Summary and Highlights of the SPARC-Reanalysis Intercomparison Project

The climate research community uses global atmospheric reanalysis data sets to understand a wide range of processes and variability in the atmosphere; they are a particularly powerful tool for studying phenomena that cannot be directly observed. Different reanalyses may give very different results for the same diagnostics. The Stratosphere troposphere Processes And their Role in Climate (SPARC) Reanalysis Intercomparison Project (S-RIP) is a coordinated activity to compare key diagnostics that are important for stratospheric processes and their tropospheric connections among available reanalyses. S-RIP has been identifying differences among reanalyses and their underlying causes, providing guidance on appropriate usage of reanalysis products in scientific studies (particularly those of relevance to SPARC), and contributing to future improvements in the reanalysis products by establishing collaborative links between reanalysis centres and data users. S-RIP emphasizes diagnostics of the upper troposphere, stratosphere, and lower mesosphere. The draft S-RIP final report is expected to be completed in 2018. This poster gives a summary of the S-RIP project and presents highlights including results on the Brewer-Dobson circulation, stratosphere/troposphere dynamical coupling, the extra-tropical upper troposphere / lower stratosphere, the tropical tropopause layer, the quasi-biennial oscillation, lower stratospheric polar processing, and the upper stratosphere/lower mesosphere

Spectral variability in high frequency in sea level and atmospheric pressure on Buenos Aires Coast, Argentina

Abstract There are some observational evidences which support that atmospheric gravity waves constitute an efficient forcing for meteorological tsunamis (meteotsunamis) along the coast of Buenos Aires, Argentina. Meteotsunamis and atmospheric gravity waves, which propagate simultaneously on the sea surface and the atmosphere, respectively, are typical examples of non-stationary geophysical signals. The variability of meteotsunamis and atmospheric gravity waves recorded at Mar del Plata was investigated in this paper. Results obtained in this work reinforce the idea of a cause (atmospheric gravity waves) effect (meteotsunami) relationship, because wavelet spectra obtained from both signals resulted quite similar. However, several very short episodes of mod-erate/low activity of atmospheric gravity waves were detected without detecting meteotsunami activity. On the other hand, it was found that atmospheric gravity wave spectral energy can appear in the wavelets as a single or multiple burst as relatively long and irregular events or as regular wave packets. Results obtained in this paper provide original spectral data about atmospheric gravity waves along the coast of Buenos Aires. This information is useful to be included in realistic numerical models in order to investigate the genesis of this complex atmosphere-ocean interaction

Climate warming and decreasing total column ozone over the Tibetan Plateau during winter and spring

The long-term trends of the total column ozone (TCO) over the Tibetan Plateau (TP) and factors responsible for the trends are analysed in this study using various observations and a chemistry–climate model (CCM). The results indicate that the total column ozone low (TOL) over the TP during winter and spring is deepening over the recent decade, which is opposite to the recovery signal in annual mean TCO over the TP after mid-1990s. The TOL intensity is increasing at a rate of 1.4 DU/decade and the TOL area is extending with 50,000 km2/decade during winter for the period 1979–2009. The enhanced transport of ozone-poor air into the stratosphere and elevated tropopause due to the rapid and significant warming over the TP during winter reduce ozone concentrations in the upper troposphere and lower stratosphere and hence lead to the deepening of the TOL. Based on the analysis of the multiple regression model, the thermal dynamical processes associated with the TP warming accounts for more than 50% of TCO decline during winter for the period 1979–2009. The solar variations during 1995–2009 further enlarge ozone decreases over the TP in the past decade. According to the CCM simulations, the increases in NOx emissions in East Asia and global tropospheric N2O mixing ratio for the period 1979–2009 contribute to no more than 20% reductions in TCO during this period

Numerical simulation of wind waves on the Río de la Plata: evaluation of four global atmospheric databases

The performance of NCEP/NCAR I, NCEP/DOE II, JRA-25 and ERA-Interim global databases, implemented as atmospheric forcings of the SWAN model in the Río de la Plata region, was quantitatively tested by calculating the bias, the mean square root error, the determination coefficient and the slope of the line fitted between observed and simulated wave parameters (significant wave height, mean period and direction). Even though statistical estimators showed no evident differences for wave periods and directions some noticeable differences were observed for simulated significant wave heights depending on the forcing used. The lowest bias (0.22 m) was obtained when the SWAN model was forced by ERA-Interim. With regard to the mean square root errors, the lowest values were obtained when NCEP/NCAR I (0.16 m) and NCEP/DOE II (0.19 m) were used as forcing. In addition, the best slope for simulated heights (0.79) was obtained using NCEP/DOE II. Computed determination coefficients for heights, periods and directions were very similar (0.89-0.93) for all the simulations carried out in this study. Energetic and severe wave events were given special consideration. The most energetic wave episode recorded in the Río de la Plata mouth (24 August, 2005) was analyzed and discussed in particular. It was concluded that during energetic atmospheric conditions the best agreement is achieved by implementing NCEP/DOE II as forcing. In the light of these results it is concluded that NCEP/DOE II is the most suitable atmospheric forcing to simulate wave heights with the SWAN model in the Río de la Plata region.Na região do Rio de la Plata, o desempenho das reanálises globais do NCEP/NCAR I, NCEP/DOE II, JRA-25 e ERAInterim implementadas como forçantes atmosféricas do modelo SWAN foram quantitativamente acessados através do viés, erro quadrático médio, coeficiente de determinação e inclinação da reta. Estes índices foram obtidos dos parâmetros de ondas observados e simulados (alturas significativas de ondas, período principal e direção). Embora as estimativas estatísticas não mostrem diferenças evidentes para períodos e direções, algumas diferenças notáveis foram obtidas para altura de ondas simuladas, dependendo do vento utilizado. O menor viés para altura significativa (0.22 m) foi obtido quando o SWAM foi forçado com a ERAInterim, enquanto o NCEP/NCAR I (0.16 m) e NCEP/DOE II (0.19 m) forneceram menor erro quadrático médio. A melhor inclinação da reta entre simulação e observação de altura significativa (0.79) foi obtida usando NCEP/DOE II. No período de estudo, o maior episódio de onda registrado na boca do Río de la Plata foi analisado e discutido. Neste evento de condições atmosféricas energéticas o melhor ajuste foi alcançado utilizando os ventos do NCEP/DOE II como forçante. Conclui-se que a base de dados NCEP/DOE II é forçante atmosférica mais adequada para simular alturas significativas de ondas com o modelo SWAN na região estudada

Efficacy and safety of nilotinib as frontline treatment in elderly (> 65 years) chronic myeloid leukemia patients outside clinical trials

Here, we report real-world evidence on the safety and efficacy of nilotinib as a first-line treatment in elderly patients with chronic phase CML, treated in 18 Italian centers. Sixty patients aged > 65 years (median age 72 years (65-84)) were reported: 13 patients were older than 75 years. Comorbidities were recorded at baseline in 56/60 patients. At 3 months of treatment, all patients obtained complete hematological response (CHR), 43 (71.6%) an early molecular response (EMR), while 47 (78%) reached a complete cytogenetic response (CCyR). At last follow-up, 63.4% of patients still had a deep molecular response (MR4 or better), 21.6% reached MR3 as best response and 11.6% persisted without MR. Most patients (85%) started the treatment at the standard dose (300 mg BID), maintained at 3 months in 80% of patients and at 6 months in 89% of them. At the last median follow-up of 46.3 months, 15 patients discontinued definitively the treatment (8 due to side effects, 4 died for unrelated CML causes, 1 for failure, 2 were lost to follow-up). One patient entered in treatment-free remission. As to safety, 6 patients (10%) experienced cardiovascular events after a median time of 20.9 months from the start. Our data showed that nilotinib could be, as first-line treatment, effective and relatively safe even in elderly CML patients. In this setting, more data in the long term are needed about possible dose reduction to improve the tolerability, while maintaining the optimal molecular response

Mutational analysis of xenobiotic metabolizing genes (CYP1A1 and GSTP1) in sporadic head and neck cancer patients

CYP1A1 is the phase I enzyme that detoxifies the carcinogen or converts it into a more electrophilic form, metabolized by phase II enzymes like GSTP1. These detoxifying genes have been extensively studied in association with head and neck cancer (HNC) in different ethnic groups worldwide. The current study was aimed at screening genetic polymorphisms of genes CYP1A1 and GSTP1 in 388 Pakistani HNC patients and 150 cancer-free healthy controls, using PCR-SSCP. No already known variants of either gene were found, however a novel frameshift mutation due to insertion of T (g.2842_2843insT) was observed in the CYP1A1 gene. A statistically significant number (5.4%) of HNC cases, with the mean age of 51.75 (±15.7) years, presented this frameshift mutation in the conserved domain of CYP1A1. Another novel substitution mutation in was found in the GSTP1 gene, presenting TA instead of AG. The g.2848A > T polymorphism causes a leucine-to-leucine formation, whereas g.2849G > A causes alanine-to-threonine formation at amino acid positions 166 and 167, respectively. These exonic mutations were found in 9.5% of the HNC patients and in none of the controls. In addition, two intronic deletions of C (g.1074delC and g.1466delC) were also found in 11 patients with a mean age of 46.2 (±15.6) years. In conclusion, accumulation of mutations in genes CYP1A1 and GSTP1 appears to be associated with increased risk of developing HNC, suggesting that mutations in these genes may play a role in the etiology of head and neck cancer

Immunization of mice with the nef gene from Human Immunodeficiency Virus type 1: Study of immunological memory and long-term toxicology

<p>Abstract</p> <p>Background</p> <p>The human immunodeficiency virus type 1 (HIV-1) regulatory protein, Nef, is an attractive vaccine target because it is involved in viral pathogenesis, is expressed early in the viral life cycle and harbors many T and B cell epitopes. Several clinical trials include gene-based vaccines encoding this protein. However, Nef has been shown to transform certain cell types <it>in vitro</it>. Based on these findings we performed a long-term toxicity and immunogenicity study of Nef, encoded either by Modified Vaccinia virus Ankara or by plasmid DNA. BALB/c mice were primed twice with either DNA or MVA encoding Nef and received a homologous or heterologous boost ten months later. In the meantime, the Nef-specific immune responses were monitored and at the time of sacrifice an extensive toxicological evaluation was performed, where presence of tumors and other pathological changes were assessed.</p> <p>Results</p> <p>The toxicological evaluation showed that immunization with MVAnef is safe and does not cause cellular transformation or other toxicity in somatic organs.</p> <p>Both DNAnef and MVAnef immunized animals developed potent Nef-specific cellular responses that declined to undetectable levels over time, and could readily be boosted after almost one year. This is of particular interest since it shows that plasmid DNA vaccine can also be used as a potent late booster of primed immune responses. We observed qualitative differences between the T cell responses induced by the two different vectors: DNA-encoded nef induced long-lasting CD8⁺T cell memory responses, whereas MVA-encoded nef induced CD4⁺T cell memory responses. In terms of the humoral immune responses, we show that two injections of MVAnef induce significant anti-Nef titers, while repeated injections of DNAnef do not. A single boost with MVAnef could enhance the antibody response following DNAnef prime to the same level as that observed in animals immunized repeatedly with MVAnef. We also demonstrate the possibility to boost HIV-1 Nef-specific immune responses using the MVAnef construct despite the presence of potent anti-vector immunity.</p> <p>Conclusion</p> <p>This study shows that the nef gene vectored by MVA does not induce malignancies or other adverse effects in mice. Further, we show that when the nef gene is delivered by plasmid or by a viral vector, it elicits potent and long-lasting immune responses and that these responses can be directed towards a CD4⁺or a CD8⁺T cell response depending on the choice of vector.</p