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Sökning: WFRF:(Ruiz Patricia)

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1.
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2.
  • Cruz, Raquel, et al. (författare)
  • Novel genes and sex differences in COVID-19 severity
  • 2022
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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3.
  • Ferrando, Carlos, et al. (författare)
  • Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy : a randomised controlled trial
  • 2020
  • Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 124:1, s. 110-120
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. Methods: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. Results: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. Conclusions: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found.
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4.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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5.
  • Perez-Nadales, Elena, et al. (författare)
  • Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales : The impact of cytomegalovirus disease and lymphopenia
  • 2020
  • Ingår i: American Journal of Transplantation. - : WILEY. - 1600-6135 .- 1600-6143. ; 20:6, s. 1629-1641
  • Tidskriftsartikel (refereegranskat)abstract
    • Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score >= 8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score >= 8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.
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6.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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7.
  • Abolfathi, Bela, et al. (författare)
  • The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
  • 2018
  • Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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8.
  • Alejandro Zamora-Briseno, Jesus, et al. (författare)
  • iTRAQ-Based Proteomic Profile Analysis of the Hepatopancreas of Caribbean Spiny Lobsters Infected WithPanulirus argusVirus 1 : Metabolic and Physiological Implications
  • 2020
  • Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • The Caribbean spiny lobsterPanulirus argus(Latreille, 1084) sustains economically valuable fisheries throughout the wider Caribbean region. This species is currently affected by the pathogenic virusPanulirus argusVirus 1 (PaV1) that causes a systemic and chronic-degenerative infection in juvenile spiny lobstersP. argus. To date, there is no available information regarding the host alterations induced by this pathogen at the molecular level. In the present study, comparative proteomic analyses of the changes in the hepatopancreas between infected and non-infected juvenile lobsters were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ) coupled to synchronous precursor selection (SPS)-based MS3. We identified a total of 636 proteins, being 68 down-regulated and 71 up-regulated proteins. Among the down-regulated proteins, we identified several enzymes involved in the metabolism of hormones and lipids, digestive proteases and glycosidases, while proteins associated with the histone core, protein synthesis, immune response and RNA regulation were up-regulated. Several misregulated enzymes involved in the regulation of neuromodulators were also identified. RT-qPCR assays were used to validate the expression of transcripts encoding for selected differential proteins that were in concordance to proteomic data, as well as the tendency observed in the enzymatic activities of trypsin, chymotrypsin, and glycosidase. In a similar way, we observed glycogen reduction in muscle, and an increase in plasma acylglycerides and glucose, which may be explained by proteomic data. This study provides the first insight into the molecular changes in the hepatopancreas of Caribbean spiny lobsters associated to PaV1 infection. Data provided herein would help to clarify the origin of the molecular misregulations observed at macroscopic level in this host-pathogen interaction.
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9.
  • Arauz-Ruiz, Patricia (författare)
  • Molecular epidemiology of hepatitis A and hepatitis B virus in central America
  • 2002
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The genetic variability was determined for hepatitis A virus (HAV) and hepatitis B virus (HBV) strains from cases of acute and chronic hepatitis in Central America (CA). The genetic relatedness was established for the' strains to strains from other parts of the world. Molecular typing of HAV was performed by sequence analysis of the 5'-end of the VP1 region. HAV strains from CA were found to belong to genotype 1A. The strains were mostly similar to each other, and unrelated to subtype 1 A strains from other parts of the world. Based on their amino acid sequence four HAV strains, all related to strain CR326 sampled in Costa Rica in the 60s, were found to have been circulating in the area during the last three decades. However, on basis of nucleotide variability the isolates from two common source outbreaks in Costa Rica could be distinguished from the isolates of background sporadic cases. The genotyping of HBV was accomplished by partial sequencing of the S gene, followed by comparison of the predicted amino acid substitutions of the obtained sequences with the substitutions known conserved for each genotype. Genotype F was found in 79% of the strains and genotypes A, D and C were represented by 14%, 6% and 1 % of the strains, respectively. Phylogenetic analysis of the small S gene showed that genotype A strains from CA belonged to two different clusters, one including strains from Europe and USA, while one comprised strains with Afro-Asian origin. One genotype C strain was related to strains from South East Asia. Interestingly, the genotype D strains were related to strains from intravenous drug addicts in Europe. Within genotype F three genetic clusters were initialle disclosed. The major cluster was formed by 18 strains from CA and one strain from Alaska. A second cluster included two strains from CA and six from South America and Europe. Two Nicaraguan strains formed the third cluster, which were that divergent that they might represent a new genotype. The deduced amino acid sequence of the small S showed that all but one of the genotype F strains from CA encoded subtype adw4. One Nicaraguan strain encoded subtype ayw4, which represented the first report of this subtype within genotype F. Noteworthy, the two subgrupes of genotype F strains correlated with the amino acid substitution at position 45, which were Thr and Leu for the Central American and South American subgroups, respectively. The presence of pre-core stop mutations was investigated in 19 HBV strains derived from anti-HBe positive sera. The mutation A 1896 was found 11 out of 17 genotype F strains. Since the pre-core sequence in published genotype F genomes have C 1858, known to prevent the emergence of the pre-core stop mutation, position 1858 was also examined. All but one of the 17 genotype F strains had T 1858. This substitution was also found in five genotype F strains from HBeAg positive sera. The substitutions at position 1858 were found to strictly correlate with the two mentioned subgroups of genotype F. Analysis of the complete genomes of the divergent Nicaraguan strains and one strain from California also encoding adw4, showed nucleotide divergences from 0.8-2.5 % from each other, 7.2- 10. 1 % from genotype F and 13.2-15.7% from other HBV genotypes. Since pairwise comparisons of 82 complete HBV genomes showed intra and inter-typic nucleotide differences from 0.1-7.1% and 6.8-17.1%, respectively, these three strains were found to represent a new H13V genotype, that was designated H. When comparing the primary structures of the gene products for the three strains with genotype F strains several differences were found, the majority of them in the polymerase region. At phylogenetic analysis of complete genomes and subgenomic regions the three strains always clustered together in a distinct branch from genotype F supported by 100% bootstrap. Apart from Nicaragua and California, this genotype has now also been found in Mexico. The complete genomes were also sequenced for two HBV strains, one from Spain and one from Sweden, classified as genotype D based on their S gene sequences, although encoding d-specificity. The two strains were confirmed to belong to genotype D, and differed from other genotype D strains by 2.8-4.6%. However, their S genes encoded Lys 122, Thr 127 and Arg 160, corresponding to the putative new subtype adw3. This is also the first report on strains encoding d-specificity within genotype D known to encode ayw2, ayw3 and rarely ayw4. In conclusion HAV strains circulating in CA were found to belong to the worldwide-distributed genotype IA. Limited sequencing within the VP1 region proved useful to identify common source outbreaks of hepatitis A also in this highly endemic area, where most strains are local and only one subtype prevails. We also found that the Amerindian genotype F of HBV predominates among Central American populations of Hispanic background, and that it may carry the pre-core stop mutant, which was not anticipated considering previously available sequence information. A new HBV genotype, designated H, was found in CA, also known to be present in Mexico and the California. Genotype H was most similar to F and has most likely both split off from the common ancestor within the New World.
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10.
  • Barack, Leor, et al. (författare)
  • Black holes, gravitational waves and fundamental physics : a roadmap
  • 2019
  • Ingår i: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 36:14
  • Forskningsöversikt (refereegranskat)abstract
    • The grand challenges of contemporary fundamental physics dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
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11.
  • Bosmans, Kim, et al. (författare)
  • Experiences of insecurity among non-standard workers across different welfare states : A qualitative cross-country study
  • 2023
  • Ingår i: Social Science and Medicine. - : Elsevier. - 0277-9536 .- 1873-5347. ; 327
  • Tidskriftsartikel (refereegranskat)abstract
    • In recent decades, economic crises and political reforms focused on employment flexibilization have increased the use of non-standard employment (NSE). National political and economic contexts determine how employers interact with labour and how the state interacts with labour markets and manages social welfare policies. These factors influence the prevalence of NSE and the level of employment insecurity it creates, but the extent to which a country’s policy context mitigates the health influences of NSE is unclear. This study describes how workers experience insecurities created by NSE, and how this influences their health and well-being, in countries with different welfare states: Belgium, Canada, Chile, Spain, Sweden, and the United States. Interviews with 250 workers in NSE were analysed using a multiple-case study approach. Workers in all countries experienced multiple insecurities (e.g., income and employment insecurity) and relational tension with employers/clients, with negative health and well-being influences, in ways that were shaped by social inequalities (e.g., related to family support or immigration status). Welfare state differences were reflected in the level of workers’ exclusion from social protections, the time scale of their insecurity (threatening daily survival or longer-term life planning), and their ability to derive a sense of control from NSE. Workers in Belgium, Sweden, and Spain, countries with more generous welfare states, navigated these insecurities with greater success and with less influence on health and well-being. Findings contribute to our understanding of the health and well-being influences of NSE across different welfare regimes and suggest the need in all six countries for stronger state responses to NSE. Increased investment in universal and more equal rights and benefits in NSE could reduce the widening gap between standard and NSE. 
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12.
  • Bouakaze, Caroline, et al. (författare)
  • Predicting haplogroups using a versatile machine learning program (PredYMaLe) on a new mutationally balanced 32 Y-STR multiplex (CombYplex) : Unlocking the full potential of the human STR mutation rate spectrum to estimate forensic parameters
  • 2020
  • Ingår i: Forensic Science International. - : Elsevier BV. - 1872-4973 .- 1878-0326. ; 48
  • Tidskriftsartikel (refereegranskat)abstract
    • We developed a new mutationally well-balanced 32 Y-STR multiplex (CombYplex) together with a machine learning (ML) program PredYMaLe to assess the impact of STR mutability on haplogourp prediction, while respecting forensic community criteria (high DC/HD). We designed CombYplex around two sub-panels M1 and M2 characterized by average and high-mutation STR panels. Using these two sub-panels, we tested how our program PredYmale reacts to mutability when considering basal branches and, moving down, terminal branches. We tested first the discrimination capacity of CombYplex on 996 human samples using various forensic and statistical parameters and showed that its resolution is sufficient to separate haplogroup classes. In parallel, PredYMaLe was designed and used to test whether a ML approach can predict haplogroup classes from Y-STR profiles. Applied to our kit, SVM and Random Forest classifiers perform very well (average 97 %), better than Neural Network (average 91 %) and Bayesian methods (< 90 %). We observe heterogeneity in haplogroup assignation accuracy among classes, with most haplogroups having high prediction scores (99-100 %) and two (E1b1b and G) having lower scores (67 %). The small sample sizes of these classes explain the high tendency to misclassify the Y-profiles of these haplogroups; results were measurably improved as soon as more training data were added. We provide evidence that our ML approach is a robust method to accurately predict haplogroups when it is combined with a sufficient number of markers, well-balanced mutation rate Y-STR panels, and large ML training sets. Further research on confounding factors (such as CNV-STR or gene conversion) and ideal STR panels in regard to the branches analysed can be developed to help classifiers further optimize prediction scores.
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13.
  • Buselli, Irene, et al. (författare)
  • Natural language processing for aviation safety : Extracting knowledge from publicly-available loss of separation reports
  • 2022
  • Ingår i: Open Research Europe. - : F1000 Research Ltd. - 2732-5121. ; , s. 1-39
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The air traffic management (ATM) system has historicallycoped with a global increase in traffic demand ultimately leading toincreased operational complexity.When dealing with the impact of this increasing complexity on systemsafety it is crucial to automatically analyse the losses of separation(LoSs) using tools able to extract meaningful and actionableinformation from safety reports.Current research in this field mainly exploits natural languageprocessing (NLP) to categorise the reports,with the limitations that theconsidered categories need to be manually annotated by experts andthat general taxonomies are seldom exploited.Methods: To address the current gaps,authors propose to performexploratory data analysis on safety reports combining state-of-the-arttechniques like topic modelling and clustering and then to develop analgorithm able to extract the Toolkit for ATM Occurrence Investigation(TOKAI) taxonomy factors from the free-text safety reports based onsyntactic analysis.TOKAI is a tool for investigation developed by EUROCONTROL and itstaxonomy is intended to become a standard and harmonisedapproach to future investigations.Results: Leveraging on the LoS events reported in the publicdatabases of the Comisi n de Estudio y An lisis de Notificaciones deIncidentes de Tr nsito A reo and the United Kingdom AirproxBoard,authors show how their proposal is able to automaticallyextract meaningful and actionable information from safetyreports,other than to classify their content according to the TOKAItaxonomy.The quality of the approach is also indirectly validated by checking theconnection between the identified factors and the main contributor ofthe incidents.Conclusions: Authors' results are a promising first step toward the fullautomation of a general analysis of LoS reports supported by resultson real-world data coming from two different sources.In the future,authors' proposal could be extended to othertaxonomies or tailored to identify factors to be included in the safetytaxonomies.KeywordsATM, Safety, Resilience, Natural Language Processing, Losses ofSeparation, Safety Reports, TOKAI
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14.
  • Bälter, Magnus, 1986, et al. (författare)
  • Reversible Energy-Transfer Switching on a DNA Scaffold
  • 2015
  • Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 137:7, s. 2444-2447
  • Tidskriftsartikel (refereegranskat)abstract
    • We show that FRET between Pacific Blue (PB) and Alexa488 (A488) covalently attached to a DNAscaffold can be reversibly controlled by photochromicswitching of a spiropyran derivative. With the spiropyranin the closed spiro isomeric form, FRET occurs freelybetween PB and A488. UV-induced isomerization to theopen merocyanine form shuts down the FRET process byefficient quenching of the PB excited state. The process isreversed by exposure to visible light, triggering theisomerization to the spiro isomer.
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15.
  • Cabrera-Rode, Eduardo, et al. (författare)
  • An Exploratory Study of Itolizumab on the Preservation of Beta Cell Function in Adults with Recent-Onset Type 1 Diabetes
  • 2022
  • Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 11:7
  • Tidskriftsartikel (refereegranskat)abstract
    • We conducted a phase I-IIa, randomized, monocentric, double-blind, placebo-controlled clinical trial to evaluate the safety and impact of the combination treatment of Itolizumab and insulin on preserving beta cell function in adults with recent-onset type 1 diabetes. Twelve patients were randomly assigned to three treatment groups, each receiving a different Itolizumab dose (0.4/0.8/1.6 mg/kg body weight, respectively) and a placebo group. All patients received concomitant intensive multiple-dose insulin therapy. Endogenous insulin secretion was assessed by the measurement of C-peptide during the mixed-meal tolerance test. No serious adverse events were reported. No changes in the total daily insulin doses, glycated hemoglobin levels, and stimulated C-peptide were observed between the Itolizumab and placebo groups at 52 weeks. A significant decrease in stimulated C-peptide was observed during the follow-up period (p = 0.012). One subject treated with 1.6 mg of Itolizumab showed a marked increase in the levels of stimulated C-peptide three years after completion of the trial. Taken together, this is the first study to demonstrate that combination treatment with Itolizumab and insulin is safe in humans and does not affect the residual function of beta cells up to 52 weeks. The findings from our study show preliminary evidence that high doses of Itolizumab could potentially arrest the loss of beta cell function in the long term. Further studies with a longer follow-up and larger numbers of patients are envisaged to assess the effect with high dose Itolizumab.
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16.
  • Chazdon, Robin L., et al. (författare)
  • Carbon sequestration potential of second-growth forest regeneration in the Latin American tropics
  • 2016
  • Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 2:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Regrowth of tropical secondary forests following complete or nearly complete removal of forest vegetation actively stores carbon in aboveground biomass, partially counterbalancing carbon emissions from deforestation, forest degradation, burning of fossil fuels, and other anthropogenic sources. We estimate the age and spatial extent of lowland second-growth forests in the Latin American tropics and model their potential aboveground carbon accumulation over four decades. Our model shows that, in 2008, second-growth forests (1 to 60 years old) covered 2.4 million km2 of land (28.1% of the total study area). Over 40 years, these lands can potentially accumulate a total aboveground carbon stock of 8.48 Pg C (petagrams of carbon) in aboveground biomass via low-cost natural regeneration or assisted regeneration, corresponding to a total CO2 sequestration of 31.09 Pg CO2. This total is equivalent to carbon emissions from fossil fuel use and industrial processes in all of Latin America and the Caribbean from 1993 to 2014. Ten countries account for 95% of this carbon storage potential, led by Brazil, Colombia, Mexico, and Venezuela. We model future land-use scenarios to guide national carbon mitigation policies. Permitting natural regeneration on 40% of lowland pastures potentially stores an additional 2.0 Pg C over 40 years. Our study provides information and maps to guide national-level forest-based carbon mitigation plans on the basis of estimated rates of natural regeneration and pasture abandonment. Coupled with avoided deforestation and sustainable forest management, natural regeneration of second-growth forests provides a low-cost mechanism that yields a high carbon sequestration potential with multiple benefits for biodiversity and ecosystem services.
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17.
  • Colomé, Núria, et al. (författare)
  • Multi-laboratory experiment PME11 for the standardization of phosphoproteome analysis
  • 2022
  • Ingår i: Journal of Proteomics. - : Elsevier. - 1874-3919 .- 1876-7737. ; 251
  • Tidskriftsartikel (refereegranskat)abstract
    • Global analysis of protein phosphorylation by mass spectrometry proteomic techniques has emerged in the last decades as a powerful tool in biological and biomedical research. However, there are several factors that make the global study of the phosphoproteome more challenging than measuring non-modified proteins. The low stoichiometry of the phosphorylated species and the need to retrieve residue specific information require particular attention on sample preparation, data acquisition and processing to ensure reproducibility, qualitative and quantitative robustness and ample phosphoproteome coverage in phosphoproteomic workflows. Aiming to investigate the effect of different variables in the performance of proteome wide phosphoprotein analysis protocols, ProteoRed-ISCIII and EuPA launched the Proteomics Multicentric Experiment 11 (PME11). A reference sample consisting of a yeast protein extract spiked in with different amounts of a phosphomix standard (Sigma/Merck) was distributed to 31 laboratories around the globe. Thirty-six datasets from 23 laboratories were analyzed. Our results indicate the suitability of the PME11 reference sample to benchmark and optimize phosphoproteomics strategies, weighing the influence of different factors, as well as to rank intra and inter laboratory performance.
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18.
  • de Escobar, Cícero Coelho, et al. (författare)
  • Molecularly imprinted TiO2 photocatalysts for degradation of diclofenac in water
  • 2018
  • Ingår i: Colloids and Surfaces A: Physicochemical and Engineering Aspects. - : Elsevier BV. - 0927-7757. ; 538, s. 729-738
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to improve the selectivity in photocatalytic process, molecularly imprinted photocatalysts containing a low loading of TiO2 (from 6.6 to 16.6% of total mass) were prepared for photocatalytic degradation of an organic pollutant, diclofenac (DIC). The photocatalytic component TiO2 (P25), with and without being doped with Cu2O, was embedded in diclofenac-imprinted polymers. The molecularly imprinted polymers (MIPs) and the composite photocatalysts exhibited a superior specific target recognition for selective degradation of DIC over non-target reference molecules, fluoxetine (FLU) and paracetamol (PARA). In contrast to the non-selective commercial sample of TiO2, the average value of selectivity of the imprinted catalysts for photocatalytic degradation of DIC was estimated to be 2.8, which suggests that the specific binding sites created by the molecular imprinting are essential for gaining high catalytic selectivity and efficiency. After 6 cycles of testing under UV-light, the imprinted catalysts maintained almost the same efficiency for photo degradation of DIC. In addition, the morphology and the structure of the imprinted catalysts remained after repeated uses. The results suggest that it is feasible to use MIPs to control the selectivity of photocatalytic degradation of organic pollutants.
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19.
  • Demetris, Anthony J, et al. (författare)
  • Liver biopsy interpretation for causes of late liver allograft dysfunction.
  • 2006
  • Ingår i: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 44:2, s. 489-501
  • Tidskriftsartikel (refereegranskat)abstract
    • Evaluation of needle biopsies and extensive clinicopathological correlation play an important role in the determination of liver allograft dysfunction occurring more than 1 year after transplantation. Interpretation of these biopsies can be quite difficult because of the high incidence of recurrent diseases that show histopathological, clinical, and serological features that overlap with each other and with rejection. Also, more than one insult can contribute to allograft injury. In an attempt to enable centers to compare and pool results, improve therapy, and better understand pathophysiological disease mechanisms, the Banff Working Group on Liver Allograft Pathology herein proposes a set of consensus criteria for the most common and problematic causes of late liver allograft dysfunction, including late-onset acute and chronic rejection, recurrent and new-onset viral and autoimmune hepatitis, biliary strictures, and recurrent primary biliary cirrhosis and primary sclerosing cholangitis. A discussion of differential diagnosis is also presented.
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20.
  • Fleming, Cassandra, 1987, et al. (författare)
  • On the use of diarylmaleimide derivatives in biological contexts: An investigation of the photochromic properties in aqueous solution
  • 2017
  • Ingår i: Dyes and Pigments. - : Elsevier BV. - 0143-7208 .- 1873-3743. ; 137, s. 410-420
  • Tidskriftsartikel (refereegranskat)abstract
    • A series of photochromic diarylmaleimide derivatives has been synthesized and studied with respect to the photochromic properties in aqueous solution. The main rationale is to investigate if these compounds could be used as photoswitchable units in biological contexts, motivated by the fact that the diarylmaleimide structural motif is identified in many pharmacophores. Thus, photoswitchable variants of this class of compounds could be very useful in the quest for photoactivatable drugs. The photoinduced cyclization reaction (colorization) is suppressed in solvents of high polarity, whereas the ring-opening reaction (decolorization) still occurs with high efficiency. The photochromically active anti-parallel conformer of the open form is more abundant in the asymmetrically substituted derivatives, which in turn favors the formation of the closed isomeric form. The rates of the thermal isomerization reactions have also been assessed, together with the resistance toward thermal degradation. Here it was observed that the maleimide derived compounds were not susceptible to the thermally driven reactions (hydrolysis and isomerization). (C) 2016 Elsevier Ltd. All rights reserved.
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21.
  • Forouzanfar, Mohammad H, et al. (författare)
  • Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
  • 2015
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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22.
  • Gutierrez-Gutierrez, Belen, et al. (författare)
  • Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients
  • 2021
  • Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 65:11
  • Tidskriftsartikel (refereegranskat)abstract
    • There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.
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23.
  • Hacke, Moritz, et al. (författare)
  • Inhibition of Ebola virus glycoprotein-mediated cytotoxicity by targeting its transmembrane domain and cholesterol
  • 2015
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • The high pathogenicity of the Ebola virus reflects multiple concurrent processes on infection. Among other important determinants, Ebola fusogenic glycoprotein (GP) has been associated with the detachment of infected cells and eventually leads to vascular leakage and haemorrhagic fever. Here we report that the membrane-anchored GP is sufficient to induce the detachment of adherent cells. The results show that the detachment induced through either full-length GP(1,2) or the subunit GP(2) depends on cholesterol and the structure of the transmembrane domain. These data reveal a novel molecular mechanism in which GP regulates Ebola virus assembly and suggest that cholesterol-reducing agents could be useful as therapeutics to counteract GP-mediated cell detachment.
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24.
  •  
25.
  • Lederman, Judith S., et al. (författare)
  • Completing the progression establishing an international baseline of primary, middle and secondary students’ views of scientific inquiry
  • 2023
  • Ingår i: International Journal of Science Education. - : Routledge. - 0950-0693 .- 1464-5289.
  • Tidskriftsartikel (refereegranskat)abstract
    • Knowledge of scientific inquiry (SI) is considered essential to the development of an individual's Scientific Literacy (SL) and therefore, SI is included in many international science education reform documents. Two previous large scale international studies assessed the SI understandings of students entering middle school and secondary students at the end of their formal K-12 science education. The purpose of this international project was to use the VASI-E to collect data on what primary level students have learned about SI in their first few years of school. This study adds to previous research to bridge the landscape of SI understandings now with representation from primary, middle and high school samples. A total of 4,238 students from 35 countries/regions spanning six continents participated in the study. The results show that globally, primary students are not adequately informed about SI for their age group. However, when compared with the students in the previous international studies (grades seven and 12), the primary students' understandings were surprisingly closer to the levels of understanding of SI of the secondary school students than those in the seventh grade study.
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26.
  • Mansouri, Kamel, et al. (författare)
  • CoMPARA : Collaborative Modeling Project for Androgen Receptor Activity
  • 2020
  • Ingår i: Journal of Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 128:2, s. 1-17
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Endocrine disrupting chemicals (EDCs) are xenobiotics that mimic the interaction of natural hormones and alter synthesis, transport, or metabolic pathways. The prospect of EDCs causing adverse health effects in humans and wildlife has led to the development of scientific and regulatory approaches for evaluating bioactivity. This need is being addressed using high-throughput screening (HTS) in vitro approaches and computational modeling.OBJECTIVES: In support of the Endocrine Disruptor Screening Program, the U.S. Environmental Protection Agency (EPA) led two worldwide consortiums to virtually screen chemicals for their potential estrogenic and androgenic activities. Here, we describe the Collaborative Modeling Project for Androgen Receptor Activity (CoMPARA) efforts, which follows the steps of the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP).METHODS: The CoMPARA list of screened chemicals built on CERAPP's list of 32,464 chemicals to include additional chemicals of interest, as well as simulated ToxCast (TM) metabolites, totaling 55,450 chemical structures. Computational toxicology scientists from 25 international groups contributed 91 predictive models for binding, agonist, and antagonist activity predictions. Models were underpinned by a common training set of 1,746 chemicals compiled from a combined data set of 11 ToxCast (TM)/Tox21 HTS in vitro assays.RESULTS: The resulting models were evaluated using curated literature data extracted from different sources. To overcome the limitations of single-model approaches, CoMPARA predictions were combined into consensus models that provided averaged predictive accuracy of approximately 80% for the evaluation set.DISCUSSION: The strengths and limitations of the consensus predictions were discussed with example chemicals; then, the models were implemented into the free and open-source OPERA application to enable screening of new chemicals with a defined applicability domain and accuracy assessment. This implementation was used to screen the entire EPA DSSTox database of similar to 875,000 chemicals, and their predicted AR activities have been made available on the EPA CompTox Chemicals dashboard and National Toxicology Program's Integrated Chemical Environment.
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27.
  • Monzó, Patricia, et al. (författare)
  • A novel numerical approach for imposing a temperature boundary condition at the borehole wall in borehole fields
  • 2015
  • Ingår i: Geothermics. - : Elsevier BV. - 0375-6505 .- 1879-3576. ; 56, s. 35-44
  • Tidskriftsartikel (refereegranskat)abstract
    • The design of a borehole field should be based on a long-term simulation of its thermal response for the intended energy loads. A well-known method to evaluate the response is based on a pre-calculated dimensionless function, the g-function. When calculating g-functions, there are two commonly used approaches for treating the boundary condition at the borehole wall: a constant heat flux at every instant of time, or a uniform temperature at a constant total heat flow to the borehole field. This paper is focused on a new approach to model the thermal process of borehole fields; in particular with a precise representation of a uniform temperature boundary condition at the borehole wall. The main purpose of this model is to be used as a research tool to either generate g-functions for particular cases or handle situations that cannot be addressed by others methods. First, the almost constant temperature along the borehole heat exchanger in operation requires a boundary condition of essentially isothermal boreholes along the depth. In a common case, the borehole heat exchangers are connected in parallel, thus all boreholes should have the same temperature. Also, the total heat flow to the borehole field should be constant over time. For this purpose, a numerical model in which the boreholes are filled with a hypothetical highly conductive material has been built, reproducing the isothermal condition. By thermally interconnecting the boreholes, the equal temperature condition is satisfied. Finally, the specified total heat flow is fed into one spot at the highly conductive material. The model is validated by generating g-functions of some simple borehole field configurations. The g-functions present, in general, a good agreement with the existing solutions for a similar boundary condition. Moreover, the model is also tested against real experimental data from a 2. ×. 3 borehole field at an office building. The simulated daily fluid temperatures are compared with measured daily fluid temperatures for the sixth year of operation. The simulated values present, in general, a good agreement with the measured data. The results show that there are no significant differences with regard to the boundary conditions at the borehole wall, which for this specific case is due to the fact that the system is thermally balanced.
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28.
  • Monzó, Patricia, et al. (författare)
  • Experimental Validation of a Numerical Model for the Thermal Response of a Borehole Field
  • 2014
  • Ingår i: ASHRAE TRANSACTIONS 2014, VOL 120, PT 2. - : ASHRAE.
  • Konferensbidrag (refereegranskat)abstract
    • The design of borehole fields for ground coupled-heat pump systems is often based on so-called g-functions, a pre-calculated dimensionless temperature response to a step heat load. The g-function is specific to the borehole field geometry. For a long-term analysis of a particular borehole field, the average borehole wall temperature is obtained from the g-function and a temporal superposition of its thermal load steps. There are two accepted provisions for the g-function regarding the boundary condition used at (and along) the borehole wall: a constant heat flux at every instant of time, or a uniform temperature at constant total heat flow to the borehole field, respectively. In this paper, a numerical model is built up according to the geometrical characteristics and ground thermal properties of a 2x3 borehole demo site at the Universitat Politecnica de Valencia, Spain. The model is separately studied with regard to the two boundary conditions. The models are first compared in terms of their g-function, which are verified against reference solutions. Then, the daily fluid temperatures are obtained from each of these models with measured daily loads during a six year period. The results are compared with measured daily fluid temperatures for the sixth year of operation. The simulated values present, in general, a good agreement with the measured data. The results show that there are no significant differences with regard to the boundary conditions at the borehole wall, which for this specific case is due to the fact that the system is thermally balanced. The simulated temperatures are more accurate during cooling periods.
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29.
  • Naghavi, Mohsen, et al. (författare)
  • Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
  • 2015
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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30.
  • Nordberg, Gunnar F, et al. (författare)
  • Interactions and Mixtures in Metal Toxicology
  • 2015. - 4
  • Ingår i: Handbook on the Toxicology of Metals. - : Academic Press. - 9780123982926 ; , s. 213-238
  • Bokkapitel (refereegranskat)abstract
    • Human exposures to metals, metalloids, and their compounds frequently occur as mixtures, and hence it is important to consider the joint action of these elements in terms of both mechanisms of action and risk assessment purposes. The joint action of these elements may produce additive, synergistic/potentiating, or antagonistic effects that may be manifested as direct cellular toxicity (necrosis or apoptosis) or carcinogenicity. Dose-response relationships may be further influenced by constitutive factors such as age, sex, and the expression of specific proteins. Mechanisms of importance for the development of potentiated or antagonistic toxicity are the expression of metal-binding proteins (metallothioneins or lead-binding proteins) and interference with metal transporters such as DMT-1 and ZIP. Compared to men, women of childbearing age absorb more Cd from the gastrointestinal tract because they have lower iron stores than men. Another example of synergism that occurs in humans is the one between inorganic arsenic and cadmium in inducing kidney toxicity. In many cases, however, direct primary data on the joint action of toxic or essential elements are lacking, and so innovative derivative methods such as the binary weight-of-evidence method have been used to predict potential interactions among groups of metals and metalloids. At present, there is much to be learned about the joint action of both toxic and essential elements, and this is clearly a critical area of research.
  •  
31.
  • Nordberg, Gunnar F., et al. (författare)
  • Interactions in Metal Toxicology
  • 2007. - 3
  • Ingår i: Handbook on the Toxicology of Metals, 3rd Edition. - San Diego : Elsevier. - 9780123694133 ; , s. 117-145
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • Human exposures to metals and metalloids such as arsenic frequently occur as mixtures, and hence it is important to consider interactions among these elements in terms of both mechanisms of action and for risk assessment purposes. Interactions among these elements may produce additive, synergistic/potentiative, or antagonistic effects that may be manifested as direct cellular toxicity (necrosis or apoptosis) or carcinogenicity. Dose-response relationships may further be influenced by constitutive factors such as age, sex, and the expression of specific proteins. The roles of molecular factors regulated by specific genes (so called gene-environment interactions) for the expression of metal toxicity are known only to a limited extent for most metals. However, for chronic beryllium disease causing fibrosis of the lung, it has been shown that beryllium sensitization, a prerequisite for developing the disease, depends on an antigen-specific immune response occurring predominantly among persons with a specific HLA-DBP1 genotype. Some gene-environment interactions in terms of genetic polymorphisms have been demonstrated such as those involving ALAD and arsenic methyl transferases, but the importance of these observations for development of human diseases has not been fully explored. Mechanisms of importance for interactions and the development of toxicity are the expression of metal-binding proteins (metallothioneins or lead-binding proteins). In many cases, direct primary data on interactions among toxic or essential elements are lacking, and so innovative derivative methods such as the binary weight of evidence (BINWOE) method have been used to predict potential interactions among groups of metals and metalloids. At present, there is much to be learned about interactions among both toxic and essential elements, but this is clearly a critical area of research.
  •  
32.
  • Otano, Itziar, et al. (författare)
  • CD137 (4-1BB) costimulation of CD8+ T cells is more potent when provided in cis than in trans with respect to CD3-TCR stimulation
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • CD137 (4-1BB; TNFSR9) is an activation-induced surface receptor that through costimulation effects provide antigen-primed T cells with augmented survival, proliferation and effector functions as well as metabolic advantages. These immunobiological mechanisms are being utilised for cancer immunotherapy with agonist CD137-binding and crosslinking-inducing agents that elicit CD137 intracellular signaling. In this study, side-by-side comparisons show that provision of CD137 costimulation in-cis with regard to the TCR-CD3-ligating cell is superior to that provided in-trans in terms of T cell activation, proliferation, survival, cytokine secretion and mitochondrial fitness in mouse and human. Cis ligation of CD137 relative to the TCR-CD3 complex results in more intense canonical and non-canonical NF-κB signaling and provides a more robust induction of cell cycle and DNA damage repair gene expression programs. Here we report that the superiority of cis versus trans CD137-costimulation is readily observed in vivo and is relevant for understanding the immunotherapeutic effects of CAR T cells and CD137 agonistic therapies currently undergoing clinical trials, which may provide costimulation either in cis or in trans.
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33.
  • Oxenstierna, Johan, et al. (författare)
  • Formulation of a Layout-Agnostic Order Batching Problem
  • 2021
  • Ingår i: Optimization and Learning - 4th International Conference, OLA 2021, Proceedings. - Cham : Springer International Publishing. - 1865-0937 .- 1865-0929. - 9783030856717 ; 1443, s. 216-226
  • Konferensbidrag (refereegranskat)abstract
    • To date, research on warehouse order-batching has been limited by reliance on rigid assumptions regarding rack layouts. Although efficient optimization algorithms have been provided for conventional warehouse layouts with Manhattan style blocks of racks, they are limited in that they fail to generalize to unconventional layouts. This paper builds on a generalized procedure for digitization of warehouses where racks and other obstacles are defined using two-dimensional polygons. We extend on this digitization procedure to introduce a layout-agnostic minisum formulation for the Order Batching Problem (OBP), together with a sub-problem for the OBP for a single vehicle, the single batch OBP. An algorithm which optimizes the single batch OBP iteratively until an approximate solution to the OBP can be obtained, is discussed. The formulations will serve as the fundament for further work on layout-agnostic OBP optimization and generation of benchmark datasets. Experimental results for the digitization process involving various settings are presented.
  •  
34.
  • Pais, V. F., et al. (författare)
  • OFF-ON-OFF Fluorescence Switch with T-Latch Function
  • 2011
  • Ingår i: Organic Letters. - : American Chemical Society (ACS). - 1523-7052 .- 1523-7060. ; 13:20, s. 5572-5575
  • Tidskriftsartikel (refereegranskat)abstract
    • A novel molecular system with characteristics of an OFF-ON-OFF fluorescence switch was designed to integrate the function of a T-latch. In detail, a receptor(1)-fluorophore-receptor(2) architecture was adopted to achieve fluorescence switching upon addition of protons.
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35.
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36.
  • Poorter, Lourens, et al. (författare)
  • Wet and dry tropical forests show opposite successional pathways in wood density but converge over time
  • 2019
  • Ingår i: Nature Ecology & Evolution. - : Nature Publishing Group. - 2397-334X. ; 3:6, s. 928-934
  • Tidskriftsartikel (refereegranskat)abstract
    • Tropical forests are converted at an alarming rate for agricultural use and pastureland, but also regrow naturally through secondary succession. For successful forest restoration, it is essential to understand the mechanisms of secondary succession. These mechanisms may vary across forest types, but analyses across broad spatial scales are lacking. Here, we analyse forest recovery using 1,403 plots that differ in age since agricultural abandonment from 50 sites across the Neotropics. We analyse changes in community composition using species-specific stem wood density (WD), which is a key trait for plant growth, survival and forest carbon storage. In wet forest, succession proceeds from low towards high community WD (acquisitive towards conservative trait values), in line with standard successional theory. However, in dry forest, succession proceeds from high towards low community WD (conservative towards acquisitive trait values), probably because high WD reflects drought tolerance in harsh early successional environments. Dry season intensity drives WD recovery by influencing the start and trajectory of succession, resulting in convergence of the community WD over time as vegetation cover builds up. These ecological insights can be used to improve species selection for reforestation. Reforestation species selected to establish a first protective canopy layer should, among other criteria, ideally have a similar WD to the early successional communities that dominate under the prevailing macroclimatic conditions.
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37.
  • Price, Patricia E., et al. (författare)
  • Dressing-related pain in patients with chronic wounds : an international patient perspective
  • 2008
  • Ingår i: International Wound Journal. - 1742-4801 .- 1742-481X. ; 5:2, s. 159-171
  • Tidskriftsartikel (refereegranskat)abstract
    • This cross-sectional international survey assessed patients' perceptions of their wound pain. A total of 2018 patients (57% female) from 15 different countries with a mean age of 68.6 years (SD = 15.4) participated. The wounds were categorised into ten different types with a mean wound duration of 19.6 months (SD = 51.8). For 2018 patients, 3361 dressings/compression systems were being used, with antimicrobials being reported most frequently (n= 605). Frequency of wound-related pain was reported as 32.2%, 'never' or 'rarely', 31.1%, 'quite often' and 36.6%, 'most' or 'all of the time', with venous and arterial ulcers associated with more frequent pain (P= 0.002). All patients reported that 'the wound itself' was the most painful location (n= 1840). When asked if they experienced dressing-related pain, 286 (14.7%) replied 'most of the time' and 334 (17.2%) reported pain 'all of the time'; venous, mixed and arterial ulcers were associated with more frequent pain at dressing change (P < 0.001). Eight hundred and twelve (40.2%) patients reported that it took <1 hour for the pain to subside after a dressing change, for 449 (22.2%) it took 1-2 hours, for 192 (9.5%) it took 3-5 hours and for 154 (7.6%) patients it took more than 5 hours. Pain intensity was measured using a visual analogue scale (VAS) (0-100) giving a mean score of 44.5 (SD = 30.5, n= 1981). Of the 1141 who reported that they generally took pain relief, 21% indicated that they did not feel it was effective. Patients were asked to rate six symptoms associated with living with a chronic wound; 'pain' was given the highest mean score of 3.1 (n= 1898). In terms of different types of daily activities, 'overdoing things' was associated with the highest mean score (mean = 2.6, n= 1916). During the stages of the dressing change procedure; 'touching/handling the wound' was given the highest mean score of 2.9, followed by cleansing and dressing removal (n= 1944). One thousand four hundred and eighty-five (80.15%) patients responded that they liked to be actively involved in their dressing changes, 1141 (58.15%) responded that they were concerned about the long-term side-effects of medication, 790 (40.3%) of patient indicated that the pain at dressing change was the worst part of living with a wound. This study adds substantially to our knowledge of how patients experience wound pain and gives us the opportunity to explore cultural differences in more detail.
  •  
38.
  • Price, Patricia E., et al. (författare)
  • Dressing-related pain in patients with chronic wounds : an international patient perspective
  • 2008
  • Ingår i: International Wound Journal. - : Wiley-Blackwell Publishing Ltd. - 1742-4801 .- 1742-481X. ; 5:2, s. 159-171
  • Tidskriftsartikel (refereegranskat)abstract
    • This cross-sectional international survey assessed patients' perceptions of their wound pain. A total of 2018 patients (57% female) from 15 different countries with a mean age of 68.6 years (SD = 15.4) participated. The wounds were categorised into ten different types with a mean wound duration of 19.6 months (SD = 51.8). For 2018 patients, 3361 dressings/compression systems were being used, with antimicrobials being reported most frequently (n= 605). Frequency of wound-related pain was reported as 32.2%, 'never' or 'rarely', 31.1%, 'quite often' and 36.6%, 'most' or 'all of the time', with venous and arterial ulcers associated with more frequent pain (P= 0.002). All patients reported that 'the wound itself' was the most painful location (n= 1840). When asked if they experienced dressing-related pain, 286 (14.7%) replied 'most of the time' and 334 (17.2%) reported pain 'all of the time'; venous, mixed and arterial ulcers were associated with more frequent pain at dressing change (P < 0.001). Eight hundred andtwelve (40.2%) patients reported that it took <1 hour for the pain to subside after a dressing change, for 449 (22.2%) it took 1-2 hours, for 192 (9.5%) it took 3-5 hours and for 154 (7.6%) patients it took more than 5 hours. Pain intensity was measured using a visual analogue scale (VAS) (0-100) giving a mean score of 44.5 (SD = 30.5, n= 1981). Of the 1141 who reported that they generally took pain relief, 21% indicated that they did not feel it was effective. Patients were asked to rate six symptoms associated with living with a chronic wound; 'pain' was given the highest mean score of 3.1 (n= 1898). In terms of different types of daily activities, 'overdoing things' was associated with the highest mean score (mean = 2.6, n= 1916). During the stages of the dressing change procedure; 'touching/handling the wound' was given the highest mean score of 2.9, followed by cleansing and dressing removal (n= 1944). One thousand four hundred and eighty-five (80.15%) patients responded that they liked to be actively involved in their dressing changes, 1141 (58.15%) responded that they were concerned about the long-term side-effects of medication, 790 (40.3%) of patient indicated that the pain at dressing change was the worst part of living with a wound. This study adds substantially to our knowledge of how patients experience wound pain and gives us the opportunity to explore cultural differences in more detail.
  •  
39.
  • Remón Ruiz, Patricia, 1982, et al. (författare)
  • An acido- and photochromic molecular device that mimics triode action
  • 2016
  • Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1364-548X .- 1359-7345. ; 52:25, s. 4659-4662
  • Tidskriftsartikel (refereegranskat)abstract
    • © The Royal Society of Chemistry 2016. The photo-controlled shift of pH titration curves, describing the acidochromic behaviour of a spiropyran switch network, was harnessed for the realisation of a molecular triode. The intricate network can be correctly interpreted with respect to the pH dependence of the main involved species.
  •  
40.
  • Remón Ruiz, Patricia, 1982, et al. (författare)
  • An All-Photonic Molecule-Based D Flip-Flop
  • 2011
  • Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 133:51, s. 20742-20745
  • Tidskriftsartikel (refereegranskat)abstract
    • The photochromic fluorescence switching of a fulgimide derivative was used to implement the first molecule-based D (delay) flip-flop device, which works based on the principles of sequential logic. The device operates exclusively with photonic signals and can be conveniently switched in repeated cycles. © 2011 American Chemical Society.
  •  
41.
  • Remón Ruiz, Patricia, 1982, et al. (författare)
  • Light-driven control of the composition of a supramolecular network
  • 2019
  • Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1364-548X .- 1359-7345. ; 55:30, s. 4335-4338
  • Tidskriftsartikel (refereegranskat)abstract
    • The composition of a supramolecular network, constituted by several cucurbituril receptors and guests, can be controlled by the reversible and all-photonic switching of a dithienylethene guest.
  •  
42.
  • Remón Ruiz, Patricia, 1982, et al. (författare)
  • Molecular Implementation of Sequential and Reversible Logic Through Photochromic Energy Transfer Switching
  • 2011
  • Ingår i: Chemistry - A European Journal. - : Wiley. - 1521-3765 .- 0947-6539. ; 17:23, s. 6492-6500
  • Tidskriftsartikel (refereegranskat)abstract
    • Photochromic spiropyrans modified with fluorophores were investigated as molecular platforms for the achievement of fluorescence switching through modulation of energy transfer. The dyads were designed in such a way that energy transfer is only observed for the open forms of the photochrome (merocyanine and protonated merocyanine), whereas the closed spiropyran is inactive as an energy acceptor. This was made possible through a deliberate choice of fluorophores (4-amino-1,8-naphthalimide, dansyl, and perylene) that produce zero spectral overlap with the spiro form and considerable overlap for the merocyanine forms. From the Förster theory, energy transfer is predicted to be highly efficient and in some cases of 100 % efficiency. The combined switching by photonic (light of λ>530 nm) and chemical (base) inputs enabled the creation of a sequential logic device, which is the basic element of a keypad lock. Furthermore, in combination with an anthracene-based acidochromic fluorescence switch, a reversible logic device was designed. This enables the unambiguous coding of different input combinations through multicolour fluorescence signalling. All devices can be conveniently reset to their initial states and repeatedly cycled.
  •  
43.
  • Reyes, Yaoska, et al. (författare)
  • Secretor Status Strongly Influences the Incidence of Symptomatic Norovirus Infection in a Genotype-Dependent Manner in a Nicaraguan Birth Cohort
  • 2022
  • Ingår i: Journal of Infectious Diseases. - : OXFORD UNIV PRESS INC. - 0022-1899 .- 1537-6613. ; 225:1, s. 105-115
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. The role of histo-blood group on the burden and severity of norovirus gastroenteritis in young infants has not been well documented. Methods. Norovirus gastroenteritis was assessed in 443 Nicaraguan children followed from birth until 3 years of age. Stool samples were tested for norovirus by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and histo-blood group antigens (HBGAs) were determined by phenotyping of saliva and blood. Hazard ratios and predictors of norovirus acute gastroenteritis (AGE) outcome stratified by HBGA were estimated using Cox proportional hazards models. Results. Of 1353 AGE episodes experienced by children, 229 (17%) tested positive for norovirus with an overall incidence of 21.9/100 child-years. Secretor children were infected as early as 2 months of age and had a higher incidence of norovirus GII compared to nonsecretor children (15.4 vs 4.1/100 child-years, P = .006). Furthermore, all GII.4 AGE episodes occurred in secretor children. Children infected with GI (adjusted odds ratio [aOR], 0.09 [95% confidence interval {CI}, .02-.33]) or non-GII.4 viruses (aOR, 0.2 [95% CI, .07-.6]) were less likely to have severe AGE compared to GII.4-infected children. Conclusions. Secretor status in children strongly influences the incidence of symptomatic norovirus infection in a genogroup or genotype-dependent manner and provides evidence that clinical severity in children depends on norovirus genotypes.
  •  
44.
  • Ruiz-Calvo, Félix, et al. (författare)
  • Coupling short-term (B2G model) and long-term (g-function) models for ground source heat exchanger simulation in TRNSYS. Application in a real installation
  • 2016
  • Ingår i: Applied Thermal Engineering. - : Elsevier. - 1359-4311 .- 1873-5606. ; 105, s. 720-732
  • Tidskriftsartikel (refereegranskat)abstract
    • Ground-source heat pump (GSHP) systems represent one of the most promising techniques for heating and cooling in buildings. These systems use the ground as a heat source/sink, allowing a better efficiency thanks to the low variations of the ground temperature along the seasons. The ground-source heat exchanger (GSHE) then becomes a key component for optimizing the overall performance of the system. Moreover, the short-term response related to the dynamic behaviour of the GSHE is a crucial aspect, especially from a regulation criteria perspective in on/off controlled GSHP systems. In this context, a novel numerical GSHE model has been developed at the Instituto de Ingeniería Energética, Universitat Politècnica de València. Based on the decoupling of the short-term and the long-term response of the GSHE, the novel model allows the use of faster and more precise models on both sides. In particular, the short-term model considered is the B2G model, developed and validated in previous research works conducted at the Instituto de Ingeniería Energética. For the long-term, the g-function model was selected, since it is a previously validated and widely used model, and presents some interesting features that are useful for its combination with the B2G model. The aim of the present paper is to describe the procedure of combining these two models in order to obtain a unique complete GSHE model for both short- and long-term simulation. The resulting model is then validated against experimental data from a real GSHP installation.
  •  
45.
  • Srivastava, Tarak, et al. (författare)
  • Fluid flow shear stress over podocytes is increased in the solitary kidney
  • 2014
  • Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 29:1, s. 65-72
  • Tidskriftsartikel (refereegranskat)abstract
    • Glomerular hyperfiltration is emerging as the key risk factor for progression of chronic kidney disease (CKD). Podocytes are exposed to fluid flow shear stress (FFSS) caused by the flow of ultrafiltrate within Bowmans space. The mechanism of hyperfiltration-induced podocyte injury is not clear. We postulated that glomerular hyperfiltration in solitary kidney increases FFSS over podocytes. Infant SpragueDawley rats at 5 days of age and C57BL/6J 14-week-old adult mice underwent unilateral nephrectomy. Micropuncture and morphological studies were then performed on 20- and 60-day-old rats. FFSS over podocytes in uninephrectomized rats and mice was calculated using the recently published equation by Friedrich et al. which includes the variablesusingle nephron glomerular filtration rate (SNGFR), filtration fraction (f), glomerular tuft diameter (2R(T)) and width of Bowmans space (s). Glomerular hypertrophy was observed in uninephrectomized rats and mice. Uninephrectomized rats on Day 20 showed a 2.0-fold increase in SNGFR, 1.0-fold increase in 2R(T) and 2.1-fold increase in FFSS, and on Day 60 showed a 1.9-fold increase in SNGFR, 1.3-fold increase in 2R(T) and 1.5-fold increase in FFSS, at all values of modeled s. Similarly, uninephrectomized mice showed a 2- to 3-fold increase in FFSS at all values of modeled SNGFR. FFSS over podocytes is increased in solitary kidneys in both infant rats and adult mice. This increase is a consequence of increased SNGFR. We speculate that increased FFSS caused by reduced nephron number contributes to podocyte injury and promotes the progression of CKD.
  •  
46.
  • Stratoulias, Vassilis, et al. (författare)
  • ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain
  • 2023
  • Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 26:6, s. 1008-1020
  • Tidskriftsartikel (refereegranskat)abstract
    • Molecular diversity of microglia, the resident immune cells in the CNS, is reported. Whether microglial subsets characterized by the expression of specific proteins constitute subtypes with distinct functions has not been fully elucidated. Here we describe a microglial subtype expressing the enzyme arginase-1 (ARG1; that is, ARG1+ microglia) that is found predominantly in the basal forebrain and ventral striatum during early postnatal mouse development. ARG1+ microglia are enriched in phagocytic inclusions and exhibit a distinct molecular signature, including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3 and Mgl2, compared to ARG1- microglia. Microglial-specific knockdown of Arg1 results in deficient cholinergic innervation and impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, which in turn results in impaired long-term potentiation and cognitive behavioral deficiencies in female mice. Our results expand on microglia diversity and provide insights into microglia subtype-specific functions.
  •  
47.
  • Tse, Quincy, et al. (författare)
  • Interference-Aware Geocasting for VANET
  • 2012
  • Ingår i: WoWMoM.
  • Konferensbidrag (refereegranskat)abstract
    • With the introduction of standards such as DSRC and WAVE, vehicular ad hoc networks (VANET) are being considered as candidates to improve road safety. Safety applications developed on top of VANET enable vehicle and driver improved awareness of the road situation through vehicles sharing their status and knowledge of the road conditions. In order for these systems to operate, they depend on reliable communication. To overcome fading, shadowing and other effects that cause packet loss, such applications commonly use retransmission schemes to improve packet delivery. However, the wireless channels used for these applications are bandwidth constrained, and retransmission can cause interference which in turn will degrade the reliability of the communication channel. Therefore, it is necessary to find a strategy that balances retransmission with channel occupancy for optimal reliability. In this paper, we present a cooperative retransmission algorithm that overcomes shadowing caused by blocking objects such as heavy vehicles in order to combat the resulting unreliability, whilst controlling the interference caused by retransmissions. The proposed algorithm weighs up the additional area a node can cover, with the amount of interference a retransmission by the same node would cause. We evaluate the performance of the algorithm in urban scenarios using the NS-3 simulator, and find that the proposed algorithm is effective in overcoming the negative effects of shadows caused by blocking objects.
  •  
48.
  • Van de Veire, Sara, et al. (författare)
  • Further pharmacological and genetic evidence for the efficacy of PlGF inhibition in cancer and eye disease
  • 2010
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 141:1, s. 178-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Our findings that PlGF is a cancer target and anti-PlGF is useful for anticancer treatment have been challenged by Bais et al. Here we take advantage of carcinogen-induced and transgenic tumor models as well as ocular neovascularization to report further evidence in support of our original findings of PlGF as a promising target for anticancer therapies. We present evidence for the efficacy of additional anti-PlGF antibodies and their ability to phenocopy genetic deficiency or silencing of PlGF in cancer and ocular disease but also show that not all anti-PlGF antibodies are effective. We also provide additional evidence for the specificity of our anti-PlGF antibody and experiments to suggest that anti-PlGF treatment will not be effective for all tumors and why. Further, we show that PlGF blockage inhibits vessel abnormalization rather than density in certain tumors while enhancing VEGF-targeted inhibition in ocular disease. Our findings warrant further testing of anti-PlGF therapies.
  •  
49.
  • Villa, Luisa L., et al. (författare)
  • Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions
  • 2007
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 356:19, s. 1915-1927
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV-16 and HPV-18. METHODS: In this randomized, double-blind trial, we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo, administered at day 1, month 2, and month 6. The primary analysis was performed for a per-protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose (month 7). The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer related to HPV-16 or HPV-18. RESULTS: Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo. Vaccine efficacy for the prevention of the primary composite end point was 98% (95.89% confidence interval [CI], 86 to 100) in the per-protocol susceptible population and 44% (95% CI, 26 to 58) in an intention-to-treat population of all women who had undergone randomization (those with or without previous infection). The estimated vaccine efficacy against all high-grade cervical lesions, regardless of causal HPV type, in this intention-to-treat population was 17% (95% CI, 1 to 31). CONCLUSIONS: In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group.
  •  
50.
  • Vos, Theo, et al. (författare)
  • Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
  • 2015
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 386:9995, s. 743-800
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
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