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Sökning: WFRF:(Lopez Beatriz)

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1.
  • Carraminana, Albert, et al. (författare)
  • Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV)
  • 2019
  • Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : W B SAUNDERS CO-ELSEVIER INC. - 1053-0770 .- 1532-8422. ; 33:9, s. 2492-2502
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. Design: International, multicenter, prospective, randomized controlled clinical trial. Setting: A network of university hospitals. Participants: The study comprises 1,380 patients scheduled for thoracic surgery. Interventions: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. Measurements and Main Results: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients. (C) 2019 Published by Elsevier Inc.
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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.
  • Kassebaum, Nicholas J., et al. (författare)
  • Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
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5.
  • Kehoe, Laura, et al. (författare)
  • Make EU trade with Brazil sustainable
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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6.
  • Allende, Ana, et al. (författare)
  • Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 2: Aminoglycosides/aminocyclitols: apramycin, paromomycin, neomycin and spectinomycin
  • 2021
  • Ingår i: EFSA Journal. - : Wiley. - 1831-4732. ; 19:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The specific concentrations of apramycin, paromomycin, neomycin and spectinomycin in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield, were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC for these antimicrobials, it was not possible to conclude the assessment until further experimental data become available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels in feed that showed to have an effect on growth promotion/increased yield were reported for apramycin and neomycin, whilst for paromomycin and spectinomycin, no suitable data for the assessment were available. It was recommended to carry out studies to generate the data that are required to fill the gaps which prevented the calculation of the FARSC for these four antimicrobials.
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7.
  • Koutso111umanis, Konstantinos, et al. (författare)
  • Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 4: β-Lactams: amoxicillin and penicillin V
  • 2021
  • Ingår i: EFSA Journal. - : Wiley. - 1831-4732. ; 19:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The specific concentrations of amoxicillin and penicillin V in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC, it was not possible to conclude the assessment until further experimental data become available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels in feed that showed to have an effect on growth promotion/increased yield were reported for amoxicillin, whilst for penicillin V no suitable data for the assessment were available. It was recommended to carry out studies to generate the data that are required to fill the gaps which prevented the calculation of the FARSC for these two antimicrobials.
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8.
  • Koutsoumanis, Konstantinos, et al. (författare)
  • Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 1: Methodology, general data gaps and uncertainties
  • 2021
  • Ingår i: EFSA Journal. - : Wiley. - 1831-4732. ; 19:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Commission requested EFSA to assess, in collaboration with EMA, the specific concentrations of antimicrobials resulting from cross-contamination in non-target feed for food-producing animals below which there would not be an effect on the emergence of, and/or selection for, resistance in microbial agents relevant for human and animal health, as well as the levels of the antimicrobials which could have a growth promotion/increase yield effect. The assessment was performed for 24 antimicrobial active substances, as specified in the mandate. This scientific opinion describes the methodology used, and the main associated data gaps and uncertainties. To estimate the antimicrobial levels in the non-target feed that would not result in emergence of, and/or selection for, resistance, a model was developed. This ‘Feed Antimicrobial Resistance Selection Concentration’ (FARSC) model is based on the minimal selective concentration (MSC), or the predicted MSC (PMSC) if MSC for the most susceptible bacterial species is unavailable, the fraction of antimicrobial dose available for exposure to microorganisms in the large intestine or rumen (considering pharmacokinetic parameters), the daily faecal output or rumen volume and the daily feed intake. Currently, lack of data prevents the establishment of PMSC and/or FARSC for several antimicrobials and animal species. To address growth promotion, data from an extensive literature search were used. Specific assessments of the different substances grouped by antimicrobial classes are addressed in separate scientific opinions. General conclusions and recommendations were made.
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9.
  • Koutsoumanis, Konstantinos, et al. (författare)
  • Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 10: Quinolones: flumequine and oxolinic acid
  • 2021
  • Ingår i: EFSA Journal. - : Wiley. - 1831-4732. ; 19:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The specific concentrations of flumequine and oxolinic acid in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC, it was not possible to conclude the assessment until further experimental data are available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. No suitable data for the assessment were available. It was recommended to carry out studies to generate the data that are required to fill the gaps which prevented the calculation of the FARSC for these antimicrobials.
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10.
  • Koutsoumanis, Konstantinos, et al. (författare)
  • Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 11: Sulfonamides
  • 2021
  • Ingår i: EFSA Journal. - : Wiley. - 1831-4732. ; 19:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The specific concentrations of sulfonamides in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC, it was not possible to conclude the assessment until further experimental data are available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels in feed that showed to have an effect on growth promotion/increased yield were identified for three sulfonamides: sulfamethazine, sulfathiazole and sulfamerazine. It was recommended to carry out studies to generate the data that are required to fill the gaps which prevented the calculation of the FARSC for these antimicrobials.
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11.
  • Koutsoumanis, Konstantinos, et al. (författare)
  • Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 12: Tetracyclines: tetracycline, chlortetracycline, oxytetracycline, and doxycycline
  • 2021
  • Ingår i: EFSA Journal. - : Wiley. - 1831-4732. ; 19:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The specific concentrations of tetracycline, chlortetracycline, oxytetracycline and doxycycline in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. The FARSC for these four tetracyclines was estimated. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels in feed that showed to have an effect on growth promotion/increased yield were reported for tetracycline, chlortetracycline, oxytetracycline, whilst for doxycycline no suitable data for the assessment were available. Uncertainties and data gaps associated with the levels reported were addressed. It was recommended to perform further studies to supply more diverse and complete data related to the requirements for calculation of the FARSC for these antimicrobials.
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12.
  • Koutsoumanis, Konstantinos, et al. (författare)
  • Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 13: Diaminopyrimidines: trimethoprim
  • 2021
  • Ingår i: EFSA Journal. - : Wiley. - 1831-4732. ; 19:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The specific concentrations of trimethoprim in non-target feed for food-producing animals below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. The FARSC for trimethoprim was estimated. Uncertainties and data gaps associated to the levels reported were addressed. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. No suitable data for the assessment were available. It was recommended to perform further studies to supply more diverse and complete data related to the requirements for calculation of the FARSC for trimethoprim.
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13.
  • Koutsoumanis, Konstantinos, et al. (författare)
  • Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 3: Amprolium
  • 2021
  • Ingår i: EFSA Journal. - : Wiley. - 1831-4732. ; 19:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The specific concentrations of amprolium in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC for amprolium, it was not possible to conclude the assessment. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels of amprolium in feed that showed to have an effect on growth promotion/increased yield were reported. The lack of antibacterial activity at clinically relevant concentrations for amprolium suggests that further studies relating to bacterial resistance are not a priority.
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14.
  • Koutsoumanis, Konstantinos, et al. (författare)
  • Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 5: Lincosamides: lincomycin
  • 2021
  • Ingår i: EFSA Journal. - : Wiley. - 1831-4732. ; 19:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The specific concentrations of lincomycin in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC, it was not possible to conclude the assessment until further experimental data become available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels of lincomycin in feed that showed to have an effect on growth promotion/increased yield were reported. It was recommended to carry out studies to generate the data that are required to fill the gaps which prevented the calculation of the FARSC for lincomycin.
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15.
  • Koutsoumanis, Konstantinos, et al. (författare)
  • Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 6: Macrolides: tilmicosin, tylosin and tylvalosin
  • 2021
  • Ingår i: EFSA Journal. - : Wiley. - 1831-4732. ; 19:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The specific concentrations of tilmicosin, tylosin and tylvalosin in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield, were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC, it was not possible to conclude the assessment until further experimental data become available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels in feed that showed to have an effect on growth promotion/increased yield were reported for tilmicosin and tylosin, whilst for tylvalosin no suitable data for the assessment were available. It was recommended to carry out studies to generate the data that are required to fill the gaps which prevented the calculation of the FARSC for these three antimicrobials.
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16.
  • Koutsoumanis, Konstantinos, et al. (författare)
  • Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 7: Amphenicols: florfenicol and thiamphenicol
  • 2021
  • Ingår i: EFSA Journal. - : Wiley. - 1831-4732. ; 19:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The specific concentrations of florfenicol and thiamphenicol in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield, were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. The FARSC for florfenicol was estimated. However, due to the lack of data, the calculation of the FARSC for thiamphenicol was not possible until further experimental data become available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels in feed that showed to have an effect on growth promotion/increased yield were reported for florfenicol, whilst for thiamphenicol no suitable data for the assessment were available. Uncertainties and data gaps associated to the levels reported were addressed. For florfenicol, it was recommended to perform further studies to supply more diverse and complete data related to the requirements for calculation of the FARSC, whereas for thiamphenicol, the recommendation was to generate the data required to fill the gaps which prevented the FARSC calculation.
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17.
  • Koutsoumanis, Konstantinos, et al. (författare)
  • Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 8: Pleuromutilins: tiamulin and valnemulin
  • 2021
  • Ingår i: EFSA Journal. - : Wiley. - 1831-4732. ; 19:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The specific concentrations of tiamulin and valnemulin in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC, it was not possible to conclude the assessment until further experimental data become available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels in feed that showed to have an effect on growth promotion/increased yield were reported for tiamulin, while for valnemulin no suitable data for the assessment were available. It was recommended to carry out studies to generate the data that are required to fill the gaps which prevented the calculation of the FARSC for these two antimicrobials.
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18.
  • Koutsoumanis, Konstantinos, et al. (författare)
  • Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 9: Polymyxins: colistin
  • 2021
  • Ingår i: EFSA Journal. - : Wiley. - 1831-4732. ; 19:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The specific concentrations of colistin in non-target feed for food-producing animals, below which there would not be an effect on the emergence of, and/or selection for, resistance in bacteria relevant for human and animal health, as well as the specific antimicrobial concentrations in feed which have an effect in terms of growth promotion/increased yield were assessed by EFSA in collaboration with EMA. Details of the methodology used for this assessment, associated data gaps and uncertainties, are presented in a separate document. To address antimicrobial resistance, the Feed Antimicrobial Resistance Selection Concentration (FARSC) model developed specifically for the assessment was applied. However, due to the lack of data on the parameters required to calculate the FARSC, it was not possible to conclude the assessment until further experimental data become available. To address growth promotion, data from scientific publications obtained from an extensive literature review were used. Levels of colistin in feed that showed to have an effect on growth promotion/increased yield were reported. It was recommended to carry out studies to generate the data that are required to fill the gaps which prevented the calculation of the FARSC for these antimicrobials.
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19.
  • Wang, Haidong, et al. (författare)
  • Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015.
  • 2016
  • Ingår i: The lancet. HIV. - : Elsevier. - 2352-3018. ; 3:8, s. e361-e387
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.METHODS: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.FINDINGS: Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.INTERPRETATION: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.
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20.
  • Wang, Haidong, et al. (författare)
  • Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
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21.
  • Del Cura-González, Isabel, et al. (författare)
  • How to Improve Healthcare for Patients with Multimorbidity and Polypharmacy in Primary Care : A Pragmatic Cluster-Randomized Clinical Trial of the MULTIPAP Intervention
  • 2022
  • Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 12:5
  • Tidskriftsartikel (refereegranskat)abstract
    • (1) Purpose: To investigate a complex MULTIPAP intervention that implements the Ariadne principles in a primary care population of young-elderly patients with multimorbidity and polypharmacy and to evaluate its effectiveness for improving the appropriateness of prescriptions. (2) Methods: A pragmatic cluster-randomized clinical trial was conducted involving 38 family practices in Spain. Patients aged 65-74 years with multimorbidity and polypharmacy were recruited. Family physicians (FPs) were randomly allocated to continue usual care or to provide the MULTIPAP intervention based on the Ariadne principles with two components: FP training (eMULTIPAP) and FP patient interviews. The primary outcome was the appropriateness of prescribing, measured as the between-group difference in the mean Medication Appropriateness Index (MAI) score change from the baseline to the 6-month follow-up. The secondary outcomes were quality of life (EQ-5D-5L), patient perceptions of shared decision making (collaboRATE), use of health services, treatment adherence, and incidence of drug adverse events (all at 1 year), using multi-level regression models, with FP as a random effect. (3) Results: We recruited 117 FPs and 593 of their patients. In the intention-to-treat analysis, the between-group difference for the mean MAI score change after a 6-month follow-up was -2.42 (95% CI from -4.27 to -0.59) and, between baseline and a 12-month follow-up was -3.40 (95% CI from -5.45 to -1.34). There were no significant differences in any other secondary outcomes. (4) Conclusions: The MULTIPAP intervention improved medication appropriateness sustainably over the follow-up time. The small magnitude of the effect, however, advises caution in the interpretation of the results given the paucity of evidence for the clinical benefit of the observed change in the MAI.
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22.
  • Feigin, Valery L., et al. (författare)
  • Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016
  • 2019
  • Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:5, s. 459-480
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable).Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.Funding: Bill & Melinda Gates Foundation.
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23.
  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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24.
  • Lopez-Ayala, Pedro, et al. (författare)
  • Novel Criteria for the Observe-Zone of the ESC 0/1 h-hs-cTnT Algorithm
  • 2021
  • Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:10, s. 773-787
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The non-ST-segment-elevation myocardial infarction (NSTEMI) guidelines of the European Society of Cardiology (ESC) recommend a 3h cardiac troponin determination in patients triaged to the observe-zone of the ESC 0/1h-algorithm; however, no specific cutoff for further triage is endorsed. Recently, a specific cutoff for 0/3h high-sensitivity cardiac troponin T (hs-cTnT) change (7 ng/L) was proposed, warranting external validation. METHODS: Patients presenting with acute chest discomfort to the emergency department were prospectively enrolled into an international multicenter diagnostic study. Final diagnoses were centrally adjudicated by 2 independent cardiologists applying the fourth universal definition of myocardial infarction, on the basis of complete cardiac workup, cardiac imaging, and serial hs-cTnT. Hs-cTnT concentrations were measured at presentation, after 1 hour, and after 3 hours. The objective was to externally validate the proposed cutoff, and if necessary, derive and internally as well as externally validate novel 0/3h-criteria for the observe-zone of the ESC 0/1h-hs-cTnT-algorithm in an independent multicenter cohort. RESULTS: Among 2076 eligible patients, application of the ESC 0/1h-hs-cTnT-algorithm triaged 1512 patients (72.8%) to either rule out or rule in NSTEMI, leaving 564 patients (27.2%) in the observe-zone (adjudicated NSTEMI prevalence, 120/564 patients, 21.3%). The suggested 0/3h-hs-cTnT-change of <7 ng/L triaged 517 patients (91.7%) toward rule-out, resulting in a sensitivity of 33.3% (95% CI, 25.5-42.2), missing 80 patients with NSTEMI, and >= 7 ng/L triaged 47 patients toward rule-in (8.3%), resulting in a specificity of 98.4% (95% CI, 96.8-99.2). Novel derived 0/3h-criteria for the observe-zone patients ruled out NSTEMI with a 3h hs-cTnT concentration <15 ng/L and a 0/3h-hs-cTnT absolute change <4 ng/L, triaging 138 patients (25%) toward rule-out, resulting in a sensitivity of 99.2% (95% CI, 96.0-99.9), missing 1 patient with NSTEMI. A 0/3h-hs-cTnT absolute change >= 6 ng/L triaged 63 patients (11.2%) toward rule-in, resulting in a specificity of 98% (95% CI, 96.2-98.9) Thereby, the novel 0/3h-criteria reduced the number of patients in the observe zone by 36%s and the number of type 1 myocardial infarction by 50%. Findings were confirmed in both internal and external validation. CONCLUSIONS: A combination of a 3h-hs-cTnT concentration (<15 ng/L) and a 0/3h absolute change (<4 ng/L) is necessary to safely rule out NSTEMI in patients remaining in the observe-zone of the ESC 0/1h-hs-cTnT-algorithm.
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25.
  • Martinez-Alvarez, Concepcion, et al. (författare)
  • Injection and adhesion palatoplasty : a preliminary study in a canine model
  • 2013
  • Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 183:2, s. 654-662
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Raising mucoperiosteal flaps in traditional palatoplasty impairs mid-facial growth. Hyaluronic acid-based hydrogels have been successfully tested for minimally invasive craniofacial bone generation in vivo as carriers of bone morphogenetic protein-2 (BMP-2). We aimed to develop a novel flapless technique for cleft palate repair by injecting a BMP-2 containing hydrogel. Material and methods: Dog pups with congenital cleft palate were either non-treated (n = 4) or treated with two-flap palatoplasty (n = 6) or with the proposed injection/adhesion technique (n = 5). The experimental approach was to inject a hyaluronic acid-based hydrogel containing hydroxyapatite and BMP-2 subperiosteally at the cleft palate margins of pups aged six weeks. At week ten, a thin strip of the medial edge mucosa was removed and the margins were closed directly. Occlusal photographs and computed tomography (CT) scans were obtained up to week 20. Results: Four weeks after the gel injection the cleft palate margins had reached the midline and engineered bone had enlarged the palatal bones. Removal of the medial edge mucosa and suturing allowed complete closure of the cleft. Compared to traditional palatoplasty, the injection/adhesion technique was easier, and the post-surgical recovery was faster. CT on week 20 revealed some overlapping or "bending" of palatal shelves in the two-flap repair group, which was not observed in the experimental nor control groups. Conclusion: A minimally invasive technique for cleft palate repair upon injectable scaffolds in a dog model of congenital cleft palate is feasible. Results suggest better growth of palatal bones. This represents an attractive clinical alternative to traditional palatoplasty for cleft palate patients.
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26.
  • Martínez-Sánchez, Noelia, et al. (författare)
  • Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance
  • 2017
  • Ingår i: Cell Metabolism. - Cambridge, MA, United States : Cell Press. - 1550-4131 .- 1932-7420. ; 26:1, s. 212-229.e12
  • Tidskriftsartikel (refereegranskat)abstract
    • Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.
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27.
  • Murray, Christopher J. L., et al. (författare)
  • Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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28.
  • Stanaway, Jeffrey D., et al. (författare)
  • Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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29.
  • Thompson, David, et al. (författare)
  • Assessment of measurement-based methods for separating wheel and track contributions to railway rolling noise
  • 2018
  • Ingår i: Applied Acoustics. - : Elsevier. - 0003-682X .- 1872-910X. ; 140, s. 48-62
  • Tidskriftsartikel (refereegranskat)abstract
    • The noise produced during a train pass-by originates from several different sources such as propulsion noise, noise from auxiliary equipment, aerodynamic noise and rolling noise. The rolling noise is radiated by the wheels and the track and is excited by the wheel and rail unevenness, usually referred to as roughness. The current TSI Noise certification method, which must be satisfied by all new mainline trains in Europe, relies on the use of a reference track to quantify the noise from new vehicles. The reference track is defined by an upper limit of the rail roughness and a lower limit of the track decay rate (TDR). However, since neither the rail roughness nor the track radiation can be completely neglected, the result cannot be taken as representing only the vehicle noise and the measurement does not allow separate identification of the noise radiated by wheel and track. It is even likely that further reductions in the limit values for new rolling stock cannot be achieved on current tracks. There is therefore a need for a method to separate the noise into these two components reliably and cheaply. The purpose of the current study is to assess existing and new methods for rolling noise separation. Field tests have been carried out under controlled conditions, allowing the different methods to be compared. The TWINS model is used with measured vibration data to give reference estimates of the wheel and track noise components. Six different methods are then considered that can be used to estimate the track component. It is found that most of these methods can obtain the track component of noise with acceptable accuracy. However, apart from the TWINS model, the wheel noise component could only be estimated directly using three methods and un- fortunately these did not give satisfactory results in the current tests.
  •  
30.
  • 2019
  • Tidskriftsartikel (refereegranskat)
  •  
31.
  • Alajbeg, Ivan, et al. (författare)
  • Intraoralelectrostimulator for xerostomia relief : along-term, multicenter, open-label, uncontrolled, clinical trial
  • 2012
  • Ingår i: Oral surgery, oral medicine, oral pathology and oral radiology. - : Elsevier. - 2212-4403 .- 2212-4411. ; 113:6, s. 773-781
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: A previous sham-controlled multinational study demonstrated the short-term efficacy and safety for xerostomia treatment of an intraoral device that delivers electrostimulation to the lingual nerve. The objective of this study was to test the hypothesis that those beneficial effects would be sustained over an 11-month period. STUDY DESIGN: The device was tested on a mixed sample of 94 patients with xerostomia in an open-label, uncontrolled, prospective multicenter trial. Statutory outcome assessments were done at 5th, 8th, and 11th months and analyzed by multiple comparisons. RESULTS: Improvements achieved at month 5 from baseline were sustained throughout the follow-up period for the primary outcome, xerostomia severity, and the secondary outcomes resting whole salivary flow rate, xerostomia frequency, oral discomfort, and difficulties in speech, swallowing, and sleeping. No significant side effects were detected. CONCLUSIONS: The beneficial effects of a removable intraoral electrostimulating device were sustained for an 11-month period.
  •  
32.
  • Barredo, José I., et al. (författare)
  • Mapping and assessment of forest ecosystems and their services : Applications and guidance for decision making in the framework of MAES
  • 2015
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of this report is to illustrate by means of a series of case studies the implementation of mapping and assessment of forest ecosystem services in different contexts and geographical levels. Methodological aspects, data issues, approaches, limitations, gaps and further steps for improvement are analysed for providing good practices and decision making guidance. The EU initiative on Mappingand Assessment of Ecosystems and their Services (MAES), with the support of all Member States, contributes to improve the knowledge on ecosystem services. MAES is one of the building-block initiatives supporting the EU Biodiversity Strategy to 2020.
  •  
33.
  • Bernal, Ximena E., et al. (författare)
  • Empowering Latina scientists
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
34.
  • Bernardo-Maestro, Beatriz, et al. (författare)
  • Driving the Active Site Incorporation in Zeolitic Materials via the Organic Structure-Directing Agent Through Development of H-Bonds with Hydroxyl Groups
  • 2022
  • Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 28:42
  • Tidskriftsartikel (refereegranskat)abstract
    • (1S,2S)-N-methyl-pseudoephedrine (MPS) was used as organic structure-directing agent (OSDA) for the synthesis of Mg-doped nanoporous aluminophosphates. This molecule displays a particular conformational behavior, where the presence of H-bond donor and acceptor groups provide a rigid conformational space with one asymmetric conformation preferentially occurring. MPS drives the crystallization of Mg-containing AFI materials. Characterization of these materials shows that the OSDA incorporate as protonated species, arranged as head-to-tail monomers. Combination of three-dimensional electron diffraction with high-resolution synchrotron powder X-ray diffraction allowed to locate both the Mg and the organic species. Interestingly, results showed that the spatial incorporation of Mg is driven by the hydroxyl groups of the organic cation through the development of H-bonds with negatively-charged MgO4 tetrahedra. This work demonstrates that H-bond forming groups can be used to drive the spatial incorporation of low-valent dopants within zeolitic frameworks, a highly desired aim in order to control their catalytic activity and selectivity. 
  •  
35.
  • Bjerrum, Lars, et al. (författare)
  • Health Alliance for prudent antibiotic prescribing in patients with respiratory tract infections (HAPPY AUDIT) -impact of a non-randomised multifaceted intervention programme
  • 2011
  • Ingår i: BMC Family Practice. - : Springer Science and Business Media LLC. - 1471-2296. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Excessive use of antibiotics is worldwide the most important reason for development of antimicrobial resistance. As antibiotic resistance may spread across borders, high prevalence countries may serve as a source of bacterial resistance for countries with a low prevalence. Therefore, bacterial resistance is an important issue with a potential serious impact on all countries. Initiatives have been taken to improve the quality of antibiotic prescribing in primary care, but only few studies have been designed to determine the effectiveness of multifaceted strategies across countries with different practice setting. The aim of this study was to evaluate the impact of a multifaceted intervention targeting general practitioners (GPs) and patients in six countries with different health organization and different prevalence of antibiotic resistance. Methods: GPs from two Nordic countries, two Baltic Countries and two Hispano-American countries registered patients with respiratory tract infections (RTIs) in 2008 and 2009. After first registration they received individual prescriber feedback and they were offered an intervention programme that included training courses, clinical guidelines, posters for waiting rooms, patient brochures and access to point of care tests (Strep A and C-Reactive Protein). Antibiotic prescribing rates were compared before and after the intervention. Results: A total of 440 GPs registered 47011 consultations; 24436 before the intervention (2008) and 22575 after the intervention (2009). After the intervention, the GPs significantly reduced the percentage of consultations resulting in an antibiotic prescription. In patients with lower RTI the GPs in Lithuania reduced the prescribing rate by 42%, in Russia by 25%, in Spain by 25%, and in Argentina by 9%. In patients with upper RTIs, the corresponding reductions in the antibiotic prescribing rates were in Lithania 20%, in Russia 15%, in Spain 9%, and in Argentina 5%. Conclusion: A multifaceted intervention programme targeting GPs and patients and focusing on improving diagnostic procedures in patients with RTIs may lead to a marked reduction in antibiotic prescribing. The pragmatic before-after design used may suffer from some limitations and the reduction in antibiotic prescribing could be influenced by factors not related to the intervention.
  •  
36.
  • Bjerrum, Lars, et al. (författare)
  • Health Alliance for Prudent Prescribing, Yield and Use of Antimicrobial Drugs in the Treatment of Respiratory Tract Infections (HAPPY AUDIT)
  • 2010
  • Ingår i: BMC Family Practice. - : Springer Science and Business Media LLC. - 1471-2296. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Excessive and inappropriate use of antibiotics is considered to be the most important reason for development of bacterial resistance to antibiotics. As antibiotic resistance may spread across borders, high prevalence countries may serve as a source of bacterial resistance for countries with a low prevalence. Therefore, bacterial resistance is an important issue with a potential serious impact on all countries. The majority of respiratory tract infections (RTIs) are treated in general practice. Most infections are caused by virus and antibiotics are therefore unlikely to have any clinical benefit. Several intervention initiatives have been taken to reduce the inappropriate use of antibiotics in primary health care, but the effectiveness of these interventions is only modest. Only few studies have been designed to determine the effectiveness of multifaceted strategies in countries with different practice setting. The aim of this study is to evaluate the impact of a multifaceted intervention targeting general practitioners (GPs) and patients in six countries with different prevalence of antibiotic resistance: Two Nordic countries (Denmark and Sweden), two Baltic Countries (Lithuania and Kaliningrad-Russia) and two Hispano-American countries (Spain and Argentina). Methods/Design: HAPPY AUDIT was initiated in 2008 and the project is still ongoing. The project includes 15 partners from 9 countries. GPs participating in HAPPY AUDIT will be audited by the Audit Project Odense (APO) method. The APO method will be used at a multinational level involving GPs from six countries with different cultural background and different organisation of primary health care. Research on the effect of the intervention will be performed by analysing audit registrations carried out before and after the intervention. The intervention includes training courses on management of RTIs, dissemination of clinical guidelines with recommendations for diagnosis and treatment, posters for the waiting room, brochures to patients and implementation of point of care tests (Strep A and CRP) to be used in the GPs'surgeries. To ensure public awareness of the risk of resistant bacteria, media campaigns targeting both professionals and the public will be developed and the results will be published and widely disseminated at a Working Conference hosted by the World Association of Family Doctors (WONCA-Europe) at the end of the project period. Discussion: HAPPY AUDIT is an EU-financed project with the aim of contributing to the battle against antibiotic resistance through quality improvement of GPs' diagnosis and treatment of RTIs through development of intervention programmes targeting GPs, parents of young children and healthy adults. It is hypothesized that the use of multifaceted strategies combining active intervention by GPs will be effective in reducing prescribing of unnecessary antibiotics for RTIs and improving the use of appropriate antibiotics in suspected bacterial infections.
  •  
37.
  • Brynildsrud, Ola B., et al. (författare)
  • Global expansion of Mycobacterium tuberculosis lineage 4 shaped by colonial migration and local adaptation
  • 2018
  • Ingår i: Science Advances. - : AMER ASSOC ADVANCEMENT SCIENCE. - 2375-2548. ; 4:10
  • Tidskriftsartikel (refereegranskat)abstract
    • On the basis of population genomic and phylogeographic analyses of 1669 Mycobacterium tuberculosis lineage 4 (L4) genomes, we find that dispersal of L4 has been completely dominated by historical migrations out of Europe. We demonstrate an intimate temporal relationship between European colonial expansion into Africa and the Americas and the spread of L4 tuberculosis (TB). Markedly, in the age of antibiotics, mutations conferring antimicrobial resistance overwhelmingly emerged locally (at the level of nations), with minimal cross-border transmission of resistance. The latter finding was found to reflect the relatively recent emergence of these mutations, as a similar degree of local restriction was observed for susceptible variants emerging on comparable time scales. The restricted international transmission of drug-resistant TB suggests that containment efforts at the level of individual countries could be successful.
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38.
  • Caronna, Edoardo, et al. (författare)
  • Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world
  • 2024
  • Ingår i: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. - 0022-3050 .- 1468-330X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months. Methods European multicentre, prospective, real-world study, including high-frequency episodic or chronic migraine (CM) patients treated since March 2018 with anti-CGRP MAbs. We defined good and excellent responses as >= 50% and >= 75% reduction in monthly headache days (MHD) at 6 months, respectively. Generalised mixed-effect regression models (GLMMs) were used to identify variables independently associated with treatment response. Results Of the 5818 included patients, 82.3% were females and the median age was 48.0 (40.0-55.0) years. At baseline, the median of MHD was 20.0 (14.0-28.0) days/months and 72.2% had a diagnosis of CM. At 6 months (n=4963), 56.5% (2804/4963) were good responders and 26.7% (1324/4963) were excellent responders. In the GLMM model, older age (1.08 (95% CI 1.02 to 1.15), p=0.016), the presence of unilateral pain (1.39 (95% CI 1.21 to 1.60), p<0.001), the absence of depression (0.840 (95% CI 0.731 to 0.966), p=0.014), less monthly migraine days (0.923 (95% CI 0.862 to 0.989), p=0.023) and lower Migraine Disability Assessment at baseline (0.874 (95% CI 0.819 to 0.932), p<0.001) were predictors of good response (AUC of 0.648 (95% CI 0.616 to 0.680)). These variables were also significant predictors of excellent response (AUC of 0.691 (95% CI 0.651 to 0.731)). Sex was not significant in the GLMM models. Conclusions This is the largest real-world study of migraine patients treated with anti-CGRP MAbs. It provides evidence that higher migraine frequency and greater disability at baseline reduce the likelihood of responding to anti-CGRP MAbs, informing physicians and policy-makers on the need for an earlier treatment in order to offer the best chance of treatment success.
  •  
39.
  • Costello, Eamon, et al. (författare)
  • Assessment of Transversal Skills in STEM : From theory to practice in a large scale research project
  • 2022
  • Ingår i: Society for Information Technology &amp; Teacher Education International Conference. - San Diego, CA, United States : Association for the Advancement of Computing in Education (AACE), Waynesville, NC USA. ; , s. 1026-1033
  • Konferensbidrag (refereegranskat)abstract
    • This paper presents an overview of a large scale research project involving teachers and students across eight European countries and involving eleven partner organizations. The project was focused on helping equip students with key transversal skills and competencies. We used integrated STEM as a site to ground the development of these interdisciplinary ways of thinking, being and doing and digital tools as ways to help teachers deepen and enhance their formative assessment practice. We present here an outline of research conducted to develop a framework for conceptualising integrated STEM skills and their assessment via digital tools. This framework identified a number of core competencies and ways to both design and assess for these skills using digital tools. We also give an account of subsequent professional development with teachers and the piloting of developed teaching methods in schools. The next phase was the conduct of evaluations of our work according to a research methodology which aimed to identify best practices for scalable teaching. Some emergent findings and lessons learned along the way from two countries, Ireland and Sweden, are presented as examples here as we complete the analysis stage of the project. This paper aims to contribute to the conversations around interdisciplinary and integrated STEM skills, how they can be digitally assessed and to give an account of the workings of the associated large scale research project.
  •  
40.
  • Cristóbal, Lara, et al. (författare)
  • Free anterolateral thigh flap and masseter nerve transfer for reconstruction of extensive periauricular defects : Surgical technique and clinical outcomes
  • 2017
  • Ingår i: Microsurgery. - : John Wiley & Sons. - 0738-1085 .- 1098-2752. ; 37:6, s. 479-486
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Radical tumor ablation in the periauricular area often results in extensive soft tissue defects, including facial nerve sacrifice, bone and/or dura defects. Reconstruction of these defects should aim at restoring facial reanimation, wound closure, and facial and neck contours. We present our experience using free anterolateral thigh flap (ALT) in combination with masseter nerve to facial nerve transfer in managing complex defects in the periauricular area.METHODS: Between 2011 and 2015 six patients underwent a combined procedure of ALT flap reconstruction and masseter nerve transfer, to reconstruct extensive, post tumor resection, periauricular defects. The ALT flap was customized according to the defect. For smile restoration, the masseter nerve was transferred to the buccal branch of the facial nerve. If the facial nerve stump was preserved, interposition of nerve grafts to the zygomatic and frontal branches was performed to provide separate eye closure. The outcomes were analyzed by assessing wound closure, contour deformity, symmetry of the face, and facial nerve function.RESULTS: There were no partial or total flap losses. Stable wound closure and adequate volume replacement in the neck was achieved in all cases, as well as good facial tonus and symmetry. The mean follow-up time of clinical outcomes was 16.8 months. Smile restoration was graded as good or excellent in four cases, moderate in one and fair in one.CONCLUSION: Extensive periauricular defects following oncologic resection could be adequately reconstructed in a combined procedure of free ALT flap and masseter nerve transfer to the facial nerve for smile restoration.
  •  
41.
  • Denisova, Evgeniya, et al. (författare)
  • Frequent DPH3 promoter mutations in skin cancers.
  • 2015
  • Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:34, s. 35922-35930
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent reports suggested frequent occurrence of cancer associated somatic mutations within regulatory elements of the genome. Based on initial exome sequencing of 21 melanomas, we report frequent somatic mutations in skin cancers in a bidirectional promoter of diphthamide biosynthesis 3 (DPH3) and oxidoreductase NAD-binding domain containing 1 (OXNAD1) genes. The UV-signature mutations occurred at sites adjacent and within a binding motif for E-twenty six/ternary complex factors (Ets/TCF), at -8 and -9 bp from DPH3 transcription start site. Follow up screening of 586 different skin lesions showed that the DPH3 promoter mutations were present in melanocytic nevi (2/114; 2%), melanoma (30/304; 10%), basal cell carcinoma of skin (BCC; 57/137; 42%) and squamous cell carcinoma of skin (SCC; 12/31; 39%). Reporter assays carried out in one melanoma cell line for DPH3 and OXNAD1 orientations showed statistically significant increased promoter activity due to -8/-9CC > TT tandem mutations; although, no effect of the mutations on DPH3 and OXNAD1 transcription in tumors was observed. The results from this study show occurrence of frequent somatic non-coding mutations adjacent to a pre-existing binding site for Ets transcription factors within the directional promoter of DPH3 and OXNAD1 genes in three major skin cancers. The detected mutations displayed typical UV signature; however, the functionality of the mutations remains to be determined.
  •  
42.
  • Fanti, Kostas A., et al. (författare)
  • Fearlessness as an Underlying Mechanism Leading to Conduct Problems : Testing the INTERFEAR Model in a Community Sample in Spain
  • 2024
  • Ingår i: Children. - : MDPI. - 2227-9067. ; 11:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Conduct problems (CP) in childhood and adolescence have a significant impact on the individual, family, and community. To improve treatment for CP, there is a need to improve the understanding of the developmental pathways leading to CP in boys and girls. Prior research has linked the child's fearlessness and callous-unemotional (CU) traits, as well as experiences of parental warmth and punitive parenting, to CP. However, few studies have tested the interplay of these factors in contributing to future CP development. The present study aimed to test the InterFear model, which suggests that fearlessness in early childhood leads to CP through an indirect pathway involving low positive parenting, high negative/punitive parenting, and callous-unemotional (CU) traits. The sample included 2467 Spanish children (48.1% girls; Mage = 4.25; SD = 0.91), followed up across a five-year period. Besides a direct association between fearlessness in early childhood and future CP, the results found an indirect pathway whereby fearlessness reduces positive parenting and increases punitive parenting, which contributes to the development of CU traits and sets the stage for CP in later childhood. The specific indirect effect from fearlessness to CP via CU traits accounted for most of the variance, suggesting the existence of a temperamental pathway independent of parental variables. Further, two additional indirect pathways, exclusive of fearlessness, were identified, which started with low parental warmth and positive parenting, leading to CP via CU traits. These findings support the InterFear model, demonstrating multiple pathways to CP with the involvement of fearlessness, parenting practices, and CU traits. This model might play a pivotal role in the development of targeted prevention and intervention strategies for CP.
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43.
  •  
44.
  • Hernández-Yumar, Aránzazu, et al. (författare)
  • Impact of the Economic Crisis on Body Mass Index in Spain : An Intersectional Multilevel Analysis Using a Socioeconomic and Regional Perspective
  • 2023
  • Ingår i: Population Research and Policy Review. - : Springer. - 0167-5923 .- 1573-7829. ; 42:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The Great Recession hit Spain deteriorating the living conditions of many Spanish people, increasing the prevalence of several chronic health issues, including obesity, and affecting health inequalities. We analyse the impact of this economic crisis on body mass index (BMI) disparities in Spain, from two perspectives: the socioeconomic and the territorial, through the application of an intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy. We use data from the Spanish National Health Surveys of 2006/2007, 2011/2012 and 2016/2017 to build multilevel linear regression models and estimate BMI averages and components of variance. We find a greater increase in the overall average BMI and a widening of the socioeconomic disparities during the hardest years of the crisis. However, these differences decreased when the economic situation in the country began to improve. Both socioeconomic and geographical information contribute to mapping the distribution of BMI in the population. However, according to the ICC values, considering the regional perspective provides a better understanding of the distribution of the BMI, during the period of economic crisis, in the Spanish population. Therefore, regional policies can play an important role in counteracting obesity in times of crisis.
  •  
45.
  • Hernández Yumar, Aranzazu, et al. (författare)
  • Socioeconomic differences in body mass index in Spain : An intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy
  • 2018
  • Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 13:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Many studies have demonstrated the existence of simple, unidimensional socioeconomic gradients in body mass index (BMI). However, in the present paper we move beyond such traditional analyses by simultaneously considering multiple demographic and socioeconomic dimensions. Using the Spanish National Health Survey 2011–2012, we apply intersectionality theory and multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) to analyze 14,190 adults nested within 108 intersectional strata defined by combining categories of gender, age, income, educational achievement and living situation. We develop two multilevel models to obtain information on stratum-specific BMI averages and the degree of clustering of BMI within strata expressed by the intra-class correlation coefficient (ICC). The first model is a simple variance components analysis that provides a detailed mapping of the BMI disparities in the population and measures the accuracy of stratum membership to predict individual BMI. The second model includes the variables used to define the intersectional strata as a way to identify stratum-specific interactions. The first model suggests moderate but meaningful clustering of individual BMI within the intersectional strata (ICC = 12.4%). Compared with the population average (BMI = 26.07 Kg/m2), the stratum of cohabiting 18-35-year-old females with medium income and high education presents the lowest BMI (-3.7 Kg/m2), while cohabiting 36-64-year-old females with low income and low education show the highest BMI (+2.6 Kg/m2). In the second model, the ICC falls to 1.9%, suggesting the existence of only very small stratum specific interaction effects. We confirm the existence of a socioeconomic gradient in BMI. Compared with traditional analyses, the intersectional MAIHDA approach provides a better mapping of socioeconomic and demographic inequalities in BMI. Because of the moderate clustering, public health policies aiming to reduce BMI in Spain should not solely focus on the intersectional strata with the highest BMI, but should also consider whole population polices. 
  •  
46.
  • Householder, John Ethan, et al. (författare)
  • One sixth of Amazonian tree diversity is dependent on river floodplains
  • 2024
  • Ingår i: NATURE ECOLOGY & EVOLUTION. - 2397-334X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.
  •  
47.
  • Isern, Joan, et al. (författare)
  • Self-Renewing Human Bone Marrow Mesenspheres Promote Hematopoietic Stem Cell Expansion
  • 2013
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 3:5, s. 1714-1724
  • Tidskriftsartikel (refereegranskat)abstract
    • Strategies for expanding hematopoietic stem cells (HSCs) include coculture with cells that recapitulate their natural microenvironment, such as bone marrow stromal stem/progenitor cells (BMSCs). Plastic-adherent BMSCs may be insufficient to preserve primitive HSCs. Here, we describe a method of isolating and culturing human BMSCs as nonadherent mesenchymal spheres. Human mesenspheres were derived from CD45(-) CD31(-) CD71(-) CD146(+) CD105(+) nestin(+) cells but could also be simply grown from fetal and adult BM CD45(-)-enriched cells. Human mesenspheres robustly differentiated into mesenchymal lineages. In culture conditions where they displayed a relatively undifferentiated phenotype, with decreased adherence to plastic and increased self-renewal, they promoted enhanced expansion of cord blood CD34(+) cells through secreted soluble factors. Expanded HSCs were serially transplantable in immunodeficient mice and significantly increased long-term human hematopoietic engraftment. These results pave the way for culture techniques that preserve the self-renewal of human BMSCs and their ability to support functional HSCs.
  •  
48.
  • Lopez-Romero, Laura, 1984-, et al. (författare)
  • Psychometric Properties of the Spanish Version of the Child Problematic Traits Inventory in 3-to 12-Year-Old Spanish Children
  • 2019
  • Ingår i: European Journal of Psychological Assessment. - : Hogrefe & Huber Publishers. - 1015-5759 .- 2151-2426. ; 35:6, s. 842-854
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to test the reliability and validity of the Spanish teacher-rated Child Problematic Traits Inventory (CPTI) in two community samples of 3- to 12-year-old children. Confirmatory Factor Analysis (CFA) supported the three-factor structure of the CPTI (Grandiose-Deceitful: GD; Callous-Unemotional: CU; Impulsive-Need for Stimulation: INS), being invariant across gender and age groups. The CPTI total and factor scores showed excellent internal consistencies (> .90) in the total group, and across gender and age groups. In support of their criterion validity, the CPTI scores were positively related to psychopathy scores as measured by an alternative teacher-rated measure. In support of their convergent validity, the CPTI scores showed the expected relations to variables that have been linked to psychopathic personality, including fearlessness, conduct problems, aggression, and low prosocial behavior. Overall, these findings suggest that the Spanish teacher-rated version of the CPTI has good psychometric properties and seems to be a promising tool for studying psychopathic traits in children.
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49.
  • Lozano-Hernández, Cristina M., et al. (författare)
  • Social support, social context and nonadherence to treatment in young senior patients with multimorbidity and polypharmacy followed-up in primary care. MULTIPAP Study
  • 2020
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:6
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo estimate the prevalence of nonadherence to treatment and its relationship with social support and social context in patients with multimorbidity and polypharmacy followed-up in primary care.MethodsThis was an observational, descriptive, cross-sectional, multicenter study with an analytical approach. A total of 593 patients between 65–74 years of age with multimorbidity (≥3 diseases) and polypharmacy (≥5 drugs) during the last three months and agreed to participate in the MULTIPAP Study. The main variable was adherence (Morisky-Green). The predictors were social support (structural support and functional support (DUFSS)); sociodemographic variables; indicators of urban objective vulnerability; health-related quality of life (EQ-5D-5L-VAS & QALY); and clinical variables. Descriptive, bivariate and multivariate analyses with logistic regression models and robust estimators were performed.ResultsFour out of ten patients were nonadherent, 47% had not completed primary education, 28.7% had an income ≤1050 €/month, 35% reported four or more IUVs, and the average perceived health-related quality of life (HRQOL) EQ-5D-5L-VAS was 65.5. The items that measure functional support, with significantly different means between nonadherent and adherent patients were receiving love and affection (-0.23; 95%CI: -0.40;-0.06), help when ill (-0.25; 95%CI: -0.42;-0.08), useful advice (-0.20; 95%CI: -0.37;-0.02), social invitations (-0.22; 95%CI:-0.44;-0.01), and recognition (-0.29; 95%CI:-0.50;-0.08). Factors associated with nonadherence were belonging to the medium vs. low tertile of functional support (0.62; 95%CI: 0.42;0.94), reporting less than four IUVs (0.69; 95%CI: 0.46;1.02) and higher HRQOL perception (0.98; 95%CI: 0.98;0.99).ConclusionsAmong patients 65–74 years of age with multimorbidity and polypharmacy, lower functional support was related to nonadherence to treatment. The nonadherence decreased in those patients with higher functional support, lower urban vulnerability and higher perceived health status according to the visual analog scale of health-related quality of life.
  •  
50.
  • Lozano, Rafael, et al. (författare)
  • Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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