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Solar particle events (SPEs) are short-lived bursts of high-energy particles from the solar atmosphere and are widely recognized as posing significant economic risks to modern society. Most SPEs are relatively weak and have minor impacts on the Earth's environment, but historic records contain much stronger SPEs which have the potential to alter atmospheric chemistry, impacting climate and biological life. The impacts of such strong SPEs would be far more severe when the Earth's protective geomagnetic field is weak, such as during past geomagnetic excursions or reversals. Here, we model the impacts of an extreme SPE under different geomagnetic field strengths, focusing on changes in atmospheric chemistry and surface radiation using the atmosphere-ocean-chemistry-climate model SOCOL3-MPIOM and the radiation transfer model LibRadtran. Under current geomagnetic conditions, an extreme SPE would increase NOx concentrations in the polar stratosphere and mesosphere, causing reductions in extratropical stratospheric ozone lasting for about a year. In contrast, with no geomagnetic field, there would be a substantial increase in NOx throughout the entire atmosphere, resulting in severe stratospheric ozone depletion for several years. The resulting ground-level ultraviolet (UV) radiation would remain elevated for up to 6 y, leading to increases in UV index up to 20 to 25% and solar-induced DNA damage rates by 40 to 50%. The potential evolutionary impacts of past extreme SPEs remain an important question, while the risks they pose to human health in modern conditions continue to be underestimated.
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Tropospheric ozone is an air pollutant that poses a public health problem in Europe. Climate change could increase the formation of ozone. Applying past and predicted annual total (all-cause) mortality data and modeled daily ozone concentrations, we performed a nationwide health impact assessment estimating annual ozone-related (attributable) deaths in Austria. Different approaches were compared. Estimates were based on maximal 1-h averages of ozone. Until the decade from 2045 till 2055, more people will die in Austria because of the demographic trends. Therefore, more deaths will also be attributable to ozone. Higher greenhouse gas emission scenarios (e.g. Representative Concentration Pathway RCP8.5 compared to RCP2.6) will lead to more ozone-related deaths, mostly due to the national emission of ozone precursors (a difference of 250-340 cases per year, depending on the model), but to a lesser extent because of global climate change. Increases in attributable deaths will be affected mostly by national, not global mitigation measures. National emission reduction will certainly have a strong and beneficial effect on local atmospheric chemistry, air quality, and public health.
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Future air quality will be driven by changes in air pollutant emissions, but also changes in climate. Here, we review the recent literature on future air quality scenarios and projected changes in effects on human health, crops and ecosystems. While there is overlap in the scenarios and models used for future projections of air quality and climate effects on human health and crops, similar efforts have not been widely conducted for ecosystems. Few studies have conducted joint assessments across more than one sector. Improvements in future air quality effects on human health are seen in emission reduction scenarios that are more ambitious than current legislation. Larger impacts result from changing particulate matter (PM) abundances than ozone burdens. Future global health burdens are dominated by changes in the Asian region. Expected future reductions in ozone outside of Asia will allow for increased crop production. Reductions in PM, although associated with much higher uncertainty, could offset some of this benefit. The responses of ecosystems to air pollution and climate change are long-term, complex, and interactive, and vary widely across biomes and over space and time. Air quality and climate policy should be linked or at least considered holistically, and managed as a multi-media problem. This article is part of a discussion meeting issue 'Air quality, past present and future'.
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Poluição do Ar/efeitos adversos , Produtos Agrícolas , Ecossistema , Poluição do Ar/prevenção & controle , Mudança Climática , Meio Ambiente , Saúde Ambiental , Saúde Global , Humanos , Modelos BiológicosRESUMO
The 2016 revised World Health Organization (WHO) classification of lymphoid neoplasms included the category of high-grade B cell lymphomas (HGBLs) with combined MYC and BCL2 and/or BCL6 rearrangements (double-hit, DH). However, the clinical features of B cell precursor leukemia (BCP-ALL) that harbor DH genetics remain widely unknown. We performed a retrospective analysis of the German Multicenter Study Group for Adult ALL registry and a literature search for de novo DH-BCP-ALLs. We identified 6 patients in the GMALL registry and 11 patients published in the literature between 1983 and June 2018. Patients of all ages (range, 15-86 years) are affected. There is a high incidence of meningeal disease and other extramedullary disease manifestations. Current treatment approaches are mainly ALL-based and are sufficient to induce first complete remissions, but progression-free survival is only 4.0 months (95% CI, 1.5-6.5 months) and all patients succumb to their disease, once relapsed, with a median survival of 5.0 months (95% CI, 3.1-6.9 months), despite intensive salvage and targeted therapy approaches. Of all patients, only two that attained an initial complete remission were alive at data cutoff. In all cases, the BCL2 gene was rearranged to be in proximity to the IGH locus, whereas MYC had various translocation partners juxtaposed. There was no significant survival difference between IG and non-IG translocation partners (HR, 1.03; 95% CI, 0.33-3.2; p = 0.89). In conclusion, de novo DH-BCP-ALL is an aggressive B cell malignancy with deleterious outcome. Physicians have to be aware of this rare disease subset due to the atypical clinical behavior and especially because latest classification systems do not cover this sub-entity.
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Genes bcl-2 , Genes myc , Leucemia-Linfoma Linfoblástico de Células Precursoras/classificação , Proteínas Proto-Oncogênicas c-bcl-6/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Rearranjo Gênico do Linfócito B , Humanos , Infiltração Leucêmica , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Intervalo Livre de Progressão , Recidiva , Terapia de Salvação , Translocação Genética , Adulto JovemRESUMO
While capabilities in urban climate modeling have substantially increased in recent decades, the interdependency of changes in environmental surface properties and human (dis)comfort have only recently received attention. The open-source solar long-wave environmental irradiance geometry (SOLWEIG) model is one of the state-of-the-art models frequently used for urban (micro-)climatic studies. Here, we present updated calculation schemes for SOLWEIG allowing the improved prediction of surface temperatures (wall and ground). We illustrate that parameterizations based on measurements of global radiation on a south-facing vertical plane obtain better results compared to those based on solar elevation. Due to the limited number of ground surface temperature parameterizations in SOLWEIG, we implement the two-layer force-restore method for calculating ground temperature for various soil conditions. To characterize changes in urban canyon air temperature (Tcan), we couple the calculation method as used in the Town Energy Balance (TEB) model. Comparison of model results and observations (obtained during field campaigns) indicates a good agreement between modeled and measured Tcan, with an explained variance of R2 = 0.99. Finally, we implement an energy balance model for vertically mounted PV modules to contrast different urban surface properties. Specifically, we consider (i) an environment comprising dark asphalt and a glass facade and (ii) an environment comprising bright concrete and a PV facade. The model results show a substantially decreased Tcan (by up to - 1.65°C) for the latter case, indicating the potential of partially reducing/mitigating urban heat island effects.
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Clima , Microclima , Cidades , Humanos , Modelos Teóricos , TemperaturaRESUMO
This largest prospective multicenter trial for adult patients with Burkitt lymphoma/leukemia aimed to prove the efficacy and feasibility of short-intensive chemotherapy combined with the anti-CD20 antibody rituximab. From 2002 to 2011, 363 patients 16 to 85 years old were recruited in 98 centers. Treatment consisted of 6 5-day chemotherapy cycles with high-dose methotrexate, high-dose cytosine arabinoside, cyclophosphamide, etoposide, ifosphamide, corticosteroids, and triple intrathecal therapy. Patients >55 years old received a reduced regimen. Rituximab was given before each cycle and twice as maintenance, for a total of 8 doses. The rate of complete remission was 88% (319/363); overall survival (OS) at 5 years, 80%; and progression-free survival, 71%; with significant difference between adolescents, adults, and elderly patients (OS rate of 90%, 84%, and 62%, respectively). Full treatment could be applied in 86% of the patients. The most important prognostic factors were International Prognostic Index (IPI) score (0-2 vs 3-5; P = .0005), age-adjusted IPI score (0-1 vs 2-3; P = .0001), and gender (male vs female; P = .004). The high cure rate in this prospective trial with a substantial number of participating hospitals demonstrates the efficacy and feasibility of chemoimmunotherapy, even in elderly patients. This trial was registered at www.clinicaltrials.gov as #NCT00199082.
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Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma de Burkitt/tratamento farmacológico , Leucemia/tratamento farmacológico , Adolescente , Corticosteroides/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD20/imunologia , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Imunoterapia/métodos , Injeções Espinhais , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Indução de Remissão , Rituximab , Adulto JovemRESUMO
Cornelia de Lange syndrome (CdLS) is a well-characterized developmental disorder. The genetic cause of CdLS is a mutation in one of five associated genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8) accounting for about 70% of cases. To improve our current molecular diagnostic and to analyze some of CdLS candidate genes, we developed and established a gene panel approach. Because recent data indicate a high frequency of mosaic NIPBL mutations that were not detected by conventional sequencing approaches of blood DNA, we started to collect buccal mucosa (BM) samples of our patients that were negative for mutations in the known CdLS genes. Here, we report the identification of three mosaic NIPBL mutations by our high-coverage gene panel sequencing approach that were undetected by classical Sanger sequencing analysis of BM DNA. All mutations were confirmed by the use of highly sensitive SNaPshot fragment analysis using DNA from BM, urine, and fibroblast samples. In blood samples, we could not detect the respective mutation. Finally, in fibroblast samples from all three patients, Sanger sequencing could identify all the mutations. Thus, our study highlights the need for highly sensitive technologies in molecular diagnostic of CdLS to improve genetic diagnosis and counseling of patients and their families.
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Síndrome de Cornélia de Lange/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Proteínas/genética , Análise de Sequência de DNA/métodos , Proteínas de Ciclo Celular , Criança , Pré-Escolar , Síndrome de Cornélia de Lange/genética , Feminino , Predisposição Genética para Doença , Humanos , Adulto JovemRESUMO
Unbiased amplification of the whole-genome amplification (WGA) of single cells is crucial to study cancer evolution and genetic heterogeneity, but is challenging due to the high complexity of the human genome. Here, we present a new workflow combining an efficient adapter-linker PCR-based WGA method with second-generation sequencing. This approach allows comparison of single cells at base pair resolution. Amplification recovered up to 74% of the human genome. Copy-number variants and loss of heterozygosity detected in single cell genomes showed concordance of up to 99% to pooled genomic DNA. Allele frequencies of mutations could be determined accurately due to an allele dropout rate of only 2%, clearly demonstrating the low bias of our PCR-based WGA approach. Sequencing with paired-end reads allowed genome-wide analysis of structural variants. By direct comparison to other WGA methods, we further endorse its suitability to analyze genetic heterogeneity.
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Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Análise de Célula Única/métodos , Aberrações Cromossômicas , Variações do Número de Cópias de DNA , Frequência do Gene , Heterogeneidade Genética , Humanos , Perda de Heterozigosidade , Reação em Cadeia da Polimerase/métodos , Reprodutibilidade dos Testes , Fluxo de TrabalhoRESUMO
Quantification of minimal residual disease (MRD) by real-time PCR directed to TCR and Ig gene rearrangements allows a refined evaluation of response in acute lymphoblastic leukemia (ALL). The German Multicenter Study Group for Adult ALL prospectively evaluated molecular response after induction/consolidation chemotherapy according to standardized methods and terminology in patients with Philadelphia chromosome-negative ALL. The cytologic complete response (CR) rate was 89% after induction phases 1 and 2. At this time point the molecular CR rate was 70% in 580 patients with cytologic CR and evaluable MRD. Patients with molecular CR after consolidation had a significantly higher probability of continuous complete remission (CCR; 74% vs 35%; P < .0001) and of overall survival (80% vs 42%; P = .0001) compared with patients with molecular failure. Patients with molecular failure without stem cell transplantation (SCT) in first CR relapsed after a median time of 7.6 months; CCR and survival at 5 years only reached 12% and 33%, respectively. Quantitative MRD assessment identified patients with molecular failure as a new high-risk group. These patients display resistance to conventional drugs and are candidates for treatment with targeted, experimental drugs and allogeneic SCT. Molecular response was shown to be highly predictive for outcome and therefore constitutes a relevant study end point. The studies are registered at www.clinicaltrials.gov as NCT00199056 and NCT00198991.
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Transplante de Células-Tronco Hematopoéticas/métodos , Quimioterapia de Indução/métodos , Neoplasia Residual/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Terapia Combinada , Humanos , Pessoa de Meia-Idade , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Prognóstico , Estudos Prospectivos , Indução de Remissão , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
We investigate the performance of two widely used chemistry-transport models (CTMs) with different chemical mechanisms in reproducing the ambient maximum daily 8-h average ozone (MDA8 O3) burden over Central Europe. We explore a base case setup with boundary conditions (BC) for meteorology from the ERA-Interim reanalysis and chemical BC from CAM-Chem as well as effects of alterations in these BC based on global model fields. Our results show that changes in meteorological BC strongly affect the correlation with observations but only marginally affect the model biases, while changes in chemical BC increase model biases while correlation patterns remain largely unchanged. Furthermore, our study highlights that CTM choice (and choice of chemical mechanism) has a similar or even larger impact on MDA8 O3 levels as the impact of altered BC. In summary, our study calls for a multi-model strategy combining different CTM and BC combinations to explore the bandwidth of MDA8 O3 distributions and thus uncertainty in hindcasts and future projections, in analogy to climate studies considering ensemble simulations under the same anthropogenic emissions but with slightly different initial conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s11869-024-01516-3.
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In this study we examine the determination accuracy of both the mean radiant temperature (Tmrt) and the Universal Thermal Climate Index (UTCI) within the scope of numerical weather prediction (NWP), and global (GCM) and regional (RCM) climate model simulations. First, Tmrt is determined and the so-called UTCI-Fiala model is then used for the calculation of UTCI. Taking into account the uncertainties of NWP model (among others the HIgh Resolution Limited Area Model HIRLAM) output (temperature, downwelling short-wave and long-wave radiation) stated in the literature, we simulate and discuss the uncertainties of Tmrt and UTCI at three stations in different climatic regions of Europe. The results show that highest negative (positive) differences to reference cases (under assumed clear-sky conditions) of up to -21°C (9°C) for Tmrt and up to -6°C (3.5°C) for UTCI occur in summer (winter) due to cloudiness. In a second step, the uncertainties of RCM simulations are analyzed: three RCMs, namely ALADIN (Aire Limitée Adaptation dynamique Développement InterNational), RegCM (REGional Climate Model) and REMO (REgional MOdel) are nested into GCMs and used for the prediction of temperature and radiation fluxes in order to estimate Tmrt and UTCI. The inter-comparison of RCM output for the three selected locations shows that biases between 0.0 and ±17.7°C (between 0.0 and ±13.3°C) for Tmrt (UTCI), and RMSE between ±0.5 and ±17.8°C (between ±0.8 and ±13.4°C) for Tmrt (UTCI) may be expected. In general the study shows that uncertainties of UTCI, due to uncertainties arising from calculations of radiation fluxes (based on NWP models) required for the prediction of Tmrt, are well below ±2°C for clear-sky cases. However, significant higher uncertainties in UTCI of up to ±6°C are found, especially when prediction of cloudiness is wrong.
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Clima , Modelos Teóricos , Europa (Continente) , Energia Solar , Incerteza , Tempo (Meteorologia)RESUMO
Burkitt lymphoma and a subset of diffuse large B-cell lymphomas are characterized by chromosomal alterations affecting the MYC oncogene on 8q24. In most cases MYC is found juxtaposed to the immunoglobulin heavy chain (IGH) gene locus. Translocations to the immunoglobulin kappa (IGK) gene locus on 2p11 are observed in around 5-10% of cases. Little data exist on the molecular mechanisms leading to this aberration. The chromosomal breakpoints on chromosome 8 have been found dispersed over a large area 3' of MYC. In order to obtain a better understanding of this chromosomal translocation we developed a long-distance inverse (LDI) PCR method for the identification of chromosomal translocations affecting the IGK locus. We investigated a number of cytogenetically mostly uncharacterized high-grade lymphoma samples and identified a MYC-IGK juxtaposition in seven patients and three t(2;8)-positive cell lines. The chromosomal breakpoints were molecularly characterized and analyzed. The linear distance of the breakpoints on chromosome 8 to MYC ranged from some 100 bp to more than 0.5 MB. The reciprocal translocated allele could be characterized in the majority of cases. This study represents the largest series of t(2;8)-positive cases analyzed so far. The LDI PCR method developed here should also be useful for the analysis of chromosomal translocations affecting the IGK locus in general.
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Cadeias kappa de Imunoglobulina/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Linfoma não Hodgkin/genética , Proteínas Proto-Oncogênicas c-myc/genética , Translocação Genética/genética , Adulto , Idoso , Pontos de Quebra do Cromossomo , Mapeamento Cromossômico , Cromossomos Humanos Par 2/genética , Cromossomos Humanos Par 8/genética , Análise Citogenética , Feminino , Loci Gênicos , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Células K562 , Linfoma de Células B/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodosRESUMO
While the MLL "recombinome" is relatively well characterized in B-cell precursor acute lymphoblastic leukemia (BCP ALL), available data for adult acute T-lymphoblastic leukemia (T-ALL) are scarce. We performed fluorescence in situ hybridization (FISH) for an MLL split signal on 223 adult T-ALL samples obtained within the framework of the German Multicenter ALL 07/2003 therapy trial. Three biphenotypic leukemias (T-ALL/AML) were also included in the analysis. Samples showing any alteration by FISH were further investigated to characterize the MLL aberration. In addition, they were investigated for common genetic lesions known in T-ALL. Twenty-two cases (9.5%) showed an abnormal MLL signal by FISH analysis. Most of these appeared to be deletions or gains but in five cases (2.1%) a chromosomal translocation involving the MLL gene was identified. The translocation partners and chromosomal breakpoints were molecularly characterized. Three T-ALLs had an MLL-AF6/t(6;11) and two biphenotypic leukemias had an MLL-ELL/t(11;19). The chromosomal breakpoints in two of the MLL-AF6-positive cases were located outside the classical MLL major breakpoint cluster known from BCP ALL. In conclusion, the spectrum of MLL translocation partners in adult T-ALL much more resembles that of AML than that of BCP ALL and thus the mechanisms by which MLL contributes to leukemogenesis in adult T-ALL appear to differ from those in BCP ALL. Proposals are made for the diagnostic assessment of MLL fusion genes in adult T-ALL.
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Proteína de Leucina Linfoide-Mieloide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Estudos de Associação Genética , Histona-Lisina N-Metiltransferase , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Translocação GenéticaRESUMO
Excess reactive nitrogen (Nr), including nitrogen oxides (NOx) and ammonia (NH3), contributes strongly to fine particulate matter (PM2.5) air pollution in Europe, posing challenges to public health. Designing cost-effective Nr control roadmaps for PM2.5 mitigation requires considering both mitigation efficiencies and implementation costs. Here we identify optimal Nr control pathways for Europe by integrating emission estimations, air quality modeling, exposure-mortality modeling, Nr control experiments and cost data. We find that phasing out Nr emissions would reduce PM2.5 by 2.3 ± 1.2 µg·m-3 in Europe, helping many locations achieve the World Health Organization (WHO) guidelines and reducing PM2.5-related premature deaths by almost 100 thousand in 2015. Low-ambition NH3 controls have similar PM2.5 mitigation efficiencies as NOx in Eastern Europe, but are less effective in Western Europe until reductions exceed 40%. The efficiency for NH3 controls increases at high-ambition reductions while NOx slightly decreases. When costs are considered, strategies for both regions uniformly shift in favor of NH3 controls, as NH3 controls up to 50% remain 5-11 times more cost-effective than NOx per unit PM2.5 reduction, emphasizing the priority of NH3 control policies for Europe.
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In the present study, we investigate the determination accuracy of the Universal Thermal Climate Index (UTCI). We study especially the UTCI uncertainties due to uncertainties in radiation fluxes, whose impacts on UTCI are evaluated via the mean radiant temperature (Tmrt). We assume "normal conditions", which means that usual meteorological information and data are available but no special additional measurements. First, the uncertainty arising only from the measurement uncertainties of the meteorological data is determined. Here, simulations show that uncertainties between 0.4 and 2 K due to the uncertainty of just one of the meteorological input parameters may be expected. We then analyse the determination accuracy when not all radiation data are available and modelling of the missing data is required. Since radiative transfer models require a lot of information that is usually not available, we concentrate only on the determination accuracy achievable with empirical models. The simulations show that uncertainties in the calculation of the diffuse irradiance may lead to Tmrt uncertainties of up to ±2.9 K. If long-wave radiation is missing, we may expect an uncertainty of ±2 K. If modelling of diffuse radiation and of longwave radiation is used for the calculation of Tmrt, we may then expect a determination uncertainty of ±3 K. If all radiative fluxes are modelled based on synoptic observation, the uncertainty in Tmrt is ±5.9 K. Because Tmrt is only one of the four input data required in the calculation of UTCI, the uncertainty in UTCI due to the uncertainty in radiation fluxes is less than ±2 K. The UTCI uncertainties due to uncertainties of the four meteorological input values are not larger than the 6 K reference intervals of the UTCI scale, which means that UTCI may only be wrong by one UTCI scale. This uncertainty may, however, be critical at the two temperature extremes, i.e. under extreme hot or extreme cold conditions.
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Regulação da Temperatura Corporal , Clima , Algoritmos , Humanos , Conceitos Meteorológicos , Modelos Biológicos , Luz Solar , TemperaturaRESUMO
Despite substantial reductions in anthropogenic emissions of nitrogen oxides (NO x ) and non-methane volatile organic compounds (NMVOCs) in Austria over the 30 year time period 1990-2019, summertime surface ozone (O3) concentrations still exceed frequently and over wide areas the ozone maximum 8 hour mean target value for the protection of human health. We present a detailed analysis of in situ observations of O3 and NO x to (1) disentangle the main processes propelling O3 formation such as precursor emissions and meteorology and (2) quantify the impact of NO x reductions and (3) estimate the effect of climate warming. The temperature sensitivity of surface O3 production is assessed separately for NO x and VOC limited regimes. The temperature sensitivity of ozone increases with temperature in spring and summer. On average, the evaluated absolute values of the sensitivities are a factor of 2.5 larger in summer than in spring. The analysis of ambient O3 burdens during hot summers indicates that rising temperatures in a warming climate might largely offset the benefit of future emission reductions. MAX-DOAS formaldehyde (HCHO) measurements in Vienna from 2017 to 2019 are used as a proxy for VOC emissions. The seasonal and the temperature dependence of the observed HCHO mixing ratios indicate that biogenic VOCs (BVOCs) are the dominant source of hydrocarbons in the urban setting during the ozone season. The result agrees well with VOC emission estimates that show BVOCs to be the dominant VOC source in Austria since the early 2000s. Accordingly, anthropogenic NO x emission reductions remain, outside of urban cores, the most effective instrument for policymakers to lower surface ozone concentrations in the short term.
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The only way to cure leukemia is by cooperative research. To optimize research, the European LeukemiaNet integrates 105 national leukemia trial groups and networks, 105 interdisciplinary partner groups and about 1,000 leukemia specialists from 175 institutions. They care for tens of thousands of leukemia patients in 33 countries across Europe. Their ultimate goal is to cure leukemia. Since its inception in 2002, the European LeukemiaNet has steadily expanded and has unified leukemia research across Europe. The European LeukemiaNet grew from two major roots: 1) the German Competence Network on Acute and Chronic Leukemias; and 2) the collaboration of European Investigators on Chronic Myeloid Leukemia. The European LeukemiaNet has improved leukemia research and management across Europe. Its concept has led to funding by the European Commission as a network of excellence. Other sources (European Science Foundation; European LeukemiaNet-Foundation) will take over when the support of the European Commission ends.
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Pesquisa Biomédica/organização & administração , Leucemia , Oncologia/organização & administração , Europa (Continente) , Humanos , Cooperação Internacional , Sociedades Médicas/organização & administraçãoRESUMO
The atmospheric concentration of well-mixed greenhouse gases has drastically increased since 1850. The prime cause for this increase is anthropogenic activity, particularly the burning of fossil fuels. As a consequence of the changing atmospheric composition, we observe a net positive radiative forcing, which manifests in global warming. The global mean surface temperature has increased since the preindustrial by about 1.0 °C. Under the assumption of continued greenhouse gas emissions, climate models project a temperature increase between 3.7 °C and 4.8 °C until 2100 (compared to the 1850-1900 mean). The assessment reports of the Intergovernmental Panel on Climate Change detail the catastrophic consequences of global warming of such extent for both ecosystems and mankind. As a consequence, the Paris Agreement aims to limit global warming to below 2 °C, ideally 1.5 °C, when compared to the preindustrial. To achieve this goal, fast and ambitious emission controls are required, reaching net zero emission by 2050 at the latest. Examining the global greenhouse gas emissions of recent decades, it becomes obvious how far away we are at present from reaching this goal. Also, the currently determined national contributions for emission reduction do not suffice to meet the 1.5 °C target. Thus, it is of uttermost importance to raise the global ambition in climate protection. The 1.5 °C target can still be reached, however, the time to set the required measures will expire within this decade.
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BACKGROUND: Expression of CD56 has been associated with poor prognosis in acute myeloid leukemia and aggressive lymphoma. DESIGN AND METHODS: We analyzed the impact of CD56 expression in a cohort of 452 newly diagnosed adult T-cell acute lymphoblastic leukemia (T-ALL) patients; clinical data were available for 306 patients. Treatment was according to the GMALL study protocols 06/99 and 07/03 stipulating stratification into standard (thymic T-ALL) and high risk (pre- and mature T-ALL) groups. RESULTS: CD56 expression was detected in 63/452 (13.9%) patients. CD56(+) T-ALL were predominantly of non-thymic (pre-T 35%, mature 41%) immunophenotypic subtypes, whereas 53% of the CD56(-) cases were thymic T-ALL (p=0.00002). CD13, CD33, CD34 and HLA-DR were significantly more frequently expressed. A clonal T-cell receptor rearrangement was detected in 22/23 CD56(+) ALL. No major clinical differences were observed at presentation. Treatment of CD56(+) ALL resulted in a lower rate of complete remissions (70% vs. 88%) (p=0.001) and a higher rate of resistant disease (21% vs. 8%) (p=0.004). CD56 expression had no significant influence on overall (48% vs. 59%) and disease free survival (67% vs. 57%) at three years. CONCLUSIONS: CD56 is expressed on a subset of adult T-ALL with distinct immunophenotypical features and higher resistance to therapy. Most CD56(+) ALL were treated in the high-risk arm of the GMALL study protocols owing to their non-thymic phenotype. Thus after risk adapted treatment a prognostic impact of CD56 expression was not detectable.
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Antígeno CD56 , Resistencia a Medicamentos Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Adolescente , Adulto , Idoso , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Prognóstico , Indução de Remissão/métodos , Análise de Sobrevida , Adulto JovemRESUMO
In addition to RB1 gene mutations, retinoblastomas frequently show gains of 1q and 6p and losses of 16q. To identify suppressor genes on 16q, we analyzed 22 short tandem repeat loci in 58 patients with known RB1 mutations. A subset of tumors was also investigated by conventional and matrix comparative genomic hybridization. In 40 of 58 (69%) tumors, we found no loss of heterozygosity (LOH) at any 16q marker. LOH was detected in 18 of 58 (31%) tumors, including five with allelic imbalance at some markers. In one tumor LOH was only observed at 16q24. As the parental origin of allele loss was unbiased, an imprinted locus is unlikely to be involved. Analysis of gene expression by microarray hybridization and quantitative RT real-time PCR did not identify a candidate suppressor in 16q24. Cadherin 13 (CDH13), CBFA2T3, and WFDC1, which are candidate suppressors in other tumor entities with 16q24 loss, did not show loss of expression. In addition, mutation and methylation analysis showed no somatic alteration of CDH13. Results in all tumors with chromosome 16 alterations define a single minimal deleted region of 5.7 Mb in the telomeric part of 16q24 with the centromeric boundary defined by retention of heterozygosity for a single nucleotide variant in exon 10 of CDH13 (Mb 82.7). Interestingly, clinical presentation of tumors with and without 16q alterations was distinct. Specifically, almost all retinoblastomas with 16q24 loss showed diffuse intraocular seeding. This suggests that genetic alterations in the minimal deleted region are associated with impaired cell-to-cell adhesion.