Showing papers by "Dalhousie University published in 2014"
TL;DR: The American Association of Oral and Maxillofacial Surgeons (AAOMS) developed guidelines for medication-related osteonecrosis of the jaw (MRONJ) in 2007 and 2009 as mentioned in this paper.
2,176 citations
1,620 citations
Dalhousie University1, University of Alabama at Birmingham2, Mount Sinai Hospital3, University of Göttingen4, Manchester Academic Health Science Centre5, Hospital de Sant Pau6, Jikei University School of Medicine7, University of Iceland8, National Taiwan University9, University of Texas Health Science Center at San Antonio10, Novartis11
TL;DR: Secukinumab was effective for psoriasis in two randomized trials, validating interleukin-17A as a therapeutic target and the rates of infection were higher with secuk inumab than with placebo in both studies and were similar to those with etanercept.
Abstract: BACKGROUND: Interleukin-17A is considered to be central to the pathogenesis of psoriasis. We evaluated secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. METHODS: In two phase 3, double-blind, 52-week trials, ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis), we randomly assigned 738 patients (in the ERASURE study) and 1306 patients (in the FIXTURE study) to subcutaneous secukinumab at a dose of 300 mg or 150 mg (administered once weekly for 5 weeks, then every 4 weeks), placebo, or (in the FIXTURE study only) etanercept at a dose of 50 mg (administered twice weekly for 12 weeks, then once weekly). The objective of each study was to show the superiority of secukinumab over placebo at week 12 with respect to the proportion of patients who had a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) and a score of 0 (clear) or 1 (almost clear) on a 5-point modified investigator's global assessment (coprimary end points). RESULTS: The proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 81.6% with 300 mg of secukinumab, 71.6% with 150 mg of secukinumab, and 4.5% with placebo; in the FIXTURE study, the rates were 77.1% with 300 mg of secukinumab, 67.0% with 150 mg of secukinumab, 44.0% with etanercept, and 4.9% with placebo (P<0.001 for each secukinumab dose vs. comparators). The proportion of patients with a response of 0 or 1 on the modified investigator's global assessment at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 65.3% with 300 mg of secukinumab, 51.2% with 150 mg of secukinumab, and 2.4% with placebo; in the FIXTURE study, the rates were 62.5% with 300 mg of secukinumab, 51.1% with 150 mg of secukinumab, 27.2% with etanercept, and 2.8% with placebo (P<0.001 for each secukinumab dose vs. comparators). The rates of infection were higher with secukinumab than with placebo in both studies and were similar to those with etanercept. CONCLUSIONS: Secukinumab was effective for psoriasis in two randomized trials, validating interleukin-17A as a therapeutic target. (Funded by Novartis Pharmaceuticals; ERASURE and FIXTURE ClinicalTrials.gov numbers, NCT01365455 and NCT01358578, respectively.).
1,587 citations
TL;DR: This Perspective outlines the history, basic concepts, and present status of KS-DFT in chemical physics, and offers suggestions for its future development.
Abstract: Since its formal inception in 1964–1965, Kohn-Sham density-functional theory (KS-DFT) has become the most popular electronic structure method in computational physics and chemistry. Its popularity stems from its beautifully simple conceptual framework and computational elegance. The rise of KS-DFT in chemical physics began in earnest in the mid 1980s, when crucial developments in its exchange-correlation term gave the theory predictive power competitive with well-developed wave-function methods. Today KS-DFT finds itself under increasing pressure to deliver higher and higher accuracy and to adapt to ever more challenging problems. If we are not mindful, however, these pressures may submerge the theory in the wave-function sea. KS-DFT might be lost. I am hopeful the Kohn-Sham philosophical, theoretical, and computational framework can be preserved. This Perspective outlines the history, basic concepts, and present status of KS-DFT in chemical physics, and offers suggestions for its future development.
1,136 citations
TL;DR: STING-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in TMEM173, the stimulator of interferon genes (STING), andConstitutive up-regulation of phosphorylated STAT1 in patients' lymphocytes was reduced by JAK inhibitors.
Abstract: BACKGROUND The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation. METHODS We analyzed the DNA of an index patient with early-onset systemic inflammation, cutaneous vasculopathy, and pulmonary inflammation. We sequenced a candidate gene, TMEM173, encoding the stimulator of interferon genes (STING), in this patient and in five unrelated children with similar clinical phenotypes. Four children were evaluated clinically and immunologically. With the STING ligand cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), we stimulated peripheral-blood mononuclear cells and fibroblasts from patients and controls, as well as commercially obtained endothelial cells, and then assayed transcription of IFNB1, the gene encoding interferon-β, in the stimulated cells. We analyzed IFNB1 reporter levels in HEK293T cells cotransfected with mutant or nonmutant STING constructs. Mutant STING leads to increased phosphorylation of signal transducer and activator of transcription 1 (STAT1), so we tested the effect of Janus kinase (JAK) inhibitors on STAT1 phosphorylation in lymphocytes from the affected children and controls. RESULTS We identified three mutations in exon 5 of TMEM173 in the six patients. Elevated transcription of IFNB1 and other gene targets of STING in peripheral-blood mononuclear cells from the patients indicated constitutive activation of the pathway that cannot be further up-regulated with stimulation. On stimulation with cGAMP, fibroblasts from the patients showed increased transcription of IFNB1 but not of the genes encoding interleukin-1 (IL1), interleukin-6 (IL6), or tumor necrosis factor (TNF). HEK293T cells transfected with mutant constructs show elevated IFNB1 reporter levels. STING is expressed in endothelial cells, and exposure of these cells to cGAMP resulted in endothelial activation and apoptosis. Constitutive up-regulation of phosphorylated STAT1 in patients’ lymphocytes was reduced by JAK inhibitors. CONCLUSIONS STING-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in TMEM173. (Funded by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases; ClinicalTrials.gov number, NCT00059748.)
975 citations
United Nations Environment Programme1, Dalhousie University2, Bedford Institute of Oceanography3, Queen's University4, American Museum of Natural History5, BirdLife International6, University of Paris-Sud7, Netherlands Environmental Assessment Agency8, United Nations9, Utrecht University10, University of British Columbia11, Organisation for Economic Co-operation and Development12, The Lodge13, Marine Stewardship Council14, Global Biodiversity Information Facility15, University of Wisconsin-Madison16, University of Queensland17, Zoological Society of London18, Martin Luther University of Halle-Wittenberg19, International Union for Conservation of Nature and Natural Resources20, College of William & Mary21, Sapienza University of Rome22, University of Sussex23, University of Vienna24, Environment Agency25, Microsoft26
TL;DR: A comprehensive mid-term assessment of progress toward 20 biodiversity-related “Aichi Targets” to be achieved within a decade is provided using 55 indicator data sets and pinpoints the problems and areas that will need the most attention in the next few years.
Abstract: In 2010, the international community, under the auspices of the Convention on Biological Diversity, agreed on 20 biodiversity-related “Aichi Targets” to be achieved within a decade. We provide a comprehensive mid-term assessment of progress toward these global targets using 55 indicator data sets. We projected indicator trends to 2020 using an adaptive statistical framework that incorporated the specific properties of individual time series. On current trajectories, results suggest that despite accelerating policy and management responses to the biodiversity crisis, the impacts of these efforts are unlikely to be reflected in improved trends in the state of biodiversity by 2020. We highlight areas of societal endeavor requiring additional efforts to achieve the Aichi Targets, and provide a baseline against which to assess future progress.
970 citations
University of British Columbia1, Canadian Institute for Advanced Research2, Monterey Bay Aquarium Research Institute3, Stony Brook University4, University of California, San Diego5, Brown University6, Marine Biological Laboratory7, University of Washington8, Dalhousie University9, National Center for Genome Resources10, Alfred Wegener Institute for Polar and Marine Research11, Rutgers University12, Texas A&M University13, University of Southern California14, University of Delaware15, Victoria University of Wellington16, University of Paris-Sud17, Columbia University18, University of Oslo19, University of Hawaii at Manoa20, University of Prince Edward Island21, University of Rhode Island22, Woods Hole Oceanographic Institution23, Max Planck Society24, Jacobs University Bremen25, Smith College26, University of South Alabama27, Saint Petersburg State University28, University of Geneva29, University of Connecticut30, Laval University31, University of Guelph32, University of North Carolina at Chapel Hill33, University of New Brunswick34, University of Camerino35, University of East Anglia36, Stazione Zoologica Anton Dohrn37, University of Georgia38, University of Technology, Sydney39, University of Puerto Rico40, University of Pisa41, Centre national de la recherche scientifique42, Colorado School of Mines43, Lund University44, University of Western Ontario45, California State University46, University of Texas at Austin47, Los Alamos National Laboratory48, Pierre-and-Marie-Curie University49, University of Oklahoma50, Plymouth Marine Laboratory51, Bigelow Laboratory For Ocean Sciences52, Princeton University53
TL;DR: In this paper, the authors describe a resource of 700 transcriptomes from marine microbial eukaryotes to help understand their role in the world's oceans and their biology, evolution, and ecology.
Abstract: Current sampling of genomic sequence data from eukaryotes is relatively poor, biased, and inadequate to address important questions about their biology, evolution, and ecology; this Community Page describes a resource of 700 transcriptomes from marine microbial eukaryotes to help understand their role in the world's oceans.
852 citations
TL;DR: Satellite observations provide insight into global long-term changes in ambient PM2.5 concentrations, and significant agreement between satellite-derived estimates and ground-based measurements outside North America and Europe suggests that true global concentrations could be even greater.
Abstract: Background: More than a decade of satellite observations offers global information about the trend and magnitude of human exposure to fine particulate matter (PM2.5).Objective: In this study, we de...
741 citations
TL;DR: The ENIGMA Consortium has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected.
Abstract: The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
713 citations
TL;DR: In two separate mussel analyses, significantly more microplastics were enumerated in farmed mussels compared to wild ones, and concentrations from polychaete fecal casts resembled concentrations quantified from low tide sediments.
624 citations
TL;DR: This work synthesized iron-nickel hydroxide–platinum (transition metal-OH-Pt) nanoparticles with diameters below 5 nanometers and showed that they are highly efficient for carbon monoxide (CO) oxidation catalysis at room temperature.
Abstract: Ministry of Science and Technology of China [2011CB932403]; National Nature Science Foundation of China [21131005, 20925103, 21373167, 21033006, 21333008]; Natural Sciences and Engineering Research Council of Canada
TL;DR: Analysis of the genomes of 30 Lachnospiraceae isolates demonstrates that adaptation to an ecological niche and acquisition of defining functional roles within a microbiome can arise through a combination of both habitat-specific gene loss and LGT.
Abstract: Several bacterial families are known to be highly abundant within the human microbiome, but their ecological roles and evolutionary histories have yet to be investigated in depth. One such family, Lachnospiraceae (phylum Firmicutes, class Clostridia) is abundant in the digestive tracts of many mammals and relatively rare elsewhere. Members of this family have been linked to obesity and protection from colon cancer in humans, mainly due to the association of many species within the group with the production of butyric acid, a substance that is important for both microbial and host epithelial cell growth. We examined the genomes of 30 Lachnospiraceae isolates to better understand the origin of butyric acid capabilities and other ecological adaptations within this group. Butyric acid production-related genes were detected in fewer than half of the examined genomes with the distribution of this function likely arising in part from lateral gene transfer (LGT). An investigation of environment-specific functional signatures indicated that human gut-associated Lachnospiraceae possess genes for endospore formation, whereas other members of this family lack key sporulation-associated genes, an observation supported by analysis of metagenomes from the human gut, oral cavity, and bovine rumen. Our analysis demonstrates that adaptation to an ecological niche and acquisition of defining functional roles within a microbiome can arise through a combination of both habitat-specific gene loss and LGT.
TL;DR: Using density functional theory, inorganic passivants that bind strongly to the CQD surface and repel oxidative attack are identified that are used to build an air-stable n-type inverted quantum junction device and a solar power conversion efficiency as high as 8%.
Abstract: Colloidal quantum dots (CQDs) offer promise in flexible electronics, light sensing and energy conversion. These applications rely on rectifying junctions that require the creation of high-quality CQD solids that are controllably n-type (electron-rich) or p-type (hole-rich). Unfortunately, n-type semiconductors made using soft matter are notoriously prone to oxidation within minutes of air exposure. Here we report high-performance, air-stable n-type CQD solids. Using density functional theory we identify inorganic passivants that bind strongly to the CQD surface and repel oxidative attack. A materials processing strategy that wards off strong protic attack by polar solvents enabled the synthesis of an air-stable n-type PbS CQD solid. This material was used to build an air-processed inverted quantum junction device, which shows the highest current density from any CQD solar cell and a solar power conversion efficiency as high as 8%. We also feature the n-type CQD solid in the rapid, sensitive, and specific detection of atmospheric NO2. This work paves the way for new families of electronic devices that leverage air-stable quantum-tuned materials.
TL;DR: Offspring of parents with SMI are at increased risk for a range of psychiatric disorders and one third of them may develop a SMI by early adulthood.
Abstract: Objective Offspring of parents with severe mental illness (SMI; schizophrenia, bipolar disorder, major depressive disorder) are at an increased risk of developing mental illness. We aimed to quantify the risk of mental disorders in offspring and determine whether increased risk extends beyond the disorder present in the parent. Method Meta-analyses of absolute and relative rates of mental disorders in offspring of parents with schizophrenia, bipolar disorder, or depression in family high-risk studies published by December 2012. Results We included 33 studies with 3863 offspring of parents with SMI and 3158 control offspring. Offspring of parents with SMI had a 32% probability of developing SMI (95% CI: 24%-42%) by adulthood (age >20). This risk was more than twice that of control offspring (risk ratio [RR] 2.52; 95% CI 2.08-3.06, P Conclusions Offspring of parents with SMI are at increased risk for a range of psychiatric disorders and one third of them may develop a SMI by early adulthood.
University of New South Wales1, Newcastle University2, University of Cambridge3, University of Gothenburg4, Nizam's Institute of Medical Sciences5, University of Toronto6, Harvard University7, Duke University8, National University of Singapore9, University of Southern California10, University of Pittsburgh11, University of California, San Diego12, Lille University of Science and Technology13, University of Iowa14, VU University Medical Center15, Dalhousie University16
TL;DR: The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathologic validation studies and can be harmonized with the DSM-5 criteria.
Abstract: Author(s): Sachdev, Perminder; Kalaria, Raj; O'Brien, John; Skoog, Ingmar; Alladi, Suvarna; Black, Sandra E; Blacker, Deborah; Blazer, Dan G; Chen, Christopher; Chui, Helena; Ganguli, Mary; Jellinger, Kurt; Jeste, Dilip V; Pasquier, Florence; Paulsen, Jane; Prins, Niels; Rockwood, Kenneth; Roman, Gustavo; Scheltens, Philip; Internationlal Society for Vascular Behavioral and Cognitive Disorders | Abstract: BackgroundSeveral sets of diagnostic criteria have been published for vascular dementia since the 1960s. The continuing ambiguity in vascular dementia definition warrants a critical reexamination.MethodsParticipants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the fifth revision of Diagnostic and Statistical Manual (DSM-5) Task Force.ResultsCognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent cooccurrence of Alzheimer disease pathology emphasized.ConclusionsThe proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathologic validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved.
TL;DR: A new class of upconversion nanocrystals adopting an orthorhombic crystallographic structure in which the lanthanide ions are distributed in arrays of tetrad clusters is described, which enables the preservation of excitation energy within the sublattice domain and effectively minimizes the migration ofexcitation energy to defects.
Abstract: Lanthanide-doped nanocrystals can be used to upconvert infrared radiation into visible light, and are thought to be promising for a range of photonic and biological imaging applications. It is now shown that the upconversion efficiency can be improved by appropriately clustering the lanthanide ions on different structural sublattices.
TL;DR: Data indicate BR is noninferior to standard therapy with regard to clinical response with an acceptable safety profile, and this trial was registered at www.clinicaltrials.gov as #NCT00877006.
Stockholm University1, Royal Swedish Academy of Sciences2, Stanford University3, WorldFish4, Dalhousie University5, Columbia University6, Princeton University7, University of Oslo8, University of Minnesota9, Wageningen University and Research Centre10, Commonwealth Scientific and Industrial Research Organisation11, Athens University of Economics and Business12, Tilburg University13
TL;DR: This work explores how current interconnections between the aquaculture, crop, livestock, and fisheries sectors act as an impediment to, or an opportunity for, enhanced resilience in the global food system given increased resource scarcity and climate change.
Abstract: Aquaculture is the fastest growing food sector and continues to expand alongside terrestrial crop and livestock production. Using portfolio theory as a conceptual framework, we explore how current interconnections between the aquaculture, crop, livestock, and fisheries sectors act as an impediment to, or an opportunity for, enhanced resilience in the global food system given increased resource scarcity and climate change. Aquaculture can potentially enhance resilience through improved resource use efficiencies and increased diversification of farmed species, locales of production, and feeding strategies. However, aquaculture’s reliance on terrestrial crops and wild fish for feeds, its dependence on freshwater and land for culture sites, and its broad array of environmental impacts diminishes its ability to add resilience. Feeds for livestock and farmed fish that are fed rely largely on the same crops, although the fraction destined for aquaculture is presently small (∼4%). As demand for high-value fed aquaculture products grows, competition for these crops will also rise, as will the demand for wild fish as feed inputs. Many of these crops and forage fish are also consumed directly by humans and provide essential nutrition for low-income households. Their rising use in aquafeeds has the potential to increase price levels and volatility, worsening food insecurity among the most vulnerable populations. Although the diversification of global food production systems that includes aquaculture offers promise for enhanced resilience, such promise will not be realized if government policies fail to provide adequate incentives for resource efficiency, equity, and environmental protection.
TL;DR: The results indicate that the luminescence of Au22(SR)18 originates from the long Au(I)-thiolate motifs on the NC surface via the aggregation-induced emission pathway, and structure prediction by density functional theory suggests that Au 22( SR)18 has two RS-[Au-SR]3 and two RS-SR4 motifs, interlocked and capped on a prolate Au8 core.
Abstract: The luminescence property of thiolated gold nanoclusters (Au NCs) is thought to involve the Au(I)-thiolate motifs on the NC surface; however, this hypothesis remains largely unexplored because of the lack of precise molecular composition and structural information of highly luminescent Au NCs. Here we report a new red-emitting thiolated Au NC, which has a precise molecular formula of Au22(SR)18 and exhibits intense luminescence. Interestingly, this new Au22(SR)18 species shows distinctively different absorption and emission features from the previously reported Au22(SR)16, Au22(SR)17, and Au25(SR)18. In stark contrast, Au22(SR)18 luminesces intensely at ∼665 nm with a high quantum yield of ∼8%, while the other three Au NCs show very weak luminescence. Our results indicate that the luminescence of Au22(SR)18 originates from the long Au(I)-thiolate motifs on the NC surface via the aggregation-induced emission pathway. Structure prediction by density functional theory suggests that Au22(SR)18 has two RS-[Au-...
University of Toronto1, University of British Columbia2, Foothills Medical Centre3, Montreal Heart Institute4, Ottawa Hospital Research Institute5, Sunnybrook Health Sciences Centre6, University of Alberta7, McMaster University8, Dalhousie University9, Women's College Hospital10, University Health Network11
TL;DR: The Canadian Cardiovascular Society AF Guidelines Committee judged that sufficient new information regarding AF management had become available since 2012 to warrant an update to the guidelines, and updated the guidelines for stroke prevention principles and rate and rhythm control including catheter ablation.
TL;DR: The results demonstrate the utility of this architecture for generating promising materials to be integrated into organic photovoltaic devices, call attention to areas for improvement, and provide guiding principles to sustain the steady increases necessary to move this technology forward.
Abstract: Organic semiconductors incorporated into solar cells using a bulk heterojunction (BHJ) construction show promise as a cleaner answer to increasing energy needs throughout the world. Organic solar c...
Jewish General Hospital1, McGill University2, University of Ottawa3, Ottawa Hospital Research Institute4, London Health Sciences Centre5, Capital District Health Authority6, Dalhousie University7, Tufts University8, Tufts Medical Center9, Université de Montréal10, St Mary's Hospital11, Montreal General Hospital12, University Health Network13, Karolinska Institutet14, McMaster University15, Hôpital Maisonneuve-Rosemont16, University of Manitoba17, St. Joseph Hospital18, Hurley Medical Center19, Sunnybrook Health Sciences Centre20, University of Oklahoma21, Duke University22
TL;DR: ECS did not prevent PTS after a first proximal DVT, hence the findings do not support routine wearing of ECS after DVT.
TL;DR: Several identified unmet needs warrant additional attention and action, including improved severity assessment, PsA screening, patient awareness, and treatment options.
Abstract: Background Available psoriasis surveys offer valuable information about psoriasis and psoriatic arthritis (PsA), but are limited by methodology or enrollment requirements. Objective To further the understanding of the unmet needs of psoriasis and PsA patients. Methods This was a large, multinational, population-based survey of psoriasis and/or PsA patients in North America and Europe. Patients were selected by list-assisted random digit dialing and did not have to currently be under the care of a health care provider, a patient organization member, or receiving treatment; 139,948 households were screened and 3426 patients completed the survey. Results The prevalence of psoriasis/PsA ranged from 1.4% to 3.3%; 79% had psoriasis alone and 21% had PsA. When rating disease severity at its worst, 27% (psoriasis) and 53% (PsA ± psoriasis) of patients rated it as severe. Psoriasis patients indicated that their most bothersome signs or symptoms were itching (43%), scales (23%), and flaking (20%). Of psoriasis patients, 45% had not seen a physician in a year; >80% of psoriasis patients with ≥4 palms body surface area and 59% of PsA patients were receiving no treatment or topical treatment only. Of patients who had received oral or biologic therapy, 57% and 45%, respectively, discontinued therapy, most often for safety/tolerability reasons and a lack/loss of efficacy. Limitations The survey lacked a control group, did not account for ethnic and health care system differences across countries, and was limited by factors associated with any patient survey, including accurate recall and interpretation of questions. Conclusions Several identified unmet needs warrant additional attention and action, including improved severity assessment, PsA screening, patient awareness, and treatment options.
TL;DR: Development and expanded use of methods capable of detecting evolutionary change are recommended, such as the long term study of selection coefficients and temporal shifts in reaction norms, and increased attention to forecasting adaptive change in response to the synergistic interactions of the multiple selection pressures likely to be associated with climate change.
Abstract: The physical and ecological ‘fingerprints’ of anthropogenic climate change over the past century are now well documented in many environments and taxa. We reviewed the evidence for phenotypic responses to recent climate change in fish. Changes in the timing of migration and reproduction, age at maturity, age at juvenile migration, growth, survival and fecundity were associated primarily with changes in temperature. Although these traits can evolve rapidly, only two studies attributed phenotypic changes formally to evolutionary mechanisms. The correlation-based methods most frequently employed point largely to ‘fine-grained’ population responses to environmental variability (i.e. rapid phenotypic changes relative to generation time), consistent with plastic mechanisms. Ultimately, many species will likely adapt to long-term warming trends overlaid on natural climate oscillations. Considering the strong plasticity in all traits studied, we recommend development and expanded use of methods capable of detecting evolutionary change, such as the long term study of selection coefficients and temporal shifts in reaction norms, and increased attention to forecasting adaptive change in response to the synergistic interactions of the multiple selection pressures likely to be associated with climate change.
TL;DR: This meta-analysis provides convergent evidence that texting compromises the safety of the driver, passengers and other road users and combined efforts, including legislation, enforcement, blocking technologies, parent modeling, social media, social norms and education, will be required to prevent continued deaths and injuries.
TL;DR: In this article, the most recent progress over the last couple of years towards developing n-type organic small molecules utilized in BHJ devices in order to provide insight towards improving the overall performance of OPVs.
Abstract: Organic, planar, and electron deficient small molecules were utilized as acceptors in the first reported bilayer heterojunction solar cells, however, current state-of-the-art organic photovoltaic (OPV) cells utilize fullerene derivatives as acceptor molecules. Recently, intensive efforts have been directed towards the development and understanding of soluble, non-fullerene, organic small molecules to fabricate bulk heterojunction (BHJ) solar cells. These efforts have been aimed at overcoming the inherent limitations of fullerene compounds such as the limited spectral breadth, air instability, and the typically higher production costs of fullerenes. In this focused review, we have highlighted the most recent progress over the last couple of years towards developing n-type organic small molecules utilized in BHJ devices in order to provide insight towards improving the overall performance of OPVs.
Durham University1, Max Planck Society2, University of Bonn3, Pennsylvania State University4, European Southern Observatory5, Dalhousie University6, University of Hertfordshire7, University of Vienna8, University College London9, University of Edinburgh10, Chalmers University of Technology11, University of Copenhagen12, Leiden University13
TL;DR: In this article, the authors exploit the Atacama Large Millimeter Array (ALMA) 870 mu m observations of sub-millimetre sources in the Extended Chandra Deep Field South (EDF South) to investigate the far-infrared properties of high-redshift sub millimetre galaxies (SMGs).
Abstract: We exploit Atacama Large Millimeter Array (ALMA) 870 mu m observations of sub-millimetre sources in the Extended Chandra Deep Field South to investigate the far-infrared properties of high-redshift sub-millimetre galaxies (SMGs). Using the precisely located 870 mu m ALMA positions of 99 SMGs, together with 24 mu m and radio imaging, we deblend the Herschel/SPIRE imaging to extract their far-infrared fluxes and colours. The median redshifts for ALMA LESS (ALESS) SMGs which are detected in at least two SPIRE bands increases with wavelength of the peak in their spectral energy distributions (SEDs), with z = 2.3 +/- 0.2, 2.5 +/- 0.3 and 3.5 +/- 0.5 for the 250, 350 and 500 mu m peakers, respectively. 34 ALESS SMGs do not have a >3 sigma counterpart at 250, 350 or 500 mu m. These galaxies have a median photometric redshift derived from the rest-frame UV-mid-infrared SEDs of z = 3.3 +/- 0.5, which is higher than the full ALESS SMG sample; z = 2.5 +/- 0.2. We estimate the far-infrared luminosities and characteristic dust temperature of each SMG, deriving L-IR = (3.0 +/- 0.3) x 10(12) L-circle dot (SFR = 300 +/- 30 M-circle dot yr(-1)) and T-d = 32 +/- 1 K. The characteristic dust temperature of these high-redshift SMGs is Delta T-d = 3-5K lower than comparably luminous galaxies at z = 0, reflecting the more extended star formation in these systems. We show that the contribution of S-870 mu m >= 1 mJy SMGs to the cosmic star formation budget is 20 per cent of the total over the redshift range z similar to 1-4. Adopting an appropriate gas-to-dust ratio, we estimate a typical molecular mass of the ALESS SMGs of M-H2 = (4.2 +/- 0.4) x 10(10) M-circle dot. Finally, we show that SMGs with S-870 mu m > 1 mJy (L-IR greater than or similar to 10(12) L-circle dot) contain similar to 10 per cent of the z similar to 2 volume-averaged H-2 mass density.
University of British Columbia1, University of Alabama at Birmingham2, Ohio State University3, Cornell University4, University of Florida5, University of Southern California6, University of Colorado Denver7, Cincinnati Children's Hospital Medical Center8, Thomas Jefferson University9, Dalhousie University10, Children's Hospital of Wisconsin11, Johns Hopkins University12, New York University13
TL;DR: Longer-term follow-up confirms the initial observation of substantially good outcomes for children and adolescents with Ph+ ALL treated with imatinib plus intensive chemotherapy with no advantage for allogeneic BMT.
Abstract: We previously reported preliminary findings that post induction imatinib mesylate (340 mg/m2/day), in combination with intensive chemotherapy, resulted in outcomes similar to blood and marrow transplant (BMT) for pediatric patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We now report 5-year outcomes of imatinib plus intensive chemotherapy in 91 children (1–21 years) with and without allogeneic BMT (N=91). We explore the impacts of additional chromosomal abnormalities and minimal residual disease (MRD) by flow cytometry on outcomes. The 5-year disease-free survival was similar for Cohort 5 patients, treated with chemotherapy plus imatinib (70%±12%, n=28), sibling donor BMT patients (65%±11%, n=21) and unrelated donor BMT patients (59±15%; P=0.60, n=13). Patients with additional cytogenetic abnormalities had worse outcomes (P=0.05). End induction (pre-imatinib) MRD was not prognostic for Cohort 5 or allogeneic BMT patients, although limited by small numbers. The re-induction rate following relapse was similar to other higher-risk ALL groups. Longer-term follow-up confirms our initial observation of substantially good outcomes for children and adolescents with Ph+ ALL treated with imatinib plus intensive chemotherapy with no advantage for allogeneic BMT.
TL;DR: An easily accessible peripheral blood biomarker may contribute to improvement in outcomes of major depressive disorder by personalizing treatment choice.
Abstract: OBJECTIVE: Major depressive disorder has been linked with inflammatory processes, but it is unclear whether individual differences in levels of inflammatory biomarkers could help match patients to treatments that are most likely to be beneficial. The authors tested the hypothesis that C-reactive protein (CRP), a commonly available marker of systemic inflammation, predicts differential response to escitalopram (a serotonin reuptake inhibitor) and nortriptyline (a norepinephrine reuptake inhibitor). METHOD: The hypothesis was tested in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study, a multicenter open-label randomized clinical trial. CRP was measured with a high-sensitivity method in serum samples from 241 adult men and women with major depressive disorder randomly allocated to 12-week treatment with escitalopram (N=115) or nortriptyline (N=126). The primary outcome measure was the score on the Montgomery-Asberg Depression Rating Scale (MADRS), administered weekly. RESULTS: CRP level at baseline differentially predicted treatment outcome with the two antidepressants (CRP-drug interaction: β=3.27, 95% CI=1.65, 4.89). For patients with low levels of CRP (<1 mg/L), improvement on the MADRS score was 3 points higher with escitalopram than with nortriptyline. For patients with higher CRP levels, improvement on the MADRS score was 3 points higher with nortriptyline than with escitalopram. CRP and its interaction with medication explained more than 10% of individual-level variance in treatment outcome. CONCLUSIONS: An easily accessible peripheral blood biomarker may contribute to improvement in outcomes of major depressive disorder by personalizing treatment choice.
TL;DR: Differences in functions related to host nutrition and drug pharmacology vary in an age-dependent manner, suggesting that the availability and timing of essential functions may differ significantly with age and frailty.
Abstract: The changes that occur in the microbiome of aging individuals are unclear, especially in light of the imperfect correlation of frailty with age. Studies in older human subjects have reported subtle effects, but these results may be confounded by other variables that often change with age such as diet and place of residence. To test these associations in a more controlled model system, we examined the relationship between age, frailty, and the gut microbiome of female C57BL/6 J mice. The frailty index, which is based on the evaluation of 31 clinical signs of deterioration in mice, showed a near-perfect correlation with age. We observed a statistically significant relationship between age and the taxonomic composition of the corresponding microbiome. Consistent with previous human studies, the Rikenellaceae family, which includes the Alistipes genus, was the most significantly overrepresented taxon within middle-aged and older mice. The functional profile of the mouse gut microbiome also varied with host age and frailty. Bacterial-encoded functions that were underrepresented in older mice included cobalamin (B12) and biotin (B7) biosynthesis, and bacterial SOS genes associated with DNA repair. Conversely, creatine degradation, associated with muscle wasting, was overrepresented within the gut microbiomes of the older mice, as were bacterial-encoded β-glucuronidases, which can influence drug-induced epithelial cell toxicity. Older mice also showed an overabundance of monosaccharide utilization genes relative to di-, oligo-, and polysaccharide utilization genes, which may have a substantial impact on gut homeostasis. We have identified taxonomic and functional patterns that correlate with age and frailty in the mouse microbiome. Differences in functions related to host nutrition and drug pharmacology vary in an age-dependent manner, suggesting that the availability and timing of essential functions may differ significantly with age and frailty. Future work with larger cohorts of mice will aim to separate the effects of age and frailty, and other factors.