Showing papers by "University of Miami published in 2011"
National Institutes of Health1, Cardiff University2, Erasmus University Rotterdam3, VU University Amsterdam4, University of Manchester5, University College London6, University of Helsinki7, University of Oulu8, Georgetown University9, Johns Hopkins University10, Illumina11, University Hospital of Wales12, University of Eastern Finland13, University of Miami14, University of Turin15, University of Cagliari16, The Catholic University of America17, Microsoft18, University of Toronto19, University of Würzburg20, University of Washington21, Aneurin Bevan University Health Board22
TL;DR: The chromosome 9p21 amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) locus contains one of the last major unidentified autosomal-dominant genes underlying these common neurodegenerative diseases, and a large hexanucleotide repeat expansion in the first intron of C9ORF72 is shown.
3,784 citations
Stephen Sawcer1, Garrett Hellenthal2, Matti Pirinen2, Chris C. A. Spencer2 +262 more•Institutions (67)
TL;DR: In this article, a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, they have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci.
Abstract: Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
2,511 citations
TL;DR: Treatment of women with acute uncomplicated cystitis and pyelonephritis is limited in these guidelines to premenopausal, non-pregnant women with no known urological abnormalities or co-morbidities.
Abstract: A Panel of International Experts was convened by the Infectious Diseases Society of America (IDSA) in collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) to update the 1999 Uncomplicated Urinary Tract Infection Guidelines by the IDSA. Co-sponsoring organizations include the American Congress of Obstetricians and Gynecologists, American Urological Association, Association of Medical Microbiology and Infectious Diseases-Canada, and the Society for Academic Emergency Medicine. The focus of this work is treatment of women with acute uncomplicated cystitis and pyelonephritis, diagnoses limited in these guidelines to premenopausal, non-pregnant women with no known urological abnormalities or co-morbidities. The issues of in vitro resistance prevalence and the ecological adverse effects of antimicrobial therapy (collateral damage) were considered as important factors in making optimal treatment choices and thus are reflected in the rankings of recommendations.
2,320 citations
TL;DR: The Alzheimer Disease Genetics Consortium performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1), two replication stages (stages 2 and 3), and both joint analysis and meta-analysis approaches were used.
Abstract: The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.
1,743 citations
University of Miami1, University of Texas Southwestern Medical Center2, University of Alabama at Birmingham3, Harvard University4, Veterans Health Administration5, University of Illinois at Chicago6, Wake Forest University7, Tulane University8, University of California, San Francisco9, University of Pennsylvania10, University of Michigan11, Temple University12, University of Münster13, National Institutes of Health14
TL;DR: It is reported that elevated FGF23 levels are independently associated with LVH in a large, racially diverse CKD cohort and suggested that chronically elevated F GF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD.
Abstract: Chronic kidney disease (CKD) is a public health epidemic that increases risk of death due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiovascular disease in individuals with CKD. Elevated levels of FGF23 have been linked to greater risks of LVH and mortality in patients with CKD, but whether these risks represent causal effects of FGF23 is unknown. Here, we report that elevated FGF23 levels are independently associated with LVH in a large, racially diverse CKD cohort. FGF23 caused pathological hypertrophy of isolated rat cardiomyocytes via FGF receptor–dependent activation of the calcineurin-NFAT signaling pathway, but this effect was independent of klotho, the coreceptor for FGF23 in the kidney and parathyroid glands. Intramyocardial or intravenous injection of FGF23 in wild-type mice resulted in LVH, and klotho-deficient mice demonstrated elevated FGF23 levels and LVH. In an established animal model of CKD, treatment with an FGF–receptor blocker attenuated LVH, although no change in blood pressure was observed. These results unveil a klotho-independent, causal role for FGF23 in the pathogenesis of LVH and suggest that chronically elevated FGF23 levels contribute directly to high rates of LVH and mortality in individuals with CKD.
1,709 citations
TL;DR: In this article, the CAPACITY program was designed to confirm the results of a phase 2 study that suggested that pirfenidone, a novel antifibrotic and anti-inflammatory drug, reduces deterioration in lung function in patients with idiopathic pulmonary fibrosis.
1,685 citations
TL;DR: Narrow bandgap conjugated polymers in combination with fullerene acceptors, as well as the values used for the absolute potentials of standard electrodes, can complicate the comparison of materials properties and determination of structure/property relationships.
Abstract: Narrow bandgap conjugated polymers in combination with fullerene acceptors are under intense investigation in the field of organic photovoltaics (OPVs). The open circuit voltage, and thereby the power conversion efficiency, of the devices is related to the offset of the frontier orbital energy levels of the donor and acceptor components, which are widely determined by cyclic voltammetry. Inconsistencies have appeared in the use of the ferrocenium/ferrocene (Fc + /Fc) redox couple, as well as the values used for the absolute potentials of standard electrodes, which can complicate the comparison of materials properties and determination of structure/property relationships.
1,681 citations
TL;DR: Although the number of reports analyzed in this meta-analysis is small, these results show that SBME with DP is superior to traditional clinical medical education in achieving specific clinical skill acquisition goals.
Abstract: Purpose This article presents a comparison of the effectiveness of traditional clinical education toward skill acquisition goals versus simulation-based medical education (SBME) with deliberate practice (DP). Method This is a quantitative meta-analysis that spans 20 years, 1990 to 2010. A search strategy involving three literature databases, 12 search terms, and four inclusion criteria was used. Four authors independently retrieved and reviewed articles. Main outcome measures were extracted to calculate effect sizes.
1,311 citations
Mayo Clinic1, New York University2, University of Hamburg3, Children's National Medical Center4, University of Girona5, Johns Hopkins University6, St George's, University of London7, Harvard University8, University of Ottawa9, University of Toronto10, University of Miami11, University of Paris12, University College London13, University of Münster14, University of Sydney15, Cincinnati Children's Hospital Medical Center16, University of Oxford17, University of Amsterdam18, Indiana University19
TL;DR: This dissertation aims to provide a history of modern medicine and some of the techniques and practices used in modern medicine, as well as some new approaches, that were introduced in the field of medicine more than 40 years ago.
1,254 citations
University of California, Davis1, University of Massachusetts Boston2, University of Miami3, Hebrew University of Jerusalem4, University of Alberta5, Dalhousie University6, University of California, San Diego7, Washington University in St. Louis8, University of California, Los Angeles9, University of Pittsburgh10, Kennedy Krieger Institute11, University of Washington12
TL;DR: The sibling recurrence rate of ASD is higher than suggested by previous estimates, and the size of the current sample and prospective nature of data collection minimized many limitations of previous studies ofibling recurrence.
Abstract: The recurrence risk of autism spectrum disorders (ASD) is estimated to be between 3% and 10%, but previous research was limited by small sample sizes and biases related to ascertainment, reporting, and stoppage factors. This study used prospective methods to obtain an updated estimate of sibling recurrence risk for ASD. METHODS: A prospective longitudinal study of infants at risk for ASD was conducted by a multisite international network, the Baby Siblings Research Consortium. Infants (n 664) with an older biological sibling with ASD were followed from early in life to 36 months, when they were classified as having or not having ASD. An ASD classification required surpassing the cutoff of the Autism Diagnostic Observation Schedule and receiving a clinical diagnosis from an expert clinician. RESULTS: A total of 18.7% of the infants developed ASD. Infant gender and the presence of 1 older affected sibling were significant predic- tors of ASD outcome, and there was an almost threefold increase in risk for male subjects and an additional twofold increase in risk if there was 1 older affected sibling. The age of the infant at study enrollment, the gender and functioning level of the infant's older sib- ling, and other demographic factors did not predict ASD outcome. CONCLUSIONS: The sibling recurrence rate of ASD is higher than sug- gested by previous estimates. The size of the current sample and pro- spective nature of data collection minimized many limitations of previ- ous studies of sibling recurrence. Clinical implications, including genetic counseling, are discussed. Pediatrics 2011;128:e000
1,225 citations
Mayo Clinic1, New York University2, University of Hamburg3, George Washington University4, University of Girona5, Johns Hopkins University6, St George's, University of London7, Harvard University8, University of Ottawa9, Hospital for Sick Children10, University of Miami11, Paris Descartes University12, University College London13, University of Sydney14, Cincinnati Children's Hospital Medical Center15, John Radcliffe Hospital16, University of Amsterdam17, Indiana University18
TL;DR: This international consensus statement provides the state of genetic testing for the channelopathy and cardiomyopathies and summarizes the opinion of the international writing group members based on their own experience and on a general review of the literature with respect to the use and role of geneticTesting for these potentially heritable cardiac conditions.
Abstract: This international consensus statement provides the state of genetic testing for the channelopathies and cardiomyopathies. It summarizes the opinion of the international writing group members based on their own experience and on a general review of the literature with respect to the use and role of genetic testing for these potentially heritable cardiac conditions. This document focuses primarily on the state of genetic testing for the 13 distinct entities detailed and the relative diagnostic, prognostic, and therapeutic impact of the genetic test result for each entity. It does not focus on the therapeutic management of the various channelopathies and cardiomyopathies. Treatment/management issues are only discussed for those diseases (i.e., LQTS, HCM, DCM + CCD, RCM) in which the genetic test result could potentially influence treatment considerations.
Writing recommendations for genetic diseases require adaptation of the methodology normally adopted to prepare guidelines for clinical practice. Documents produced by other scientific societies have acknowledged the need to define the criteria used to rank the strength of recommendation for genetic diseases.1
The most obvious difference is that randomized and/or blinded studies do not exist. Instead, most of the available data are derived from registries that have followed patients and recorded outcome information. The authors of this statement have therefore defined specific criteria for Class I, Class IIa or b, and Class III recommendations and have used the conventional language adopted by AHA/ACC/ESC Guidelines to express each class. All recommendations are level of evidence (LOE) C (i.e., based on experts' opinions).
A Class I recommendation ( “is recommended” ) was applied for genetic testing in index cases with a sound clinical suspicion for the presence of a channelopathy or a cardiomyopathy when the positive predictive value of a genetic test is high (likelihood of positive result >40% and signal/noise ratio >10; Table 3), AND/OR when …
TL;DR: Findings link abnormalities in ubiquilin 2 to defects in the protein degradation pathway, abnormal protein aggregation and neurodegeneration, indicating a common pathogenic mechanism that can be exploited for therapeutic intervention.
Abstract: ing cases of familial ALS and of the vast majority of sporadic ALS are unknown. Despite extensive studies of previously identified ALS-causing genes, the pathogenic mechanism underlying motorneuron degeneration in ALS remains largely obscure. Dementia, usually of the frontotemporal lobar type, may occur in some ALS cases. It is unclear whether ALS and dementia share common aetiology and pathogenesis in ALS/dementia. Here we show that mutations in UBQLN2, which encodes the ubiquitin-like protein ubiquilin 2, cause dominantly inherited, chromosome-X-linked ALS and ALS/dementia. We describe novel ubiquilin 2 pathology in the spinal cords of ALS cases and in the brains of ALS/dementia cases with or without UBQLN2 mutations. Ubiquilin 2 is a member of the ubiquilin family, which regulates the degradation of ubiquitinated proteins. Functional analysis showed that mutations in UBQLN2 lead to an impairment of protein degradation. Therefore, our findings link abnormalities in ubiquilin 2 to defects in the protein degradation pathway, abnormal protein aggregation and neurodegeneration, indicating a common pathogenic mechanism that can be exploited for therapeutic intervention.
TL;DR: Increased FGF23 is a common manifestation of CKD that develops earlier than increased phosphate or PTH, and may be a sensitive early biomarker of disordered phosphorus metabolism in patients with CKD and normal serum phosphate levels.
TL;DR: The findings suggest that dysregulated MUC5B expression in the lung may be involved in the pathogenesis of pulmonary fibrosis, and a common polymorphism in the promoter of M UC5B is associated with familial interstitial pneumonia and idiopathic pulmonary fibrot.
Abstract: A b s t r ac t Background The mutations that have been implicated in pulmonary fibrosis account for only a small proportion of the population risk Methods Using a genomewide linkage scan, we detected linkage between idiopathic interstitial pneumonia and a 34-Mb region of chromosome 11p15 in 82 families We then evaluated genetic variation in this region in gel-forming mucin genes expressed in the lung among 83 subjects with familial interstitial pneumonia, 492 subjects with idiopathic pulmonary fibrosis, and 322 controls MUC5B expression was assessed in lung tissue Results Linkage and fine mapping were used to identify a region of interest on the p-terminus of chromosome 11 that included gel-forming mucin genes The minor-allele of the single-nucleotide polymorphism (SNP) rs35705950, located 3 kb upstream of the MUC5B transcription start site, was present at a frequency of 34% among subjects with familial interstitial pneumonia, 38% among subjects with idiopathic pulmonary fibrosis, and 9% among controls (allelic association with familial interstitial pneumonia, P = 12×10 − 15 ; allelic association with idiopathic pulmonary fibrosis, P = 25×10 − 37 ) The odds ratios for disease among subjects who were heterozygous and those who were homozygous for the minor allele of this SNP were 68 (95% confidence interval [CI], 39 to 120) and 208 (95% CI, 38 to 1137), respectively, for familial interstitial pneumonia and 90 (95% CI, 62 to 131) and 218 (95% CI, 51 to 935), respectively, for idiopathic pulmonary fibrosis MUC5B expression in the lung was 141 times as high in subjects who had idiopathic pulmonary fibrosis as in those who did not (P<0001) The variant allele of rs35705950 was associated with up-regulation in MUC5B expression in the lung in unaffected subjects (expression was 374 times as high as in unaffected subjects homozygous for the wild-type allele, P<0001) MUC5B protein was expressed in lesions of idiopathic pulmonary fibrosis Conclusions A common polymorphism in the promoter of MUC5B is associated with familial interstitial pneumonia and idiopathic pulmonary fibrosis Our findings suggest that dysregulated MUC5B expression in the lung may be involved in the pathogenesis of pulmonary fibrosis (Funded by the National Heart, Lung, and Blood Institute and others)
TL;DR: In this paper, the authors analyze the emerging crowd-funding phenomenon, that is a collective effort by consumers who network and pool their money together, usually via the internet, to invest in and support efforts initiated by other people or organizations.
Abstract: Purpose – The purpose of this paper is to analyze the emerging crowd‐funding phenomenon, that is a collective effort by consumers who network and pool their money together, usually via the internet, in order to invest in and support efforts initiated by other people or organizations. Successful service businesses that organize crowd‐funding and act as intermediaries are emerging, attesting to the viability of this means of attracting investment.Design/methodology/approach – The research employs a “grounded theory” approach, performing an in‐depth qualitative analysis of three cases involving crowd‐funding initiatives: SellaBand in the music business, Trampoline in financial services, and Kapipal in non‐profit services. These cases were selected to represent a diverse set of crowd‐funding operations that vary in terms of risk/return for the investor and the type of payoff associated to the investment.Findings – The research addresses two research questions: how and why do consumers turn into crowd‐funding ...
University of Miami1, University of Pennsylvania2, Johns Hopkins University3, University of Alabama4, St. John's University5, Tulane University6, Kaiser Permanente7, University of Michigan8, Wayne State University9, University of California, San Francisco10, University of Illinois at Chicago11, National Institutes of Health12
TL;DR: Elevated FGF-23 is an independent risk factor for end-stage renal disease in patients with relatively preserved kidney function and for mortality across the spectrum of chronic kidney disease.
Abstract: Context A high level of the phosphate-regulating hormone fibroblast growth factor 23 (FGF-23) is associated with mortality in patients with end-stage renal disease, but little is known about its relationship with adverse outcomes in the much larger population of patients with earlier stages of chronic kidney disease. Objective To evaluate FGF-23 as a risk factor for adverse outcomes in patients with chronic kidney disease. Design, Setting, and Participants A prospective study of 3879 participants with chronic kidney disease stages 2 through 4 who enrolled in the Chronic Renal Insufficiency Cohort between June 2003 and September 2008. Main Outcome Measures All-cause mortality and end-stage renal disease. Results At study enrollment, the mean (SD) estimated glomerular filtration rate (GFR) was 42.8 (13.5) mL/min/1.73 m 2 , and the median FGF-23 level was 145.5 RU/mL (interquartile range [IQR], 96-239 reference unit [RU]/mL). During a median follow-up of 3.5 years (IQR, 2.5-4.4 years), 266 participants died (20.3/1000 person-years) and 410 reached end-stage renal disease (33.0/1000 person-years). In adjusted analyses, higher levels of FGF-23 were independently associated with a greater risk of death (hazard ratio [HR], per SD of natural log-transformed FGF-23, 1.5; 95% confidence interval [CI], 1.3-1.7). Mortality risk increased by quartile of FGF-23: the HR was 1.3 (95% CI, 0.8-2.2) for the second quartile, 2.0 (95% CI, 1.2-3.3) for the third quartile, and 3.0 (95% CI, 1.8-5.1) for the fourth quartile. Elevated fibroblast growth factor 23 was independently associated with significantly higher risk of end-stage renal disease among participants with an estimated GFR between 30 and 44 mL/min/1.73 m 2 (HR, 1.3 per SD of FGF-23 natural log-transformed FGF-23; 95% CI, 1.04-1.6) and 45 mL/min/1.73 m 2 or higher (HR, 1.7; 95% CI, 1.1-2.4), but not less than 30 mL/min/1.73 m 2 . Conclusion Elevated FGF-23 is an independent risk factor for end-stage renal disease in patients with relatively preserved kidney function and for mortality across the spectrum of chronic kidney disease.
TL;DR: In this article, the authors investigated coral reefs, seagrasses and sediments that are acclimatized to low pH at three cool and shallow volcanic carbon dioxide seeps in Papua New Guinea.
Abstract: Experiments have shown that ocean acidification due to rising atmospheric carbon dioxide concentrations has deleterious effects on the performance of many marine organisms(1-4). However, few empirical or modelling studies have addressed the long-term consequences of ocean acidification for marine ecosystems(5-7). Here we show that as pH declines from 8.1 to 7.8 (the change expected if atmospheric carbon dioxide concentrations increase from 390 to 750 ppm, consistent with some scenarios for the end of this century) some organisms benefit, but many more lose out. We investigated coral reefs, seagrasses and sediments that are acclimatized to low pH at three cool and shallow volcanic carbon dioxide seeps in Papua New Guinea. At reduced pH, we observed reductions in coral diversity, recruitment and abundances of structurally complex framework builders, and shifts in competitive interactions between taxa. However, coral cover remained constant between pH 8.1 and similar to 7.8, because massive Porites corals established dominance over structural corals, despite low rates of calcification. Reef development ceased below pH 7.7. Our empirical data from this unique field setting confirm model predictions that ocean acidification, together with temperature stress, will probably lead to severely reduced diversity, structural complexity and resilience Of Indo-Pacific coral reefs within this century
Centre national de la recherche scientifique1, University of Miami2, Max Planck Society3, Columbia University4, Goddard Institute for Space Studies5, Met Office6, Pierre-and-Marie-Curie University7, Goddard Space Flight Center8, Universities Space Research Association9, Pacific Northwest National Laboratory10, National Center for Atmospheric Research11, Geophysical Fluid Dynamics Laboratory12, University of Oslo13, United States Department of Energy14, Utrecht University15, Wageningen University and Research Centre16, Florida State University17, University of Michigan18, Cornell University19, European Centre for Medium-Range Weather Forecasts20, University of Oxford21, Kyushu University22, University of California, Irvine23
TL;DR: In this article, the results of a broad intercomparison of a total of 15 global aerosol models within the AeroCom project are compared to observations related to desert dust aerosols, their direct radiative effect, and their impact on the biogeochemical cycle, i.e., aerosol optical depth and dust deposition.
Abstract: . This study presents the results of a broad intercomparison of a total of 15 global aerosol models within the AeroCom project. Each model is compared to observations related to desert dust aerosols, their direct radiative effect, and their impact on the biogeochemical cycle, i.e., aerosol optical depth (AOD) and dust deposition. Additional comparisons to Angstrom exponent (AE), coarse mode AOD and dust surface concentrations are included to extend the assessment of model performance and to identify common biases present in models. These data comprise a benchmark dataset that is proposed for model inspection and future dust model development. There are large differences among the global models that simulate the dust cycle and its impact on climate. In general, models simulate the climatology of vertically integrated parameters (AOD and AE) within a factor of two whereas the total deposition and surface concentration are reproduced within a factor of 10. In addition, smaller mean normalized bias and root mean square errors are obtained for the climatology of AOD and AE than for total deposition and surface concentration. Characteristics of the datasets used and their uncertainties may influence these differences. Large uncertainties still exist with respect to the deposition fluxes in the southern oceans. Further measurements and model studies are necessary to assess the general model performance to reproduce dust deposition in ocean regions sensible to iron contributions. Models overestimate the wet deposition in regions dominated by dry deposition. They generally simulate more realistic surface concentration at stations downwind of the main sources than at remote ones. Most models simulate the gradient in AOD and AE between the different dusty regions. However the seasonality and magnitude of both variables is better simulated at African stations than Middle East ones. The models simulate the offshore transport of West Africa throughout the year but they overestimate the AOD and they transport too fine particles. The models also reproduce the dust transport across the Atlantic in the summer in terms of both AOD and AE but not so well in winter-spring nor the southward displacement of the dust cloud that is responsible of the dust transport into South America. Based on the dependency of AOD on aerosol burden and size distribution we use model bias with respect to AOD and AE to infer the bias of the dust emissions in Africa and the Middle East. According to this analysis we suggest that a range of possible emissions for North Africa is 400 to 2200 Tg yr−1 and in the Middle East 26 to 526 Tg yr−1.
Université libre de Bruxelles1, University of Miami2, University of Alberta3, Suffolk University4, Bond University5, St. Joseph's Healthcare Hamilton6, Durham University7, Salt Lake Regional Medical Center8, University of Utah9, Oslo University Hospital10, State University of New York System11, University of California, Los Angeles12, University of Limerick13, Konyang University14, University of Nevada, Reno15, Washington State University16, University of the Pacific (United States)17
TL;DR: Myalgic encephalomyelitis: International Consensus Criteria (Review).
Abstract: 12 FatigueConsultationClinic,SaltLake RegionalMedicalCenter; 13 InternalMedicine,FamilyPractice,UniversityofUtah,SaltLakeCity,UT,USA; 14 ME ⁄CFSCenter,OsloUniversity HospitalHF,Norway; 15 DepartmentofPaediatrics,StateUniversityofNewYork,Buffalo,NY,USA; 16 Independent,Pavia,Italy; 17 Harbor-UCLA MedicalCenter,UniversityofCalifornia,LosAngeles,CA; 18 EVMedResearch,Lomita,CA,USA; 19 UniversityofLimerick,Limerick,Ireland; 20 Pain Clinic,KonyangUniversityHospital,Daejeon,Korea; 21 DonvaleSpecialistMedicalCentre,Donvale,Victoria,Australia; 22 Departmentsof Anesthesiology,NeurobiologyandAnatomy,UniversityofUtah,SaltLakeCity,UT,USA; 23 DepartmentofMedicinaNuclear,ClinicaLasCondes, Santiago,Chile; 24 WhittemorePetersonInstitute,UniversityofNevada,Reno,NV,USA; 25 MiwaNaikaClinic,Toyama,Japan; 26 A.Kirchenstein InstituteofMicrobiologyandVirology,RigaStradinsUniversity,Riga,Latvia; 27 DepartmentofBiochemistryBand 28 DepartmentofSportsSciences,UniversityofthePacific,Stockton,CAUSA
TL;DR: The current understanding of MSC biology, mechanism of action in cardiac repair, translational findings, and early clinical trial data of M SC therapy for cardiac disease are reviewed.
Abstract: Mesenchymal stem cells (MSCs) are a prototypical adult stem cell with capacity for self-renewal and differentiation with a broad tissue distribution. Initially described in bone marrow, MSCs have the capacity to differentiate into mesoderm- and nonmesoderm-derived tissues. The endogenous role for MSCs is maintenance of stem cell niches (classically the hematopoietic), and as such, MSCs participate in organ homeostasis, wound healing, and successful aging. From a therapeutic perspective, and facilitated by the ease of preparation and immunologic privilege, MSCs are emerging as an extremely promising therapeutic agent for tissue regeneration. Studies in animal models of myocardial infarction have demonstrated the ability of transplanted MSCs to engraft and differentiate into cardiomyocytes and vasculature cells, recruit endogenous cardiac stem cells, and secrete a wide array of paracrine factors. Together, these properties can be harnessed to both prevent and reverse remodeling in the ischemically injured ventricle. In proof-of-concept and phase I clinical trials, MSC therapy improved left ventricular function, induced reverse remodeling, and decreased scar size. This article reviews the current understanding of MSC biology, mechanism of action in cardiac repair, translational findings, and early clinical trial data of MSC therapy for cardiac disease.
TL;DR: Energy drinks have no therapeutic benefit, and many ingredients are understudied and not regulated, and concerns for potentially serious adverse effects in association with energy drink use are raised.
Abstract: OBJECTIVE: To review the effects, adverse consequences, and extent of energy drink consumption among children, adolescents, and young adults.
METHODS: We searched PubMed and Google using “energy drink,” “sports drink,” “guarana,” “caffeine,” “taurine,” “ADHD,” “diabetes,” “children,” “adolescents,” “insulin,” “eating disorders,” and “poison control center” to identify articles related to energy drinks. Manufacturer Web sites were reviewed for product information.
RESULTS: According to self-report surveys, energy drinks are consumed by 30% to 50% of adolescents and young adults. Frequently containing high and unregulated amounts of caffeine, these drinks have been reported in association with serious adverse effects, especially in children, adolescents, and young adults with seizures, diabetes, cardiac abnormalities, or mood and behavioral disorders or those who take certain medications. Of the 5448 US caffeine overdoses reported in 2007, 46% occurred in those younger than 19 years. Several countries and states have debated or restricted energy drink sales and advertising.
CONCLUSIONS: Energy drinks have no therapeutic benefit, and many ingredients are understudied and not regulated. The known and unknown pharmacology of agents included in such drinks, combined with reports of toxicity, raises concern for potentially serious adverse effects in association with energy drink use. In the short-term, pediatricians need to be aware of the possible effects of energy drinks in vulnerable populations and screen for consumption to educate families. Long-term research should aim to understand the effects in at-risk populations. Toxicity surveillance should be improved, and regulations of energy drink sales and consumption should be based on appropriate research.
TL;DR: The discovery of Notch in Drosophila melanogaster opened the door to an ever-widening understanding of cellular processes that are controlled or influenced by Notch signalling, and a role for Notch is well established in haematological malignancies.
Abstract: The discovery of Notch in Drosophila melanogaster nearly a century ago opened the door to an ever-widening understanding of cellular processes that are controlled or influenced by Notch signalling. As would be expected with such a pleiotropic pathway, the deregulation of Notch signalling leads to several pathological conditions, including cancer. A role for Notch is well established in haematological malignancies, and more recent studies have provided evidence for the importance of Notch activity in solid tumours. As it is thought to act as an oncogene in some cancers but as a tumour suppressor in others, the role of Notch in solid tumours seems to be highly context dependent.
TL;DR: It is reported that serum soluble urokinase receptor (suPAR) is elevated in two-thirds of subjects with primary FSGS, but not in people with other glomerular diseases, and that a higher concentration of suPAR before transplantation underlies an increased risk for recurrence of FSGS after transplantation.
Abstract: Focal segmental glomerulosclerosis (FSGS) is a cause of proteinuric kidney disease, compromising both native and transplanted kidneys. Treatment is limited because of a complex pathogenesis, including unknown serum factors. Here we report that serum soluble urokinase receptor (suPAR) is elevated in two-thirds of subjects with primary FSGS, but not in people with other glomerular diseases. We further find that a higher concentration of suPAR before transplantation underlies an increased risk for recurrence of FSGS after transplantation. Using three mouse models, we explore the effects of suPAR on kidney function and morphology. We show that circulating suPAR activates podocyte β(3) integrin in both native and grafted kidneys, causing foot process effacement, proteinuria and FSGS-like glomerulopathy. Our findings suggest that the renal disease only develops when suPAR sufficiently activates podocyte β(3) integrin. Thus, the disease can be abrogated by lowering serum suPAR concentrations through plasmapheresis, or by interfering with the suPAR-β(3) integrin interaction through antibodies and small molecules targeting either uPAR or β(3) integrin. Our study identifies serum suPAR as a circulating factor that may cause FSGS.
TL;DR: This paper describes a solution based on materials that integrate directly with the thin elastic membranes of otherwise conventional balloon catheters, to provide diverse, multimodal functionality suitable for clinical use.
Abstract: Developing advanced surgical tools for minimally invasive procedures represents an activity of central importance to improving human health. A key challenge is in establishing biocompatible interfaces between the classes of semiconductor device and sensor technologies that might be most useful in this context and the soft, curvilinear surfaces of the body. This paper describes a solution based on materials that integrate directly with the thin elastic membranes of otherwise conventional balloon catheters, to provide diverse, multimodal functionality suitable for clinical use. As examples, we present sensors for measuring temperature, flow, tactile, optical and electrophysiological data, together with radiofrequency electrodes for controlled, local ablation of tissue. Use of such 'instrumented' balloon catheters in live animal models illustrates their operation, as well as their specific utility in cardiac ablation therapy. The same concepts can be applied to other substrates of interest, such as surgical gloves.
TL;DR: Data suggest that perturbations in the PACAP–PAC1 pathway are involved in abnormal stress responses underlying PTSD, and sex-specific effects may occur via oestrogen regulation of ADCYAP1R1.
Abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) is known to broadly regulate the cellular stress response. In contrast, it is unclear if the PACAP-PAC1 receptor pathway has a role in human psychological stress responses, such as post-traumatic stress disorder (PTSD). Here we find, in heavily traumatized subjects, a sex-specific association of PACAP blood levels with fear physiology, PTSD diagnosis and symptoms in females. We examined 44 single nucleotide polymorphisms (SNPs) spanning the PACAP (encoded by ADCYAP1) and PAC1 (encoded by ADCYAP1R1) genes, demonstrating a sex-specific association with PTSD. A single SNP in a putative oestrogen response element within ADCYAP1R1, rs2267735, predicts PTSD diagnosis and symptoms in females only. This SNP also associates with fear discrimination and with ADCYAP1R1 messenger RNA expression in human brain. Methylation of ADCYAP1R1 in peripheral blood is also associated with PTSD. Complementing these human data, ADCYAP1R1 mRNA is induced with fear conditioning or oestrogen replacement in rodent models. These data suggest that perturbations in the PACAP-PAC1 pathway are involved in abnormal stress responses underlying PTSD. These sex-specific effects may occur via oestrogen regulation of ADCYAP1R1. PACAP levels and ADCYAP1R1 SNPs may serve as useful biomarkers to further our mechanistic understanding of PTSD.
SUNY Downstate Medical Center1, University of Mississippi2, Johns Hopkins University3, Children's National Medical Center4, Howard University5, Duke University6, University of Texas at Dallas7, Medical University of South Carolina8, University of Miami9, Emory University10, Boston Children's Hospital11, University of Alabama at Birmingham12, Georgia Regents University13, National Institutes of Health14
TL;DR: Hydroxycarbamide can now be considered for all very young children with sickle-cell anaemia, with some evidence for decreased acute chest syndrome, hospitalisation rates, and transfusion.
TL;DR: In this paper, a conceptual framework for investigating the antecedents and consequences of service innovation is proposed, and the authors test their proposed model using data from a sample of luxury hotels and find that collaborating with customers fosters innovation volume but not radicalness (and vice versa for collaborating with business partners).
Abstract: Research to date on service innovation is rooted primarily in traditional new product development focusing on tangible goods. In this article, the authors invoke insights from the emerging service-dominant logic (SDL) perspective and propose a conceptual framework for investigating the antecedents and consequences of service innovation. They then develop a set of hypotheses pertaining to potential predictors of two distinct facets of service innovation (volume and radicalness) and the impact of the latter on two measures of firm performance (revenue growth and profit growth). They test their proposed model using data from a sample of luxury hotels and find that (a) collaborating with customers fosters innovation volume but not radicalness (and vice versa for collaborating with business partners); (b) a firm’s customer orientation—both directly and in interaction with innovative orientation—contributes to innovation radicalness; (c) collaborating with contact employees enhances both innovation volume and r...
TL;DR: The European Space Agency's Planck satellite was launched on 14 May 2009, and has been surveying the sky stably and continuously since 13 August 2009 as mentioned in this paper, and it will continue to gather scientific data until the end of its cryogenic lifetime.
Abstract: The European Space Agency's Planck satellite was launched on 14 May 2009, and has been surveying the sky stably and continuously since 13 August 2009. Its performance is well in line with expectations, and it will continue to gather scientific data until the end of its cryogenic lifetime. We give an overview of the history of Planck in its first year of operations, and describe some of the key performance aspects of the satellite. This paper is part of a package submitted in conjunction with Planck's Early Release Compact Source Catalogue, the first data product based on Planck to be released publicly. The package describes the scientific performance of the Planck payload, and presents results on a variety of astrophysical topics related to the sources included in the Catalogue, as well as selected topics on diffuse emission.
Harvard University1, National Institutes of Health2, University of Miami3, French Institute of Health and Medical Research4, Erasmus University Rotterdam5, University of Texas Health Science Center at San Antonio6, Medical University of Graz7, Our Lady's Children's Hospital8, Memorial Sloan Kettering Cancer Center9
TL;DR: WT GISTs, particularly those in younger patients, have defects in SDH mitochondrial complex II, and in a subset of these patients, GIST seems to arise from germline-inactivating SDH mutations.
Abstract: Carney-Stratakis syndrome, an inherited condition predisposing affected individuals to gastrointestinal stromal tumor (GIST) and paraganglioma, is caused by germline mutations in succinate dehydrogenase (SDH) subunits B, C, or D, leading to dysfunction of complex II of the electron transport chain. We evaluated the role of defective cellular respiration in sporadic GIST lacking mutations in KIT or PDGFRA (WT). Thirty-four patients with WT GIST without a personal or family history of paraganglioma were tested for SDH germline mutations. WT GISTs lacking demonstrable SDH genetic inactivation were evaluated for SDHB expression by immunohistochemistry and Western blotting and for complex II activity. For comparison, SDHB expression was also determined in KIT mutant and neurofibromatosis-1–associated GIST, and complex II activity was also measured in SDH-deficient paraganglioma and KIT mutant GIST; 4 of 34 patients (12%) with WT GIST without a personal or family history of paraganglioma had germline mutations in SDHB or SDHC. WT GISTs lacking somatic mutations or deletions in SDH subunits had either complete loss of or substantial reduction in SDHB protein expression, whereas most KIT mutant GISTs had strong SDHB expression. Complex II activity was substantially decreased in WT GISTs. WT GISTs, particularly those in younger patients, have defects in SDH mitochondrial complex II, and in a subset of these patients, GIST seems to arise from germline-inactivating SDH mutations. Testing for germline mutations in SDH is recommended in patients with WT GIST. These findings highlight a potential central role of SDH dysregulation in WT GIST oncogenesis.
TL;DR: This study was a comprehensive, quantitative synthesis of the literature, using a total of 59 studies from 1947 to 2009 for analysis and indicated a significant and positive effect of physical activity on children's achievement and cognitive outcomes.
Abstract: It is common knowledge that physical activity leads to numerous health and psychological benefits. However, the relationship between children's physical activity and academic achievement has been debated in the literature. Some studies have found strong, positive relationships between physical activity and cognitive outcomes, while other studies have reported small, negative associations. This study was a comprehensive, quantitative synthesis of the literature, using a total of 59 studies from 1947 to 2009 for analysis. Results indicated a significant and positive effect of physical activity on children's achievement and cognitive outcomes, with aerobic exercise having the greatest effect. A number of moderator variables were also found to play a significant role in this relationship. Findings are discussed in light of improving children's academic performance and changing school-based policy.