Showing papers by "University of Calgary published in 2012"
TL;DR: Prevalence and severity of health loss were weakly correlated and age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010, but population growth and ageing have increased YLD numbers and crude rates over the past two decades.
7,021 citations
TL;DR: The results for 1990 and 2010 supersede all previously published Global Burden of Disease results and highlight the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account.
6,861 citations
TL;DR: Although there are few epidemiologic data from developing countries, the incidence and prevalence of IBD are increasing with time and in different regions around the world, indicating its emergence as a global disease.
4,096 citations
TL;DR: In this article, a variety of promising sorbents such as activated carbonaceous materials, microporous/mesoporous silica or zeolites, carbonates, and polymeric resins loaded with or without nitrogen functionality for the removal of CO2 from the flue gas streams have been reviewed.
Abstract: Post-combustion CO2 capture from the flue gas is one of the key technology options to reduce greenhouse gases, because this can be potentially retrofitted to the existing fleet of coal-fired power stations. Adsorption processes using solid sorbents capable of capturing CO2 from flue gas streams have shown many potential advantages, compared to other conventional CO2 capture using aqueous amine solvents. In view of this, in the past few years, several research groups have been involved in the development of new solid sorbents for CO2 capture from flue gas with superior performance and desired economics. A variety of promising sorbents such as activated carbonaceous materials, microporous/mesoporous silica or zeolites, carbonates, and polymeric resins loaded with or without nitrogen functionality for the removal of CO2 from the flue gas streams have been reviewed. Different methods of impregnating functional groups, including grafting techniques and modifying the support materials, have been discussed to en...
1,502 citations
TL;DR: It is suggested that some procedures potentially capable of generating aerosols have been associated with increased risk of SARS transmission to HCWs or were a risk factor for transmission, with the most consistent association across multiple studies identified with tracheal intubation.
Abstract: Aerosol generating procedures (AGPs) may expose health care workers (HCWs) to pathogens causing acute respiratory infections (ARIs), but the risk of transmission of ARIs from AGPs is not fully known. We sought to determine the clinical evidence for the risk of transmission of ARIs to HCWs caring for patients undergoing AGPs compared with the risk of transmission to HCWs caring for patients not undergoing AGPs. We searched PubMed, EMBASE, MEDLINE, CINAHL, the Cochrane Library, University of York CRD databases, EuroScan, LILACS, Indian Medlars, Index Medicus for SE Asia, international health technology agencies and the Internet in all languages for articles from 01/01/1990 to 22/10/2010. Independent reviewers screened abstracts using pre-defined criteria, obtained full-text articles, selected relevant studies, and abstracted data. Disagreements were resolved by consensus. The outcome of interest was risk of ARI transmission. The quality of evidence was rated using the GRADE system. We identified 5 case-control and 5 retrospective cohort studies which evaluated transmission of SARS to HCWs. Procedures reported to present an increased risk of transmission included [n; pooled OR(95%CI)] tracheal intubation [n = 4 cohort; 6.6 (2.3, 18.9), and n = 4 case-control; 6.6 (4.1, 10.6)], non-invasive ventilation [n = 2 cohort; OR 3.1(1.4, 6.8)], tracheotomy [n = 1 case-control; 4.2 (1.5, 11.5)] and manual ventilation before intubation [n = 1 cohort; OR 2.8 (1.3, 6.4)]. Other intubation associated procedures, endotracheal aspiration, suction of body fluids, bronchoscopy, nebulizer treatment, administration of O2, high flow O2, manipulation of O2 mask or BiPAP mask, defibrillation, chest compressions, insertion of nasogastric tube, and collection of sputum were not significant. Our findings suggest that some procedures potentially capable of generating aerosols have been associated with increased risk of SARS transmission to HCWs or were a risk factor for transmission, with the most consistent association across multiple studies identified with tracheal intubation.
1,469 citations
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24 May 2012TL;DR: Downregulation of intracortical inhibition induced by damage to the cochlea or to auditory projection pathways highlights neural processes that underlie the sensation of phantom sound.
Abstract: Tinnitus is an auditory phantom sensation (ringing of the ears) experienced when no external sound is present. Most but not all cases are associated with hearing loss induced by noise exposure or aging. Neuroscience research has begun to reveal how tinnitus is generated by the brain when hearing loss occurs, and to suggest new avenues for management and prevention of tinnitus following hearing injuries. Downregulation of intracortical inhibition induced by damage to the cochlea or to auditory projection pathways highlights neural processes that underlie the sensation of phantom sound.
1,109 citations
TL;DR: The assessment of its vasodilator properties resulting from NO and other molecules may provide information on the integrity and function of the endothelium, and most, if not all, cardiovascular risk factors are associated with endothelial dysfunction, and risk factor modification leads to improvement in vascular function.
Abstract: The discovery of nitric oxide (NO) as a crucial endothelium-derived molecule for vascular relaxation and the recognition of the endothelium as more than a passive interface between blood and the vessel wall led to substantial progress in the field of vascular research.1 Endothelial dysfunction is a pathological condition characterized mainly by an imbalance between substances with vasodilating, antimitogenic, and antithrombogenic properties (endothelium-derived relaxing factors)2 and substances with vasoconstricting, prothrombotic, and proliferative characteristics (endothelium-derived contracting factors).3 Among the most important vasodilator molecules, particularly in muscular arteries, is NO, which also inhibits other key events in the development of atherosclerosis such as platelet adhesion and aggregation, leukocyte adhesion and migration, and smooth muscle cell proliferation. Particularly in the microcirculation, prostacyclin and endothelium-derived hyperpolarization factors (an umbrella term for substances and signals hyperpolarizing vascular myocytes by opening voltage channels4) also play an important role.
Generally, loss of NO bioavailability indicates a broadly dysfunctional phenotype across many properties of the endothelium. Thus, the assessment of its vasodilator properties resulting from NO and other molecules may provide information on the integrity and function of the endothelium. Interestingly, most, if not all, cardiovascular risk factors are associated with endothelial dysfunction,5 and risk factor modification leads to improvement in vascular function. Endothelial dysfunction has been detected in the coronary epicardial and resistance vasculature and in peripheral arteries, so endothelial dysfunction can be regarded as a systemic condition.6 Importantly, the process of atherosclerosis begins early in life, and endothelial dysfunction contributes to atherogenesis and precedes the development of morphological vascular changes.7
Over the past 25 years, many methodological approaches have been developed to measure the (patho)physiological function of the endothelium in humans.8 Although the ability to measure endothelial function has boosted clinical research in this field, its use as a …
964 citations
William F. Laurance1, William F. Laurance2, D. Carolina Useche2, Julio Rendeiro2 +213 more•Institutions (101)
TL;DR: These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.
Abstract: The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon(1-3). With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses(4-9). As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world's major tropical regions. Our analysis reveals great variation in reserve 'health': about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.
962 citations
TL;DR: Based on the current clinical trials, MSC therapy appears safe, however, further larger scale controlled clinical trials with rigorous reporting of adverse events are required to further define the safety profile of MSCs.
Abstract: Background Mesenchymal stromal cells (MSCs, “adult stem cells”) have been widely used experimentally in a variety of clinical contexts. There is interest in using these cells in critical illness, however, the safety profile of these cells is not well known. We thus conducted a systematic review of clinical trials that examined the use MSCs to evaluate their safety. Methods and Findings MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (to June 2011), were searched. Prospective clinical trials that used intravascular delivery of MSCs (intravenously or intra-arterially) in adult populations or mixed adult and pediatric populations were identified. Studies using differentiated MSCs or additional cell types were excluded. The primary outcome adverse events were grouped according to immediate events (acute infusional toxicity, fever), organ system complications, infection, and longer term adverse events (death, malignancy). 2347 citations were reviewed and 36 studies met inclusion criteria. A total of 1012 participants with clinical conditions of ischemic stroke, Crohn's disease, cardiomyopathy, myocardial infarction, graft versus host disease, and healthy volunteers were included. Eight studies were randomized control trials (RCTs) and enrolled 321 participants. Meta-analysis of the RCTs did not detect an association between acute infusional toxicity, organ system complications, infection, death or malignancy. There was a significant association between MSCs and transient fever. Conclusions Based on the current clinical trials, MSC therapy appears safe. However, further larger scale controlled clinical trials with rigorous reporting of adverse events are required to further define the safety profile of MSCs.
940 citations
University of California, San Diego1, Janssen Pharmaceutica2, Icahn School of Medicine at Mount Sinai3, University of Chicago4, Cedars-Sinai Medical Center5, Katholieke Universiteit Leuven6, University of Calgary7, University of Kentucky8, University of Toronto9, University of Kiel10, University of Western Ontario11
TL;DR: Patients with moderate-to-severe Crohn's disease that was resistant to TNF antagonists had an increased rate of response to induction with ustekinumab, as compared with placebo.
Abstract: Background In patients with Crohn's disease, the efficacy of ustekinumab, a human monoclonal antibody against interleukin-12 and interleukin-23, is unknown. Methods We evaluated ustekinumab in adul...
934 citations
TL;DR: In this article, the essence of family influence partially mediates the relationship between family involvement and family firms' adoption of family-centered noneconomic goals, and the results using 1,060 small firms support the hypotheses.
Abstract: Using behavioral and stakeholder theories, we suggest that family firms may have family-centered non-economic goals and that these goals could influence firm behaviors. This study extends the literature by hypothesizing that the essence of family influence partially mediates the relationship between family involvement and family firms' adoption of family-centered non-economic goals. The results using 1,060 small firms support the hypotheses. Aside from contributing to family business theory by explaining and testing mediating variables as sources of goal heterogeneity among family firms, our findings also imply that the involvement and essence approaches to defining family businesses may be hierarchically reconciled.
Johns Hopkins University1, University of Groningen2, University of Oxford3, Aga Khan University4, Yonsei University5, University of West Virginia6, Kaiser Permanente7, University of Alberta8, University of Alabama at Birmingham9, National Health Research Institutes10, China Medical University (Taiwan)11, University of Calgary12, Tufts Medical Center13
TL;DR: The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.
Abstract: 2) was reducedfrom8.7%to6.3%.InestimatedGFRof45to59mL/min/1.73m 2 bytheMDRD Study equation, 34.7% of participants were reclassified to estimated GFR of 60 to 89 mL/min/1.73m 2 bytheCKD-EPIequationandhadlowerincidencerates(per1000personyears) for the outcomes of interest (9.9 vs 34.5 for all-cause mortality, 2.7 vs 13.0 for cardiovascular mortality, and 0.5 vs 0.8 for ESRD) compared with those not reclassified. The corresponding adjusted hazard ratios were 0.80 (95% CI, 0.74-0.86) for all-cause mortality, 0.73 (95% CI, 0.65-0.82) for cardiovascular mortality, and 0.49 (95% CI, 0.270.88) for ESRD. Similar findings were observed in other estimated GFR categories by the MDRD Study equation. Net reclassification improvement based on estimated GFR categories was significantly positive for all outcomes (range, 0.06-0.13; all P.001). Net reclassificationimprovementwassimilarlypositiveinmostsubgroupsdefinedbyage(65 years and 65 years), sex, race/ethnicity (white, Asian, and black), and presence or absence of diabetes and hypertension. The results in the high-risk and CKD cohorts were largely consistent with the general population cohorts. Conclusion The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.
TL;DR: Gallstone disease in childhood, once considered rare, has become increasingly recognized with similar risk factors as those in adults, particularly obesity.
Abstract: Diseases of the gallbladder are common and costly. The best epidemiological screening method to accurately determine point prevalence of gallstone disease is ultrasonography. Many risk factors for cholesterol gallstone formation are not modifiable such as ethnic background, increasing age, female gender and family history or genetics. Conversely, the modifiable risks for cholesterol gallstones are obesity, rapid weight loss and a sedentary lifestyle. The rising epidemic of obesity and the metabolic syndrome predicts an escalation of cholesterol gallstone frequency. Risk factors for biliary sludge include pregnancy, drugs like ceftiaxone, octreotide and thiazide diuretics, and total parenteral nutrition or fasting. Diseases like cirrhosis, chronic hemolysis and ileal Crohn's disease are risk factors for black pigment stones. Gallstone disease in childhood, once considered rare, has become increasingly recognized with similar risk factors as those in adults, particularly obesity. Gallbladder cancer is uncommon in developed countries. In the U.S., it accounts for only ~ 5,000 cases per year. Elsewhere, high incidence rates occur in North and South American Indians. Other than ethnicity and female gender, additional risk factors for gallbladder cancer include cholelithiasis, advancing age, chronic inflammatory conditions affecting the gallbladder, congenital biliary abnormalities, and diagnostic confusion over gallbladder polyps.
TL;DR: Early in infection NETosis involves neutrophils that do not undergo lysis and retain the ability to multitask, and a requirement for both Toll-like receptor 2 and complement-mediated opsonization tightly regulated NET release.
Abstract: Neutrophil extracellular traps (NETs) are released as neutrophils die in vitro in a process requiring hours, leaving a temporal gap that invasive microbes may exploit. Neutrophils capable of migration and phagocytosis while undergoing NETosis have not been documented. During Gram-positive skin infections, we directly visualized live polymorphonuclear cells (PMNs) in vivo rapidly releasing NETs, which prevented systemic bacterial dissemination. NETosis occurred during crawling, thereby casting large areas of NETs. NET-releasing PMNs developed diffuse decondensed nuclei, ultimately becoming devoid of DNA. Cells with abnormal nuclei showed unusual crawling behavior highlighted by erratic pseudopods and hyperpolarization consistent with the nucleus being a fulcrum for crawling. A requirement for both Toll-like receptor 2 and complement-mediated opsonization tightly regulated NET release. Additionally, live human PMNs injected into mouse skin developed decondensed nuclei and formed NETS in vivo, and intact anuclear neutrophils were abundant in Gram-positive human abscesses. Therefore early in infection NETosis involves neutrophils that do not undergo lysis and retain the ability to multitask.
TL;DR: In this paper, the authors developed a 24-item memorable tourism experience scale that comprises seven domains: hedonism, refreshment, local culture, meaningfulness, knowledge, involvement, and novelty.
Abstract: The quality experiences provided to customers, which are indeed memorable, directly determine a business’s ability to generate revenue (Pine and Gilmore 1999). However, the extant tourism literature has provided limited explanation of the factors that characterize memorable tourism experiences. Thus, the goal of the present study was to develop a valid and reliable measurement scale that will assist in understanding the concept and in improving the effective management of the memorable experience. Following Churchill’s (1979) recommended process, we developed a 24-item memorable tourism experience scale that we believe is applicable to most destination areas. The scale comprises seven domains: hedonism, refreshment, local culture, meaningfulness, knowledge, involvement, and novelty. The data support this dimensional structure of the memorable tourism experience as well as its internal consistency and validity (i.e., content, construct, convergent, and discriminant validity). Theoretical and managerial imp...
University of Toronto1, German Cancer Research Center2, Harvard University3, Broad Institute4, University of British Columbia5, Heidelberg University6, Memorial Sloan Kettering Cancer Center7, Vanderbilt University8, Sanford-Burnham Institute for Medical Research9, Medical University of Vienna10, Curie Institute11, University of Lausanne12, Seoul National University13, Johns Hopkins University14, University of Lyon15, University of Pittsburgh16, University of Michigan17, University of Alabama at Birmingham18, Catholic University of the Sacred Heart19, Erasmus University Rotterdam20, Boston Children's Hospital21, University of Washington22, Masaryk University23, Hamilton Health Sciences24, McMaster University25, Duke University26, McGill University27, McGill University Health Centre28, Newcastle University29, University of California, San Francisco30, University of Debrecen31, Tohoku University32, Saint Louis University33, Washington University in St. Louis34, University of California, Los Angeles35, Emory University36, University of Cincinnati37, Kumamoto University38, Semmelweis University39, University of Arkansas for Medical Sciences40, University of Naples Federico II41, Chonnam National University42, University of São Paulo43, University of Colorado Denver44, University of Ulsan45, University of Calgary46, Stanford University47
TL;DR: Somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas are reported, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Groups 4, which suggest future avenues for rational, targeted therapy.
Abstract: Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy.
Utrecht University1, University of Calgary2, University College London3, VU University Amsterdam4, Lund University5, Wake Forest University6, Radboud University Nijmegen7, University of Malaya8, Erasmus University Rotterdam9, Osaka University10, McMaster University11, Goethe University Frankfurt12, University of Tromsø13, Tufts University14, University of Edinburgh15, University of Virginia16, University of Miami17, Analytical Services18, Maastricht University19
TL;DR: The addition of common CIMT measurements to the Framingham Risk Score was associated with small improvement in 10-year risk prediction of first-time myocardial infarction or stroke, but this improvement is unlikely to be of clinical importance.
Abstract: Context: The evidence that measurement of the common carotid intima-media thickness (CIMT) improves the risk scores in prediction of the absolute risk of cardiovascular events is inconsistent. Objective: To determine whether common CIMT has added value in 10-year risk prediction of first-time myocardial infarctions or strokes, above that of the Framingham Risk Score. Data Sources: Relevant studies were identified through literature searches of databases (PubMed from 1950 to June 2012 and EMBASE from 1980 to June 2012) and expert opinion. Study Selection: Studies were included if participants were drawn from the general population, common CIMT was measured at baseline, and individuals were followed up for first-time myocardial infarction or stroke. Data Extraction: Individual data were combined into 1 data set and an individual participant data meta-analysis was performed on individuals without existing cardiovascular disease. Results: We included 14 population-based cohorts contributing data for 45 828 individuals. During a median follow-up of 11 years, 4007 first-time myocardial infarctions or strokes occurred. We first refitted the risk factors of the Framingham Risk Score and then extended the model with common CIMT measurements to estimate the absolute 10-year risks to develop a first-time myocardial infarction or stroke in both models. The C statistic of both models was similar (0.757; 95% CI, 0.749-0.764; and 0.759; 95% CI, 0.752-0.766). The net reclassification improvement with the addition of common CIMT was small (0.8%; 95% CI, 0.1%-1.6%). In those at intermediate risk, the net reclassification improvement was 3.6% in all individuals (95% CI, 2.7%-4.6%) and no differences between men and women. Conclusion: The addition of common CIMT measurements to the Framingham Risk Score was associated with small improvement in 10-year risk prediction of first-time myocardial infarction or stroke, but this improvement is unlikely to be of clinical importance.
TL;DR: Findings define an enantiomer-specific mechanism by which the (R)-2HG that accumulates in IDH mutant brain tumours promotes transformation and provide a justification for exploring EGLN inhibition as a potential treatment strategy.
Abstract: The identification of succinate dehydrogenase (SDH), fumarate hydratase (FH) and isocitrate dehydrogenase (IDH) mutations in human cancers has rekindled the idea that altered cellular metabolism can transform cells. Inactivating SDH and FH mutations cause the accumulation of succinate and fumarate, respectively, which can inhibit 2-oxoglutarate (2-OG)-dependent enzymes, including the EGLN prolyl 4-hydroxylases that mark the hypoxia inducible factor (HIF) transcription factor for polyubiquitylation and proteasomal degradation. Inappropriate HIF activation is suspected of contributing to the pathogenesis of SDH-defective and FH-defective tumours but can suppress tumour growth in some other contexts. IDH1 and IDH2, which catalyse the interconversion of isocitrate and 2-OG, are frequently mutated in human brain tumours and leukaemias. The resulting mutants have the neomorphic ability to convert 2-OG to the (R)-enantiomer of 2-hydroxyglutarate ((R)-2HG). Here we show that (R)-2HG, but not (S)-2HG, stimulates EGLN activity, leading to diminished HIF levels, which enhances the proliferation and soft agar growth of human astrocytes. These findings define an enantiomer-specific mechanism by which the (R)-2HG that accumulates in IDH mutant brain tumours promotes transformation and provide a justification for exploring EGLN inhibition as a potential treatment strategy.
TL;DR: The International Society for Quality of Life Research (ISOQOL) has developed a User's Guide for Implementing Patient-Reported Outcomes Assessment in Clinical Practice as mentioned in this paper, which outlines considerations for using PROs in clinical practice; options for designing the intervention; and strengths, weaknesses, and resource requirements associated with each option.
Abstract: While clinical care is frequently directed at making patients “feel better,” patients’ reports on their functioning and well-being (patient-reported outcomes [PROs]) are rarely collected in routine clinical practice. The International Society for Quality of Life Research (ISOQOL) has developed a User’s Guide for Implementing Patient-Reported Outcomes Assessment in Clinical Practice. This paper summarizes the key issues from the User’s Guide. Using the literature, an ISOQOL team outlined considerations for using PROs in clinical practice; options for designing the intervention; and strengths, weaknesses, and resource requirements associated with each option. Implementing routine PRO assessment involves a number of methodological and practical decisions, including (1) identifying the goals for collecting PROs in clinical practice, (2) selecting the patients, setting, and timing of assessments, (3) determining which questionnaire(s) to use, (4) choosing a mode for administering and scoring the questionnaire, (5) designing processes for reporting results, (6) identifying aids to facilitate score interpretation, (7) developing strategies for responding to issues identified by the questionnaires, and (8) evaluating the impact of the PRO intervention on the practice. Integrating PROs in clinical practice has the potential to enhance patient-centered care. The online version of the User’s Guide will be updated periodically.
TL;DR: It is shown that neutrophils migrate to liver sinusoids during endotoxemia and sepsis where they exert protective effects by releasing neutrophil extracellular traps, which are DNA-based structures that capture and eliminate microbes.
TL;DR: Sarcopenia predicts postoperative infections, inpatient rehabilitation care and consequently a longer length of stay (LOS) in stage II–IV patients.
Abstract: Sarcopenia is associated with postoperative infection and delayed recovery from colorectal cancer resection surgery
TL;DR: This paper updates the literature review on MC presented in a previous paper, and identifies research gaps to be investigated in the future through summary statistics.
TL;DR: The findings suggest that chronic kidney disease could be added to the list of criteria defining people at highest risk of future coronary events.
Boston Children's Hospital1, University of Chicago2, University of Washington3, University of Sussex4, Michigan State University5, McGill University6, Alfred I. duPont Hospital for Children7, Cedars-Sinai Medical Center8, University of Duisburg-Essen9, Queen's University10, University of British Columbia11, University of Calgary12, University of Toronto13, Medical College of Wisconsin14, Harvard University15, Erasmus University Rotterdam16, Providence Sacred Heart Medical Center and Children's Hospital17, St George’s University Hospitals NHS Foundation Trust18, Wolfson Medical Center19, University of Hamburg20, University of Göttingen21, University of Ottawa22
TL;DR: Exome sequencing identified de novo germline or postzygotic mutations in three core components of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, highlighting the central role of PI3K-AKT signaling in vascular, limb and brain development.
Abstract: Megalencephaly-capillary malformation (MCAP) and megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndromes are sporadic overgrowth disorders associated with markedly enlarged brain size and other recognizable features. We performed exome sequencing in 3 families with MCAP or MPPH, and our initial observations were confirmed in exomes from 7 individuals with MCAP and 174 control individuals, as well as in 40 additional subjects with megalencephaly, using a combination of Sanger sequencing, restriction enzyme assays and targeted deep sequencing. We identified de novo germline or postzygotic mutations in three core components of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. These include 2 mutations in AKT3, 1 recurrent mutation in PIK3R2 in 11 unrelated families with MPPH and 15 mostly postzygotic mutations in PIK3CA in 23 individuals with MCAP and 1 with MPPH. Our data highlight the central role of PI3K-AKT signaling in vascular, limb and brain development and emphasize the power of massively parallel sequencing in a challenging context of phenotypic and genetic heterogeneity combined with postzygotic mosaicism.
TL;DR: It is hypothesized that socioemotional wealth increases with the extent of current control, duration of control, and intentions for transgenerational control, thus adding to the price at which owners would be willing to sell their firms to nonfamily buyers.
Abstract: Family firms are thought to pursue nonfinancial goals that provide socioemotional wealth, but socioemotional wealth is feasible only with family control of the firm. Using prospect theory, we hypothesize that socioemotional wealth increases with the extent of current control, duration of control, and intentions for transgenerational control, thus adding to the price at which owners would be willing to sell their firms to nonfamily buyers. Findings from two countries show that current control has no impact, and duration of control has a mixed impact. However, intention for transgenerational control has a consistently positive impact on the perceived acceptable selling price.
Rutgers University1, University of California, San Francisco2, University of Texas MD Anderson Cancer Center3, Washington University in St. Louis4, University of Chicago5, Emory University6, Princess Margaret Cancer Centre7, University of Calgary8, University of South Florida9, Mayo Clinic10, Cleveland Clinic11, City of Hope National Medical Center12, Wayne State University13, University of British Columbia14, University of Pennsylvania15, Onyx Pharmaceuticals16, Icahn School of Medicine at Mount Sinai17
TL;DR: Durable responses and an acceptable tolerability profile in this heavily pretreated population demonstrate the potential of carfilzomib to offer meaningful clinical benefit.
University of Alabama1, California State University, Bakersfield2, Field Museum of Natural History3, University of Bristol4, University of Texas at Austin5, University of Chicago6, University of Nebraska–Lincoln7, University of California, Berkeley8, University of Tokyo9, American Museum of Natural History10, University of Tübingen11, North Carolina Museum of Natural Sciences12, North Carolina State University13, Instituto Butantan14, Dartmouth College15, University of North Carolina at Wilmington16, University College London17, Humboldt University of Berlin18, University of California, Santa Cruz19, Southern Methodist University20, University of Calgary21
TL;DR: A specimen-based protocol for selecting and documenting relevant fossils is presented and future directions for evaluating and utilizing phylogenetic and temporal data from the fossil record are discussed, to establish the best practices for justifying fossils used for the temporal calibration of molecular phylogenies.
Abstract: At this time, no abstract is available. SciVerse Scopus has content delivery agreements in place with each publisher and currently contains 30 million records with an abstract. An abstract may not be present due to incomplete data, as supplied by the publisher, or is still in the process of being indexed.
TL;DR: The effectiveness of QI strategies varied depending on baseline HbA(1c) control, and interventions targeting the system of chronic disease management along with patient-mediatedQI strategies should be an important component of interventions aimed at improving diabetes management.
TL;DR: The current practices in the information visualization research community are encapsulated and a different approach is provided to reaching decisions about what might be the most effective evaluation of a given information visualization.
Abstract: We take a new, scenario-based look at evaluation in information visualization. Our seven scenarios, evaluating visual data analysis and reasoning, evaluating user performance, evaluating user experience, evaluating environments and work practices, evaluating communication through visualization, evaluating visualization algorithms, and evaluating collaborative data analysis were derived through an extensive literature review of over 800 visualization publications. These scenarios distinguish different study goals and types of research questions and are illustrated through example studies. Through this broad survey and the distillation of these scenarios, we make two contributions. One, we encapsulate the current practices in the information visualization research community and, two, we provide a different approach to reaching decisions about what might be the most effective evaluation of a given information visualization. Scenarios can be used to choose appropriate research questions and goals and the provided examples can be consulted for guidance on how to design one's own study.
TL;DR: In this paper, the authors examine how vision and goals, as well as the discretion engendered by family control, influence the innovation, internationalization, succession, professionalization, and proactive stakeholder engagement of family enterprises.
Abstract: Family business researchers have devoted substantial attention to comparing family firms with nonfamily firms. Many of these comparisons rely on dichotomous variables, which implicitly treat family firms as homogeneous entities. However, recent studies have started to use moderators and mediators as well as continuous measures of family involvement in recognition of the heterogeneity of family firms. The articles and commentaries in this special issue contribute to a better understanding of that heterogeneity by examining how vision and goals, as well as the discretion engendered by family control, influence the innovation, internationalization, succession, professionalization, and proactive stakeholder engagement of family enterprises.