983 research outputs found
Corrigendum to "Chemical apportionment of southern African aerosol mass and optical depth" published in Atmos. Chem. Phys., 9, 7643–7655, 2009
A correction to results by Magi (2009) is presented here. By combining the in situ measurements of speciated aerosol mass concentrations with concurrent measurements of total aerosol optical properties at a wavelength of 550 nm, it is shown that ~66 % of scattering is due to carbonaceous aerosol, where derived mass scattering cross sections (MSC) for OC and BC are 3.8 &plusmn; 0.5 m<sup>2</sup> g<sup>−1</sup> and 2.9 &plusmn; 0.8 m<sup>2</sup> g<sup>−1</sup>, respectively. Derived values of mass absorption cross sections (MAC) for OC and BC are 0.7 &plusmn; 0.2 m<sup>2</sup> g<sup>−1</sup> and 12.1 &plusmn; 0.8 m<sup>2</sup> g<sup>−1</sup>, respectively. The values of MAC imply that ~21 % of the mid-visible aerosol absorption in southern Africa is due to OC, with the remainder due to BC. SSA for BC and OC are about the same as Magi (2009). The results here are determined using an approach that accounts for the fact that OC and BC are partially scattering and absorbing
Galectin-3. One molecule for an alphabet of diseases, from A to Z
Galectin-3 (Gal-3) regulates basic cellular functions such as cell–cell and cell–matrix interactions, growth, proliferation, differentiation, and inflammation. It is not surprising, therefore, that this protein is involved in the pathogenesis of many relevant human diseases, including cancer, fibrosis, chronic inflammation and scarring affecting many different tissues. The papers published in the literature have progressively increased in number during the last decades, testifying the great interest given to this protein by numerous researchers involved in many different clinical contexts. Considering the crucial role exerted by Gal-3 in many different clinical conditions, Gal-3 is emerging as a new diagnostic, prognostic biomarker and as a new promising therapeutic target. The current review aims to extensively examine the studies published so far on the role of Gal-3 in all the clinical conditions and diseases, listed in alphabetical order, where it was analyzed
Reconstructions of biomass burning from sediment charcoal records to improve data-model comparisons
The location, timing, spatial extent, and frequency of wildfires are changing rapidly in many parts of the world, producing substantial impacts on ecosystems, people, and potentially climate. Paleofire records based on charcoal accumulation in sediments enable modern changes in biomass burning to be considered in their long-term context. Paleofire records also provide insights into the causes and impacts of past wildfires and emissions when analyzed in conjunction with other paleoenvironmental data and with fire models. Here we present new 1000 year and 22 000 year trends and gridded biomass burning reconstructions based on the Global Charcoal Database version 3, which includes 736 charcoal records (57 more than in version 2). The new gridded reconstructions reveal the spatial patterns underlying the temporal trends in the data, allowing insights into likely controls on biomass burning at regional to global scales. In the most recent few decades, biomass burning has sharply increased in both hemispheres, but especially in the north, where charcoal fluxes are now higher than at any other time during the past 22 000 {years}. We also discuss methodological issues relevant to data-model comparisons, and identify areas for future research. Spatially gridded versions of the global dataset from GCDv3 are provided to facilitate comparison with and validation of global fire simulations
Characterization of 1577 primary prostate cancers reveals novel biological and clinicopathologic insights into molecular subtypes.
BACKGROUND: Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 overexpression. Clinical assessment may aid in disease stratification, complementing available prognostic tests.
OBJECTIVE: To determine the analytical validity and clinicopatholgic associations of microarray-based molecular subtyping.
DESIGN, SETTING, AND PARTICIPANTS: We analyzed Affymetrix GeneChip expression profiles for 1577 patients from eight radical prostatectomy cohorts, including 1351 cases assessed using the Decipher prognostic assay (GenomeDx Biosciences, San Diego, CA, USA) performed in a laboratory with Clinical Laboratory Improvements Amendment certification. A microarray-based (m-) random forest ERG classification model was trained and validated. Outlier expression analysis was used to predict other mutually exclusive non-ERG ETS gene rearrangements (ETS(+)) or SPINK1 overexpression (SPINK1(+)).
OUTCOME MEASUREMENTS: Associations with clinical features and outcomes by multivariate logistic regression analysis and receiver operating curves.
RESULTS AND LIMITATIONS: The m-ERG classifier showed 95% accuracy in an independent validation subset (155 samples). Across cohorts, 45% of PCas were classified as m-ERG(+), 9% as m-ETS(+), 8% as m-SPINK1(+), and 38% as triple negative (m-ERG(-)/m-ETS(-)/m-SPINK1(-)). Gene expression profiling supports three underlying molecularly defined groups: m-ERG(+), m-ETS(+), and m-SPINK1(+)/triple negative. On multivariate analysis, m-ERG(+) tumors were associated with lower preoperative serum prostate-specific antigen and Gleason scores, but greater extraprostatic extension (p
CONCLUSIONS: A clinically available prognostic test (Decipher) can also assess PCa molecular subtypes, obviating the need for additional testing. Clinicopathologic differences were found among subtypes based on global expression patterns.
PATIENT SUMMARY: Molecular subtyping of prostate cancer can be achieved using extra data generated from a clinical-grade, genome-wide expression-profiling prognostic assay (Decipher). Transcriptomic and clinical analysis support three distinct molecular subtypes: (1) m-ERG(+), (2) m-ETS(+), and (3) m-SPINK1(+)/triple negative (m-ERG(-)/m-ETS(-)/m-SPINK1(-)). Incorporation of subtyping into a clinically available assay may facilitate additional applications beyond routine prognosis
Treatment challenges in and outside a network setting: Head and neck cancers
Head and neck cancer (HNC) is a rare disease that can affect different sites and is characterized by variable incidence and 5-year survival rates across Europe. Multiple factors need to be considered when choosing the most appropriate treatment for HNC patients, such as age, comorbidities, social issues, and especially whether to prefer surgery or radiation-based protocols. Given the complexity of this scenario, the creation of a highly specialized multidisciplinary team is recommended to guarantee the best oncological outcome and prevent or adequately treat any adverse effect. Data from literature suggest that the multidisciplinary team-based approach is beneficial for HNC patients and lead to improved survival rates. This result is likely due to improved diagnostic and staging accuracy, a more efficacious therapeutic approach and enhanced communication across disciplines. Despite the benefit of MTD, it must be noted that this approach requires considerable time, effort and financial resources and is usually more frequent in highly organized and high-volume centers. Literature data on clinical research suggest that patients treated in high-accrual centers report better treatment outcomes compared to patients treated in low-volume centers, where a lower radiotherapy-compliance and worst overall survival have been reported. There is general agreement that treatment of rare cancers such as HNC should be concentrated in high volume, specialized and multidisciplinary centers. In order to achieve this goal, the creation of international collaboration network is fundamental. The European Reference Networks for example aim to create an international virtual advisory board, whose objectives are the exchange of expertise, training, clinical collaboration and the reduction of disparities and enhancement of rationalize migration across Europe. The purpose of our work is to review all aspects and challenges in and outside this network setting planned for the management of HNC patients
Chalcogenide Glasses for All-optical Processing
Copyright © 2006 IEEEChalcogenide glasses, which contain S, Se or Te atoms combined with network forming elements such as Ge, As, Sb have the largest third order optical nonlinearity of any inorganic glass. As a result they are attractive candidates for fibre and waveguide devices for all-optical signal processing in the telecommunications bands. In this talk I will review our recent progress in all-optical devices such as regenerators, wavelength converters and other devices in chalcogenide glasses.B. Luther-Davies, S. J. Madden, D-Y Choi, R-P Wang, A. V. Rode, A. Prasad, R. A. Jarvis, D. Moss, B. Eggleton, C. Grillet, M. R. E. Lamont, E. Magi, V. Ta’eed, M. Shookooh-Saremi, N. Baker, I. Littler, L. Fu, M. Rochette, Y. Rua
Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways
OBJECTIVE Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels.
RESEARCH DESIGN AND METHODS We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening.
RESULTS Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10−26), HFE (rs1800562/P = 2.6 × 10−20), TMPRSS6 (rs855791/P = 2.7 × 10−14), ANK1 (rs4737009/P = 6.1 × 10−12), SPTA1 (rs2779116/P = 2.8 × 10−9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10−9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10−54), MTNR1B (rs1387153/P = 4.0 × 10−11), GCK (rs1799884/P = 1.5 × 10−20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10−18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA1c.
CONCLUSIONS GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c
Comprehensive population-based genome sequencing provides insight into hematopoietic regulatory mechanisms
Genetic variants affecting hematopoiesis can influence commonly measured blood cell traits. To identify factors that affect hematopoiesis, we performed association studies for blood cell traits in the population-based Estonian Biobank using high-coverage whole-genome sequencing (WGS) in 2,284 samples and SNP genotyping in an additional 14,904 samples. Using up to 7,134 samples with available phenotype data, our analyses identified 17 associations across 14 blood cell traits. Integration of WGS-based fine-mapping and complementary epigenomic datasets provided evidence for causal mechanisms at several loci, including at a previously undiscovered basophil count-associated locus near the master hematopoietic transcription factor CEBPA. The fine-mapped variant at this basophil count association near CEBPA overlapped an enhancer active in common myeloid progenitors and influenced its activity. In situ perturbation of this enhancer by CRISPR/Cas9 mutagenesis in hematopoietic stem and progenitor cells demonstrated that it is necessary for and specifically regulates CEBPA expression during basophil differentiation. We additionally identified basophil count-associated variation at another more pleiotropic myeloid enhancer near GATA2, highlighting regulatory mechanisms for ordered expression of master hematopoietic regulators during lineage specification. Our study illustrates how population-based genetic studies can provide key insights into poorly understood cell differentiation processes of considerable physiologic relevance.Peer reviewe
Estimating and managing the changing methodological parameters of self-report surveys of addictive behavior - based on the waves of the National Survey on Addiction Problems in Hungary
The standard nature of the procedures and tools of sampling and data collection cannot guarantee the stability of data reliability and validity because non-sampling errors are highly sensitive to social conditions. The present study provides a post-hoc attempt to estimate and manage the changing methodological parameters of self-report surveys of addictive behaviours (being highly subjected to changes in social conditions) to make data interpretation easier. The analysis is based on the data of two national Hungarian representative surveys assessing addiction problems in 2007 and 2015 (National Survey on Addiction Problems in Hungary [NSAPH]). Both surveys were conducted using a Hungarian nationwide representative sample aged 18-64 years applying similar procedures in data collection and-processing. Regarding data concerning substance use, both surveys included variables to estimate non-sampling errors in line with current international practices. The methodological parameters of NSAPH2015 showed an increase in non-sampling errors regarding substance use behaviour compared to NSAPH2007. The present paper elaborates an estimation procedure based on the assumption that when following a population, the proportion of people who have ever engaged in a specific type of addictive behaviour cannot be reduced in the given population over time. This also applies to cohorts followed by cross-sectional surveys among national representative samples, as far as lifetime prevalence and data on the age of first use/activity is available. To identify valid trends in different behaviours in epidemiological research assessing addictive behaviours or other sensitive data, researchers should provide the required conditions for controlling or correcting data by cohort analysis
Treatment challenges in and outside a specialist network setting: Pancreatic neuroendocrine tumours
Pancreatic Neuroendocrine Neoplasms comprise a group of rare tumours with special biology, an often indolent behaviour and particular diagnostic and therapeutic requirements. The specialized biochemical tests and radiological investigations, the complexity of surgical options and the variety of medical treatments that require individual tailoring, mandate a multidisciplinary approach that can be optimally achieved through an organized network. The present study describes currents concepts in the management of these tumours as well as an insight into the challenges of delivering the pathway in and outside a Network
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