: Hypertension affects one billion people and is a principal reversible risk factor for cardiovascular disease. Pseudohypoaldosteronism type II (PHAII), a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis, has revealed previously unrecognized physiology orchestrating the balance between renal salt reabsorption and K(+) and H(+) excretion. Here we used exome sequencing to identify mutations in kelch-like 3 (KLHL3) or cullin 3 (CUL3) in PHAII patients from 41 unrelated families. KLHL3 mutations are either recessive or dominant, whereas CUL3 mutations are dominant and predominantly de novo. CUL3 and BTB-domain-containing kelch proteins such as KLHL3 are components of cullin-RING E3 ligase complexes that ubiquitinate substrates bound to kelch propeller domains. Dominant KLHL3 mutations are clustered in short segments within the kelch propeller and BTB domains implicated in substrate and cullin binding, respectively. Diverse CUL3 mutations all result in skipping of exon 9, producing an in-frame deletion. Because dominant KLHL3 and CUL3 mutations both phenocopy recessive loss-of-function KLHL3 mutations, they may abrogate ubiquitination of KLHL3 substrates. Disease features are reversed by thiazide diuretics, which inhibit the Na-Cl cotransporter in the distal nephron of the kidney; KLHL3 and CUL3 are expressed in this location, suggesting a mechanistic link between KLHL3 and CUL3 mutations, increased Na-Cl reabsorption, and disease pathogenesis. These findings demonstrate the utility of exome sequencing in disease gene identification despite the combined complexities of locus heterogeneity, mixed models of transmission and frequent de novo mutation, and establish a fundamental role for KLHL3 and CUL3 in blood pressure, K(+) and pH homeostasis.

Pathology of Breast and Ovarian Cancers among BRCA1 and BRCA2 Mutation Carriers: Results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).

Abstract: BACKGROUND: Previously, small studies have found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization.METHODS: We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian, and contralateral breast cancers.RESULTS: There was strong evidence that the proportion of estrogen receptor (ER)-negative breast tumors decreased with age at diagnosis among BRCA1 (P-trend = 1.2 × 10(-5)), but increased with age at diagnosis among BRCA2, carriers (P-trend = 6.8 × 10(-6)). The proportion of triple-negative tumors decreased with age at diagnosis in BRCA1 carriers but increased with age at diagnosis of BRCA2 carriers. In both BRCA1 and BRCA2 carriers, ER-negative tumors were of higher histologic grade than ER-positive tumors (grade 3 vs. grade 1; P = 1.2 × 10(-13) for BRCA1 and P = 0.001 for BRCA2). ER and progesterone receptor (PR) expression were independently associated with mutation carrier status [ER-positive odds ratio (OR) for BRCA2 = 9.4, 95% CI: 7.0-12.6 and PR-positive OR = 1.7, 95% CI: 1.3-2.3, under joint analysis]. Lobular tumors were more likely to be BRCA2-related (OR for BRCA2 = 3.3, 95% CI: 2.4-4.4; P = 4.4 × 10(-14)), and medullary tumors BRCA1-related (OR for BRCA2 = 0.25, 95% CI: 0.18-0.35; P = 2.3 × 10(-15)). ER-status of the first breast cancer was predictive of ER-status of asynchronous contralateral breast cancer (P = 0.0004 for BRCA1; P = 0.002 for BRCA2). There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous: 67%; mucinous: 1%; endometrioid: 12%; clear-cell: 2%).Conclusions/Impact: Pathologic characteristics of BRCA1 and BRCA2 tumors may be useful for improving risk-prediction algorithms and informing clinical strategies for screening and prophylaxis. Cancer Epidemiol Biomarkers Prev; 1-14. ©2011 AACR.

A Percutaneous Treatment Algorithm for Crossing Coronary Chronic Total Occlusions

Abstract: Coronary chronic total occlusions (CTOs) are frequently identified during coronary angiography and remain the most challenging lesion group to treat. Patients with CTOs are frequently left unrevascularized due to perceptions of high failure rates and technical complexity even if they have symptoms of coronary disease or ischemia. In this review, the authors describe a North American contemporary approach for percutaneous coronary interventions for CTO. Two guide catheters are placed to facilitate seamless transition between antegrade wire-based, antegrade dissection re-entry-based, and retrograde (wire or dissection re-entry) techniques, the "hybrid" interventional strategy. After dual coronary injection is performed, 4 angiographic parameters are assessed: 1) clear understanding of location of the proximal cap using angiography or intravascular ultrasonography; 2) lesion length; 3) presence of branches, as well as size and quality of the target vessel at the distal cap; and 4) suitability of collaterals for retrograde techniques. On the basis of these 4 characteristics, an initial strategy and rank order hierarchy for technical approaches is established. Radiation exposure, contrast utilization, and procedure time are monitored throughout the procedure, and thresholds are established for intraprocedural strategy conversion to maximize safety, efficiency, and effectiveness.

Allergic Rhinitis and its Impact on Asthma (ARIA): Achievements in 10 years and future needs

Abstract: Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.

Histone phosphorylation: A chromatin modification involved in diverse nuclear events

Abstract: Histone posttranslational modifications are key components of diverse processes that modulate chromatin structure. These marks function as signals during various chromatin-based events, and act as platforms for recruitment, assembly or retention of chromatin-associated factors. The best-known function of histone phosphorylation takes place during cellular response to DNA damage, when phosphorylated histone H2A(X) demarcates large chromatin domains around the site of DNA breakage. However, multiple studies have also shown that histone phosphorylation plays crucial roles in chromatin remodeling linked to other nuclear processes. In this review, we summarize the current knowledge of histone phosphorylation and describe the many kinases and phosphatases that regulate it. We discuss the key roles played by this histone mark in DNA repair, transcription and chromatin compaction during cell division and apoptosis. Additionally, we describe the intricate crosstalk that occurs between phosphorylation and other histone modifications and allows for sophisticated control over the chromatin remodeling processes.

Report of the Task Group 186 on model-based dose calculation methods in brachytherapy beyond the TG-43 formalism: current status and recommendations for clinical implementation.

Abstract: The charge of Task Group 186 (TG-186) is to provide guidance for early adopters of model-based dose calculation algorithms (MBDCAs) for brachytherapy (BT) dose calculations to ensure practice uniformity. Contrary to external beam radiotherapy, heterogeneity correction algorithms have only recently been made available to the BT community. Yet, BT dose calculation accuracy is highly dependent on scatter conditions and photoelectric effect cross-sections relative to water. In specific situations, differences between the current water-based BT dose calculation formalism (TG-43) and MBDCAs can lead to differences in calculated doses exceeding a factor of 10. MBDCAs raise three major issues that are not addressed by current guidance documents: (1) MBDCA calculated doses are sensitive to the dose specification medium, resulting in energy-dependent differences between dose calculated to water in a homogeneous water geometry (TG-43), dose calculated to the local medium in the heterogeneous medium, and the intermediate scenario of dose calculated to a small volume of water in the heterogeneous medium. (2) MBDCA doses are sensitive to voxel-by-voxel interaction cross sections. Neither conventional single-energy CT nor ICRU∕ICRP tissue composition compilations provide useful guidance for the task of assigning interaction cross sections to each voxel. (3) Since each patient-source-applicator combination is unique, having reference data for each possible combination to benchmark MBDCAs is an impractical strategy. Hence, a new commissioning process is required. TG-186 addresses in detail the above issues through the literature review and provides explicit recommendations based on the current state of knowledge. TG-43-based dose prescription and dose calculation remain in effect, with MBDCA dose reporting performed in parallel when available. In using MBDCAs, it is recommended that the radiation transport should be performed in the heterogeneous medium and, at minimum, the dose to the local medium be reported along with the TG-43 calculated doses. Assignments of voxel-by-voxel cross sections represent a particular challenge. Electron density information is readily extracted from CT imaging, but cannot be used to distinguish between different materials having the same density. Therefore, a recommendation is made to use a number of standardized materials to maintain uniformity across institutions. Sensitivity analysis shows that this recommendation offers increased accuracy over TG-43. MBDCA commissioning will share commonalities with current TG-43-based systems, but in addition there will be algorithm-specific tasks. Two levels of commissioning are recommended: reproducing TG-43 dose parameters and testing the advanced capabilities of MBDCAs. For validation of heterogeneity and scatter conditions, MBDCAs should mimic the 3D dose distributions from reference virtual geometries. Potential changes in BT dose prescriptions and MBDCA limitations are discussed. When data required for full MBDCA implementation are insufficient, interim recommendations are made and potential areas of research are identified. Application of TG-186 guidance should retain practice uniformity in transitioning from the TG-43 to the MBDCA approach.

Beyond the arcuate fasciculus: consensus and controversy in the connectional anatomy of language.

Abstract: The growing consensus that language is distributed into large-scale cortical and subcortical networks has brought with it an increasing focus on the connectional anatomy of language, or how particular fibre pathways connect regions within the language network. Understanding connectivity of the language network could provide critical insights into function, but recent investigations using a variety of methodologies in both humans and non-human primates have provided conflicting accounts of pathways central to language. Some of the pathways classically considered language pathways, such as the arcuate fasciculus, are now argued to be domain-general rather than specialized, which represents a radical shift in perspective. Other pathways described in the non-human primate remain to be verified in humans. In this review, we examine the consensus and controversy in the study of fibre pathway connectivity for language. We focus on seven fibre pathways-the superior longitudinal fasciculus and arcuate fasciculus, the uncinate fasciculus, extreme capsule, middle longitudinal fasciculus, inferior longitudinal fasciculus and inferior fronto-occipital fasciculus-that have been proposed to support language in the human. We examine the methods in humans and non-human primate used to investigate the connectivity of these pathways, the historical context leading to the most current understanding of their anatomy, and the functional and clinical correlates of each pathway with reference to language. We conclude with a challenge for researchers and clinicians to establish a coherent framework within which fibre pathway connectivity can be systematically incorporated to the study of language.

Distance without direction: Restoring credibility to a much-loved construct

Abstract: In this commentary we build on Shenkar's (2001) award-winning critique of cultural distance, arguing that most distance constructs, in fact, suffer the same flaws because they oversimplify the relationship between countries, overlook their subjective and context-specific nature, and pay insufficient attention to the mechanisms through which distance operates. The idea of distance, however, has intrinsic value. Moreover, its considerable appeal and undeniable effectiveness have made it a well-entrenched construct. Therefore we see merit in redressing its weaknesses, and offer several suggestions for doing so. These include allowing for the influence of firm-level characteristics that either moderate the effects of distance or render distance – at least in part – subjective with varying consequences for different MNEs; maintaining directionality by distinguishing between distance and the tendency toward a particular characteristic and acknowledging asymmetry; and conceptualizing the effects of distance and the mechanisms through which it operates more carefully by drawing on concepts and measures from a variety of disciplines. By offering ways to strengthen both its theoretical foundations and measurement, we hope to enhance the usefulness of one of international business theory's most central constructs.

Building Understanding of Smart City Initiatives

Abstract: This study presents the first results of an analysis primarily based on semi-structured interviews with government officials and managers who are responsible for smart city initiatives in four North American cities—Philadelphia and Seattle in the United States, Quebec City in Canada, and Mexico City in Mexico. With the reference to the Smart City Initiatives Framework that we suggested in our previous research, this study aims to build a new understanding of smart city initiatives. Main findings are categorized into eight aspects including technology, management and organization, policy context, governance, people and communities, economy, built infrastructure, and natural environment.

Cross-protective efficacy of two human papillomavirus vaccines: a systematic review and meta-analysis

Abstract: Summary Background The extent of cross-protection is a key element in the choice of human papillomavirus (HPV) vaccine to use in vaccination programmes. We compared the cross-protective efficacy of the bivalent vaccine (HPV 16 and 18; Cervarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) and quadrivalent vaccine (HPV 6, 11, 16, and 18; Gardasil, Merck, Whitehouse Station, NJ, USA) against non-vaccine type HPVs. Methods We searched Medline and Embase databases, conference abstracts, and manufacturers' websites for randomised clinical trials assessing the efficacy of bivalent and quadrivalent vaccines against persistent infections (lasting ≥6 months) and cervical intraepithelial neoplasia (CIN) associated with the non-vaccine type HPVs (types 31, 33, 45, 52, and 58). We included studies of participants who were HPV DNA negative before vaccination for all HPV types assessed. We assessed heterogeneity in vaccine efficacy estimates between trials with I 2 and χ 2 statistics. Findings We identified two clinical trials (Females United to Unilaterally Reduce Endo/Ectocervical Disease [FUTURE] I and II) of the quadrivalent vaccine and three (Papilloma Trial Against Cancer In Young Adults [PATRICIA], HPV007, and HPV-023) of the bivalent vaccine. Analysis of the most comparable populations (pooled FUTURE I/II data vs PATRICIA) suggested that cross-protective vaccine efficacy estimates against infections and lesions associated with HPV 31, 33, and 45 were usually higher for the bivalent vaccine than the quadrivalent vaccine. Vaccine efficacy in the bivalent trial was higher than it was in the quadrivalent trial against persistent infections with HPV 31 (77·1% [95% CI 67·2 to 84·4] for bivalent vaccine vs 46·2% [15·3 to 66·4] for quadrivalent vaccine; p=0·003) and HPV 45 (79·0% [61·3 to 89·4] vs 7·8% [–67·0 to 49·3]; p=0·0003), and against CIN grade 2 or worse associated with HPV 33 (82·3% [53·4 to 94·7] vs 24·0% [–71·2 to 67·2]; p=0·02) and HPV 45 (100% [41·7 to 100] vs −51·9% [–1717·8 to 82·6]; p=0·04). We noted substantial heterogeneity between vaccine efficacy in bivalent trials against persistent infections with HPV 31 ( I 2 =69%, p=0·04) and HPV 45 ( I 2 =70%, p=0·04), with apparent reductions in cross-protective efficacy with increased follow-up. Interpretation The bivalent vaccine seems more efficacious against non-vaccine HPV types 31, 33, and 45 than the quadrivalent vaccine, but the differences were not all significant and might be attributable to differences in trial design. Efficacy against persistent infections with types 31 and 45 seemed to decrease in bivalent trials with increased follow-up, suggesting a waning of cross-protection; more data are needed to establish duration of cross-protection. Funding Public Health Agency of Canada.

Organizational Citizenship Behaviour for the Environment: Measurement and Validation

Abstract: While the importance of employee initiatives for improving the environmental practices and performance of organizations has been clearly established in the literature, the precise nature of these initiatives has rarely been examined (particularly the issue of their discretionary or mandatory nature). The role of organizational citizenship behaviour in environmental management remains largely unexplored. The main objectives of this paper were to propose and validate an instrument for measuring organizational citizenship behaviour for the environment (OCBE). Exploratory (Study 1, N = 228) and confirmatory (Study 2, N = 651) analyses were conducted to examine the factor structure of OCBEs. The factor structure that emerged from Study 1 indicated that the three main types of OCBEs were eco-initiatives, eco-civic engagement and eco-helping. The factor structure found in Study 1 was confirmed by Study 2. Analysis of the three types of OCBEs highlighted the complexity of discretionary initiatives for the environment in the workplace and points to a number of avenues for further research.