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1.
J Clin Pharmacol ; 2020 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-32656870

RESUMO

Half-life is a standard result reported with analysis of pharmacokinetic data. Different definitions such as noncompartmental half-life, terminal half-life, effective half-life, and context-sensitive half-life can yield substantially different estimates of the quantity "half-life." Time to attainment of steady-state conditions is generally derived from (terminal) half-life and therefore sensitive toward the definition of half-life. Thus, estimates of the time to attain steady state must be provided with a precise definition of steady state and the method used for estimation, particularly for drugs with long (terminal) half-life. For clinical purposes, terminal half-life can have limited relevance if drug concentrations in the terminal elimination phase are low. A general rule for which half-life to use is infeasible. While limited accumulation can be negligible if a plateau in pharmacokinetics/pharmacodynamics is reached or with a wide therapeutic window (ie, exposure range), small additional drug accumulation can be highly relevant for drugs with a narrow therapeutic window. Beyond the average, estimation of individual time to attainment of steady state can add highly relevant information about the variability between subjects. Simulations from population models and the use of different definitions of steady state provide an assessment of robustness of the results. The relevance of accurate estimation of time to attainment of steady state is illustrated with cenerimod, an sphingosine-1-phosphate 1 receptor modulator with long half-life currently in clinical development for which estimates of time to steady state ranged from 35 to 110 days with different calculations.

2.
Sci Rep ; 10(1): 9543, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32533033

RESUMO

Wood porosity is of great interest for basic research and applications. One aspect is the cell wall porosity at total dry state. When water is absorbed by wood, the uptake of water within the cell wall leads to a dimension change of the material. A hypothesis for possible structures that hold the water is induced cell wall porosity. Nitrogen and krypton physisorption as well as high pressure hydrogen sorption and thermoporosimetry were applied to softwood and hardwood (pine and beech) in dry and wet state for determining surface area and porosity. Physisorption is not able to detect pores or surface area within the cell wall. Krypton physisorption shows surface area up 5 times lower than nitrogen with higher accuracy. With high pressure sorption no inaccessible pore volumes were seen at higher pressures. Thermoporosimetry was not able to detect mesopores within the hygroscopic water sorption region. Physisorption has to be handled carefully regarding the differences between adsorptives. The absence of water-induced mesopores within the hygroscopic region raise doubts on existing water sorption theories that assume these pore dimensions. When using the term "cell wall porosity", it is important to distinguish between pores on the cell wall surface and pores that exist because of biological structure, as there are no water-induced mesopores present. The finding offers the possibility to renew wood-water-sorption theories because based on the presented results transport of water in the cell wall must be realized by structures lower than two 2 nm. Nanoporous structures in wood at wet state should be investigated more intensively in future.

3.
Rheumatol Int ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32377959

RESUMO

Osteoporosis is a frequent comorbidity in rheumatoid arthritis (RA). Due to the improved treatment options for RA, we expect a long-term decrease in osteoporosis as an accompanying disease. Data from the German National Database (NDB) were used to investigate whether the frequency of osteoporosis has changed in the last 10 years. From 2007 to 2017, approximately 4000 patients were documented annually with data on therapy and comorbidity. The cross-sectional data were summarised descriptively. Age, sex, disease duration, disease activity and glucocorticoids were considered as influencing factors. The Cochrane-Armitage test for trend was used to test whether the frequency of osteoporosis at the first visit changed from 2007 to 2017. Osteoporosis frequency in RA patients (mean age 63 years, 75% female) decreased from 20% in 2007 to 6% in 2017 (p < 0.001). The decrease affected women (22% to 17%) and men (14% to 8%) in all age groups and both short-term (≤ 2-year disease duration: 9% to 3%) and long-term RA patients (> 10-year disease duration: 28% to 20%). Patients with high disease activity and patients who took glucocorticoids (GC) were more often affected by osteoporosis than patients in remission or without GC. Drug prophylaxis in patients without osteoporosis increased (20% to 41% without GC, 48% to 55% with GC). Men with GC received less prophylactic treatment than women (48% vs. 57% in 2017). In this cohort, osteoporosis in patients with RA is less frequently observed compared to former years. RA-specific risk factors for osteoporosis such as disease activity and GC therapy have declined but long-term GC use is still present. Assessment of osteoporosis in RA patients should be investigated more consistently by bone density measurement. Male RA patients still need to be given greater consideration regarding osteoporosis drug prophylaxis, especially when GC therapy is needed.

4.
Int J Syst Evol Microbiol ; 70(5): 3577-3581, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32320380

RESUMO

Rejection (nomen rejiciendum) of the name Borreliella and all new combinations therein is being requested on grounds of risk to human health and patient safety (Principle 1, subprinciple 2 and Rule 56a) and violation to aim for stability of names, to avoid useless creation of names (Principle 1, subprinciple 1 and 3) and that names should not be changed without sufficient reason (Principle 9 of the International Code of Nomenclature of Prokaryotes).


Assuntos
Filogenia , Spirochaetales/classificação , Terminologia como Assunto
5.
Ger Med Sci ; 18: Doc03, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32341686

RESUMO

Lyme borreliosis is the most common tick-borne infectious disease in Europe. A neurological manifestation occurs in 3-15% of infections and can manifest as polyradiculitis, meningitis and (rarely) encephalomyelitis. This S3 guideline is directed at physicians in private practices and clinics who treat Lyme neuroborreliosis in children and adults. Twenty AWMF member societies, the Robert Koch Institute, the German Borreliosis Society and three patient organisations participated in its development. A systematic review and assessment of the literature was conducted by the German Cochrane Centre, Freiburg (Cochrane Germany). The main objectives of this guideline are to define the disease and to give recommendations for the confirmation of a clinically suspected diagnosis by laboratory testing, antibiotic therapy, differential diagnostic testing and prevention.

6.
Sci Rep ; 10(1): 4410, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157151

RESUMO

Emerging drug resistance and high-attrition rates in early and late stage drug development necessitate accelerated development of antimalarial compounds. However, systematic and meaningful translation of drug efficacy and host-parasite dynamics between preclinical testing stages is missing. We developed an ensemble of mathematical within-host parasite growth and antimalarial action models, fitted to extensive data from four antimalarials with different modes of action, to assess host-parasite interactions in two preclinical drug testing systems of murine parasite P. berghei in mice, and human parasite P. falciparum in immune-deficient mice. We find properties of the host-parasite system, namely resource availability, parasite maturation and virulence, drive P. berghei dynamics and drug efficacy, whereas experimental constraints primarily influence P. falciparum infection and drug efficacy. Furthermore, uninvestigated parasite behavior such as dormancy influences parasite recrudescence following non-curative treatment and requires further investigation. Taken together, host-parasite interactions should be considered for meaningful translation of pharmacodynamic properties between murine systems and for predicting human efficacious treatment.

7.
J Clin Pharmacol ; 60(3): 369-377, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31552685

RESUMO

The current trend for clinical pharmacology is toward more complex studies (eg, umbrella protocols covering single and multiple ascending doses, food effect, metabolism pathways), requiring many decisions to be made during their conduct. This article discusses guidance of such early clinical studies by modeling and simulation. The ability to make use of all available information each time new data become available during the study requires the modeling scientist to be unblinded. This must of course not jeopardize the blinding of the clinical team, and this article discusses how unblinding can be prevented. Although modeling and simulation are established for guidance of the drug development process overall, they are not frequently used for guidance on a small scale, that is, during studies with the largest uncertainty, the first-in-human studies. Application of a quantitative model backbone makes early clinical drug development a more efficient process and provides additional safety for healthy subjects and patients. Real clinical impact is illustrated by 3 case studies that show different contributions from unblinded modeling: dose escalation based on safety data, modeling and predicting with explicit incorporation of in vitro data, and dose escalation supported by unblinded analysis of adverse event data, which resulted in new insights of the clinical team without being unblinded and made it possible to proceed with dose escalation and to extend the study with an up-titration group.

8.
Br J Clin Pharmacol ; 86(4): 791-800, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31756016

RESUMO

AIMS: Assessment of time to attain steady state as well as drug accumulation following long-term treatment with the selective sphingosine-1-phosphate 1 receptor modulator cenerimod and prediction of the incidence of low total lymphocyte (LY) counts. Differences in pharmacokinetics and pharmacodynamics based on demographic characteristics and between healthy subjects and systemic lupus erythematosus (SLE) patients were to be identified. METHODS: Data from 4 Phase I studies and 1 Phase II study were pooled to develop a population pharmacokinetic/pharmacodynamic model describing cenerimod concentration and its effect on LY count. Simulations addressed the objectives. RESULTS: Simulations of 365 days of treatment indicated a time to steady state of 49 days and changes in exposure of 15% beyond 35 days. For a dose of 2 mg, the predicted incidences of LY counts below 0.5 and 0.2 × 109 cells/L were 18.2 and 0.6% for healthy subjects and 25.9 and 1.0% for SLE patients, respectively. Incidence increased with higher dose and lower baseline LY counts. For body weights of 50 and 100 kg compared to 75 kg, exposure was predicted to change by +37% and -20%, respectively. CONCLUSION: Long-term cenerimod administration is not expected to result in exposure and LY count reduction substantially different from results of completed studies. Low LY counts are predicted to occur more frequently in SLE patients compared to healthy subjects. Dose individualization based on the model is not considered necessary. Model-based simulations enable benefit-risk evaluations, supporting planning of late-phase clinical studies and scientific exchange with health authorities.

9.
Pharm Res ; 37(1): 2, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823033

RESUMO

PURPOSE: Bosentan, clazosentan, and tezosentan are three small-molecule endothelin receptor antagonists (ERAs), displacing endothelin-1 (ET-1) from its binding site. A target-mediated drug disposition (TMDD) pharmacokinetic (PK) model described the non-linearity in the PK of bosentan caused by its high receptor binding affinity with time-dependent varying receptor expression or reappearance. The aim of this analysis was to investigate the presence of TMDD for clazosentan and tezosentan and to corroborate the hypothesis of a diurnal receptor synthesis. METHODS: PK data from healthy subjects after intravenous (i.v.) administration of single ascending doses of bosentan, clazosentan, and tezosentan were analyzed. Frequent blood samples for PK measurements were collected. Population analyses, simulations, and evaluations were performed using a non-linear mixed-effects modeling approach. RESULTS: Two-compartment TMDD models were successfully developed describing the PK of all three ERAs with different receptor-complex internalization properties. The observed multiple peaks in the concentration-time profiles were captured with cosine functions on the receptor synthesis rate mimicking a diurnal receptor expression or reappearance. The results strongly suggest that TMDD is a class effect of ERAs. CONCLUSION: The developed TMDD PK models are a next step towards understanding the complex PK of ERAs and further support the hypothesis that TMDD is a class effect of ERAs.


Assuntos
Bosentana/farmacocinética , Dioxanos/farmacocinética , Antagonistas dos Receptores de Endotelina/farmacocinética , Modelos Biológicos , Piridinas/farmacocinética , Pirimidinas/farmacocinética , Receptores de Endotelina/metabolismo , Sulfonamidas/farmacocinética , Tetrazóis/farmacocinética , Bosentana/administração & dosagem , Dioxanos/administração & dosagem , Relação Dose-Resposta a Droga , Antagonistas dos Receptores de Endotelina/administração & dosagem , Humanos , Infusões Intravenosas , Masculino , Dinâmica não Linear , Piridinas/administração & dosagem , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagem , Espectrometria de Massas em Tandem , Tetrazóis/administração & dosagem
10.
Sci Rep ; 9(1): 10309, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311949

RESUMO

An investigation of simultaneous dynamic mass and length change measurement for wood is presented. In contrast to the equilibrium in moisture content and swelling and shrinking, where extensive data exists for different wood species, less information is available for the dynamics of moisture changes in direct comparison to the related dimensional changes during the sorption process. This is due to a lack of methods. A gravimetric sorption system, equipped with a high resolution camera and an automated image evaluation, is used to examine simultaneous effects of water vapour sorption dynamics and dimensional change. This method proves a strong correlation between mass and dimensional change, which is in contrast to other investigations. Equilibrium moisture content as well as swelling and shrinking data is in good agreement with literature and manual measurements. The method enables the possibility to determine swelling and shrinking values in-situ without disturbing the targeted climatic conditions. The system is applicable for the investigation of natural wood, modified wood, wood composites or other lignocellulosic materials.

11.
J Clin Med Res ; 11(6): 391-400, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31143305

RESUMO

Background: Spondylarthritis (SpA) significantly affects sacroiliac, intervertebral and peripheral joints. Patients with SpA suffer from increased cardiovascular risk (CVR). The endothelial progenitor cell (EPC) system critically perpetuates vascular repair. The aim of the study was to evaluate circulating EPCs in axial (ax)SpA with special attention on parameters of disease activity and CVR. Methods: Disease activity and functional impairment were quantified in 50 axSpA patients by using standardized parameters (Bath ankylosing spondylitis disease activity index (BASDAI), C-reactive protein (CRP), finger-floor distance (FFD) and Ott' sign). Circulating EPCs and EPC regeneration were analyzed (fluorescence-activated cell sorting (FACS) and colony-forming unit (CFU) assay). Serum vasomodulatory mediators were quantified by enzyme-linked immunosorbent assay (ELISA). Results: EPC colony numbers were lower in axSpA as compared to controls. Females displayed more colonies than males. In addition, fewer colonies were observed in smokers, in patients with a BASDAI of below 4 and in hypertension. Circulating CD133+/KDR+ cells did not differ between the groups. Follow-up analysis (33 months later) did not show any differences in gender, colony formation, CD133+/KDR+ cells or serum levels of vasomodulatory mediators if related to the categories of BASDAI, Ott' sign or FFD. Conclusions: EPC colony formation is significantly affected in axSpA with particularly low levels in males. EPC-related parameters do not allow predicting disease activity-related or functional parameters nor are they useful for CVR assessment in SpA.

13.
Z Rheumatol ; 78(3): 218-220, 2019 04.
Artigo em Alemão | MEDLINE | ID: mdl-30941588

Assuntos
Comorbidade
14.
Micron ; 117: 22-28, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30447491

RESUMO

X-ray micro-computed tomography (XµCT) allows a non-destructive and three-dimensional (3D) study of otherwise complex and opaque wood tissues. In wood research, XµCT datasets are highly useful for the qualitative and quantitative examination of wood structures. In this study, XµCT was introduced and tested for examining X-ray dense silica particles in the Australian turpentine wood (Syncarpia glomulifera). It was possible to three-dimensionally visualize and numerically quantify silica particles. Numerical analysis was performed to scrutinize the size and content of silica particles. In comparative studies of silica size through scanning electron microscopy and silica content through thermo-gravimetric analysis after acid digestion of ash, our findings pointed out that XµCT is indeed a powerful tool for examining silica particles in wood; because XµCT enables a simultaneous visualization and quantification of the silica particles in 3D without being destructive. Despite these benefits, comparative examination through scanning electron microscopy and energy-dispersive X-ray spectroscopy is necessary to verify silica particles in tomographic images. XµCT technology might further aid in probing the biological and ecological function of silica in silica-bearing wood species.

15.
Cogn Sci ; 42(8): 2592-2620, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30390325

RESUMO

How do people pursue rewards in risky environments, where some outcomes should be avoided at all costs? We investigate how participant search for spatially correlated rewards in scenarios where one must avoid sampling rewards below a given threshold. This requires not only the balancing of exploration and exploitation, but also reasoning about how to avoid potentially risky areas of the search space. Within risky versions of the spatially correlated multi-armed bandit task, we show that participants' behavior is aligned well with a Gaussian process function learning algorithm, which chooses points based on a safe optimization routine. Moreover, using leave-one-block-out cross-validation, we find that participants adapt their sampling behavior to the riskiness of the task, although the underlying function learning mechanism remains relatively unchanged. These results show that participants can adapt their search behavior to the adversity of the environment and enrich our understanding of adaptive behavior in the face of risk and uncertainty.


Assuntos
Tomada de Decisões/fisiologia , Generalização Psicológica/fisiologia , Modelos Psicológicos , Assunção de Riscos , Adulto , Algoritmos , Feminino , Humanos , Aprendizagem/fisiologia , Masculino , Incerteza , Adulto Jovem
16.
Nat Commun ; 9(1): 2938, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30087330

RESUMO

Scenarios that limit global warming to below 2 °C by 2100 assume significant land-use change to support large-scale carbon dioxide (CO2) removal from the atmosphere by afforestation/reforestation, avoided deforestation, and Biomass Energy with Carbon Capture and Storage (BECCS). The more ambitious mitigation scenarios require even greater land area for mitigation and/or earlier adoption of CO2 removal strategies. Here we show that additional land-use change to meet a 1.5 °C climate change target could result in net losses of carbon from the land. The effectiveness of BECCS strongly depends on several assumptions related to the choice of biomass, the fate of initial above ground biomass, and the fossil-fuel emissions offset in the energy system. Depending on these factors, carbon removed from the atmosphere through BECCS could easily be offset by losses due to land-use change. If BECCS involves replacing high-carbon content ecosystems with crops, then forest-based mitigation could be more efficient for atmospheric CO2 removal than BECCS.

17.
MAbs ; 10(6): 934-943, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30010481

RESUMO

This multinational, randomized, double-blind trial, (ClinicalTrials.gov identifier NCT02149121) was designed to demonstrate equivalence in pharmacokinetics and efficacy between CT-P10 and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA). Adults with active RA were treated with CT-P10, United States-sourced RTX (US-RTX; Rituxan®), or European Union-sourced RTX (EU-RTX; MabThera®) at weeks 0 and 2. The co-primary pharmacokinetic endpoints were area under the serum concentration-time curve (AUC) from time zero to last measurable concentration (AUC0-last), AUC from time zero to infinity (AUC0-∞), and maximum concentration (Cmax) after two infusions. The primary efficacy endpoint was change from baseline to week 24 in Disease Activity Score using 28 joints-C-reactive protein (DAS28-CRP). Pharmacodynamics, immunogenicity, and safety were also assessed. 372 patients were randomly assigned to CT-P10 (n = 161) or RTX (n = 211 [US-RTX, n = 151; EU-RTX, n = 60]). For the co-primary pharmacokinetic endpoints, 90% confidence intervals (CI) for ratios of geometric means (CT-P10/US-RTX, CT-P10/EU-RTX or EU-RTX/US-RTX) all fell within the equivalence margin of 80-125%. Adjusted least squares (LS) mean (standard error) change from baseline in DAS28-CRP at week 24 was -2.13 (0.175) for CT-P10 and -2.09 (0.176) for RTX. The 95% CI (-0.29, 0.21) of the estimated treatment difference between CT-P10 and RTX (-0.04) was entirely within the efficacy equivalence margin of ±0.5. Pharmacodynamics, immunogenicity, and safety profiles were similar for CT-P10 and RTX. The pharmacokinetics of CT-P10, US-RTX, and EU-RTX were equivalent. CT-P10 and RTX were also equivalent in terms of efficacy and displayed similar pharmacodynamic, immunogenicity, and safety profiles up to week 24.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/uso terapêutico , Rituximab/uso terapêutico , Adulto , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/farmacocinética , Antirreumáticos/efeitos adversos , Antirreumáticos/farmacocinética , Antirreumáticos/uso terapêutico , Área Sob a Curva , Artrite Reumatoide/metabolismo , Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/farmacocinética , Método Duplo-Cego , Feminino , Humanos , Infecções/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Rituximab/efeitos adversos , Rituximab/farmacocinética , Equivalência Terapêutica , Resultado do Tratamento
18.
Eur J Pharmacol ; 833: 379-391, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29935174

RESUMO

An estimated 240 million people worldwide are chronically infected with the hepatitis B virus (HBV). Despite readily available vaccination, HBV infections remain highly prevalent. As established HBV infections constitute a strong risk factor for developing hepatocellular carcinoma their treatment is a major task for the health system. Unfortunately, HBV is not curable with today's medicine. Approximately 15 million HBV patients have developed a hepatitis delta (HDV) infection on top of their HBV infection. The patients superinfected with this satellite virus suffer from a more severe disease development. The knowledge of the viruses, their classifications, clinical implications, treatment options and efforts to increase the drug variety are compiled in this review. The current standard therapies include nucleosidic reverse transcriptase inhibitors and interferon. As the known treatments fail to cure HBV and HDV, targeted treatment is highly warranted. The focus of this review is set on the drugs currently under clinical investigation. Furthermore, strategies for the development of targeted treatment, and compounds with novel mode of action are described.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite D/tratamento farmacológico , Superinfecção/tratamento farmacológico , Antivirais/farmacologia , Antivirais/normas , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Hepatocelular/virologia , Ensaios Clínicos como Assunto , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/transmissão , Hepatite B Crônica/virologia , Hepatite D/epidemiologia , Hepatite D/transmissão , Hepatite D/virologia , Vírus Delta da Hepatite/efeitos dos fármacos , Hepatócitos/virologia , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/virologia , Guias de Prática Clínica como Assunto , Prevalência , Superinfecção/epidemiologia , Superinfecção/virologia , Resultado do Tratamento , Replicação Viral/efeitos dos fármacos
19.
Clin Rheumatol ; 37(7): 1835-1844, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29656375

RESUMO

To examine disease activity parameters in patients with systemic lupus erythematosus (SLE) experiencing flare, infection, both, or neither condition, focusing on erythrocyte sedimentation rate (ESR). This study is a retrospective analysis of 371 consecutive inpatient SLE cases from 2006 to 2015. Cases were classified as flare (n = 147), infection (n = 48), both (n = 23), or neither (n = 135). ESR levels were correlated to C-reactive protein (CRP), ferritin, anti-dsDNA antibodies, complement C3 reduction, serositis, and erythrocyturia with proteinuria (Pearson's correlation). ESR levels were related to an age- and gender-adapted cut-off value (ESRp). We analyzed mean values of age, ESR, ESRp, CRP, ferritin and distribution of anti-dsDNA antibodies, C3 reduction, serositis, and erythrocyturia with proteinuria. Sensitivity and specificity were calculated via receiver operating characteristic or two-by-two table. Association of parameters with disease activity and infection was tested via two-sided chi square test. ESR correlated moderately with CRP in cases with flare and/or infection (r = 0.505-0.586). While ESR and CRP were normal in remission, mean values overlapped in cases with flare, infection, or both. ESRp was higher in flare than in infection (p = 0.048). ESR lost association to activity in infected cases, CRP to infection in flaring cases. ESRp, serositis, and anti-dsDNA antibodies were related to disease activity regardless of infections. Anti-dsDNA antibodies were most sensitive for detecting flares (74%), while serositis, proteinuria with erythrocyturia, anti-dsDNA antibodies, C3 reduction, and ESRp values ≥ 2 were most specific. ESR levels were raised by flares, infections, and age; adapting them to age and gender increased their diagnostic value. Obtaining several parameters remains necessary to differentiate flare from infection.


Assuntos
Sedimentação Sanguínea , Infecções/sangue , Lúpus Eritematoso Sistêmico/sangue , Exacerbação dos Sintomas , Proteína C-Reativa/análise , Humanos , Infecções/complicações , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Curva ROC , Estudos Retrospectivos
20.
Glob Chang Biol ; 24(7): 3025-3038, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29569788

RESUMO

Most climate mitigation scenarios involve negative emissions, especially those that aim to limit global temperature increase to 2°C or less. However, the carbon uptake potential in land-based climate change mitigation efforts is highly uncertain. Here, we address this uncertainty by using two land-based mitigation scenarios from two land-use models (IMAGE and MAgPIE) as input to four dynamic global vegetation models (DGVMs; LPJ-GUESS, ORCHIDEE, JULES, LPJmL). Each of the four combinations of land-use models and mitigation scenarios aimed for a cumulative carbon uptake of ~130 GtC by the end of the century, achieved either via the cultivation of bioenergy crops combined with carbon capture and storage (BECCS) or avoided deforestation and afforestation (ADAFF). Results suggest large uncertainty in simulated future land demand and carbon uptake rates, depending on the assumptions related to land use and land management in the models. Total cumulative carbon uptake in the DGVMs is highly variable across mitigation scenarios, ranging between 19 and 130 GtC by year 2099. Only one out of the 16 combinations of mitigation scenarios and DGVMs achieves an equivalent or higher carbon uptake than achieved in the land-use models. The large differences in carbon uptake between the DGVMs and their discrepancy against the carbon uptake in IMAGE and MAgPIE are mainly due to different model assumptions regarding bioenergy crop yields and due to the simulation of soil carbon response to land-use change. Differences between land-use models and DGVMs regarding forest biomass and the rate of forest regrowth also have an impact, albeit smaller, on the results. Given the low confidence in simulated carbon uptake for a given land-based mitigation scenario, and that negative emissions simulated by the DGVMs are typically lower than assumed in scenarios consistent with the 2°C target, relying on negative emissions to mitigate climate change is a highly uncertain strategy.


Assuntos
Carbono/metabolismo , Mudança Climática , Biomassa , Ciclo do Carbono , Dióxido de Carbono/análise , Sequestro de Carbono , Conservação dos Recursos Naturais , Produtos Agrícolas , Florestas , Solo , Incerteza
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