Some of the early events underlying Th2 cell maturation and susceptibility to Leishmania major infection in BALB/c mice.

The first experimental evidence for the development of polarized CD4+ Th1 and Th2 responses in vivo has been obtained using the murine model of infection with Leishmania major, an intracellular parasite of macrophages in their vertebrate host. Genetically determined resistance and susceptibility to infection with this parasite have been clearly demonstrated to result from the development of polarized Th1 and Th2 responses, respectively. Using this model system, the dominant role of cytokines in the induction of polarized CD4+ responses has been validated in vivo. The requisite role of IL-4 in mediating both Th2 differentiation and susceptibility to infection in BALB/c mice has directed interest towards the search for evidence of IL-4 production early after infection and identification of its cellular source. We have been able to demonstrate a burst of IL-4 production in susceptible BALB/c mice within the first day of infection with L. major and could establish that this rapidly produced IL-4 instructed Th2 lineage commitment of subsequently activated CD4+ T cells and stabilized this commitment by downregulating IL-12 Rbeta2 chain expression, resulting in susceptibility to infection. Strikingly, this early IL-4 response to infection resulted from the cognate recognition of a single epitope in a distinctive antigen, LACK, from this complex microorganism by a restricted population of CD4+ T cells that express Vbeta4-Valpha8 T cell receptors.

Reação de híbridos comerciais de milho às ferrugens polissora e tropical

Os objetivos deste trabalho foram avaliar o nível de resistência de oito híbridos comerciais de milho aos patógenos Puccinia polysora Underw e Physopella zeae (Mains) Cummins e Ramachar, e comparar a eficiência dos métodos da área abaixo da curva de progresso da doença (AACPD) e dos parâmetros de estabilidade fenotípica, na avaliação dessa resistência. Em quatro ambientes nas regiões Sudeste e Centro-Oeste do Brasil foram realizadas cinco avaliações da severidade das doenças, em intervalos de dez dias a partir dos 60 dias após a semeadura, utilizando uma escala diagramática com notas. Os parâmetros de estabilidade fenotípica estudados foram o coeficiente de regressão linear (b) entre a época de avaliação (x) e a severidade da doença (y) e o coeficiente de determinação (R²). No caso de P. polysora, ambos os métodos utilizados mostraram-se eficientes na discriminação do nível de resistência dos híbridos, permitindo a classificação de modo semelhante. Quanto a P. zeae, não houve boa concordância entre os dois métodos, especialmente porque a discriminação do nível de resistência entre híbridos não foi expressiva. Os híbridos mais resistentes a P. polysora foram Z 8392, C 909 e C 333, e os mais suscetíveis, P 3069, AG 9012 e C 956. Os destaques, em termos de resistência a P. zeae, foram C 909 e C 333, e os híbridos mais suscetíveis, P 3069 e AG 9012.

Initial and Extended Use of Femoral Versus Nonfemoral Double-Lumen Vascular Catheters and Catheter-Related Infection During Continuous Renal Replacement Therapy.

BACKGROUND: The risk of catheter-related infection or bacteremia, with initial and extended use of femoral versus nonfemoral sites for double-lumen vascular catheters (DLVCs) during continuous renal replacement therapy (CRRT), is unclear. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Critically ill patients on CRRT in a combined intensive care unit of a tertiary institution. FACTOR: Femoral versus nonfemoral venous DLVC placement. OUTCOMES: Catheter-related colonization (CRCOL) and bloodstream infection (CRBSI). MEASUREMENTS: CRCOL/CRBSI rates expressed per 1,000 catheter-days. RESULTS: We studied 458 patients (median age, 65 years; 60% males) and 647 DLVCs. Of 405 single-site only DLVC users, 82% versus 18% received exclusively 419 femoral versus 82 jugular or subclavian DLVCs, respectively. The corresponding DLVC indwelling duration was 6±4 versus 7±5 days (P=0.03). Corresponding CRCOL and CRBSI rates (per 1,000 catheter-days) were 9.7 versus 8.8 events (P=0.8) and 1.2 versus 3.5 events (P=0.3), respectively. Overall, 96 patients with extended CRRT received femoral-site insertion first with subsequent site change, including 53 femoral guidewire exchanges, 53 new femoral venipunctures, and 47 new jugular/subclavian sites. CRCOL and CRBSI rates were similar for all such approaches (P=0.7 and P=0.9, respectively). On multivariate analysis, CRCOL risk was higher in patients older than 65 years and weighing >90kg (ORs of 2.1 and 2.2, respectively; P<0.05). This association between higher weight and greater CRCOL risk was significant for femoral DLVCs, but not for nonfemoral sites. Other covariates, including initial or specific DLVC site, guidewire exchange versus new venipuncture, and primary versus secondary DLVC placement, did not significantly affect CRCOL rates. LIMITATIONS: Nonrandomized retrospective design and single-center evaluation. CONCLUSIONS: CRCOL and CRBSI rates in patients on CRRT are low and not influenced significantly by initial or serial femoral catheterizations with guidewire exchange or new venipuncture. CRCOL risk is higher in older and heavier patients, the latter especially so with femoral sites.

Adaptabilidade e estabilidade de cultivares e híbridos de milho no Nordeste brasileiro no ano agrícola de 1998

Durante o ano agrícola de 1998, na Região Nordeste do Brasil, foram realizados experimentos em rede, em blocos casualizados com três repetições, envolvendo a avaliação de 25 cultivares (cultivares e populações) e de 30 híbridos de milho em dezenove e dezesseis ambientes, respectivamente, objetivando conhecer adaptabilidade e estabilidade dessas cultivares para fins de recomendação. Os híbridos apresentaram maiores rendimentos, em média, 21,4% mais que as cultivares. Nos ensaios envolvendo cultivares e populações, o híbrido Cargill 909, utilizado como testemunha, teve um rendimento superior, tanto nos ambientes desfavoráveis quanto nos favoráveis. As cultivares AL 30, BR 5028, BR 106, BR 5011, BR 5033, Sintético Dentado, Sintético Duro e a população CMS 50 expressaram boa adaptação e estabilidade de produção no Nordeste brasileiro. Nos ensaios envolvendo híbridos, Dina 1000, Cargill 333 B, Dina 270, Braskalb XL 360, Master, AG 1051, AG 4051 e Pioneer 3041 apresentaram maior adaptação com estabilidade de produção nos ambientes considerados. Para recomendação específica a ambientes favoráveis destacaram-se os híbridos AG 4051 e Pioneer X 1296 B. Apesar de não se encontrarem híbridos com adaptação específica a ambientes desfavoráveis, a recomendação de materiais com maiores rendimentos nesses ambientes é de interesse para o agricultor, a exemplo do Dina 1000, Cargill 333 B e Braskalb XL 360.

Expected impact of applying new 2013 AHA/ACC cholesterol guidelines criteria on the recommended lipid target achievement after acute coronary syndromes.

BACKGROUND: 2013 AHA/ACC guidelines on the treatment of cholesterol advised to tailor high-intensity statin after ACS, while previous ATP-III recommended titration of statin to reach low-density lipoprotein cholesterol (LDL-C) targets. We simulated the impact of this change of paradigm on the achievement of recommended targets. METHODS: Among a prospective cohort study of consecutive patients hospitalized for ACS from 2009 to 2012 at four Swiss university hospitals, we analyzed 1602 patients who survived one year after recruitment. Targets based on the previous guidelines approach was defined as (1) achievement of LDL-C target < 1.8 mmol/l, (2) reduction of LDL-C ≥ 50% or (3) intensification of statin in patients who did not reach LDL-C targets. Targets based on the 2013 AHA/ACC guidelines approach was defined as the maximization of statin therapy at high-intensity in patients aged ≤75 years and moderate- or high-intensity statin in patients >75 years. RESULTS: 1578 (99%) patients were prescribed statin at discharge, with 1120 (70%) at high-intensity. 1507 patients (94%) reported taking statin at one year, with 909 (57%) at high-intensity. Among 482 patients discharged with sub-maximal statin, intensification of statin was only observed in 109 patients (23%). 773 (47%) patients reached the previous LDL-C targets, while 1014 (63%) reached the 2013 AHA/ACC guidelines targetsone year after ACS (p value < 0.001). CONCLUSION: The application of the new 2013 AHA/ACC guidelines criteria would substantially increase the proportion of patients achieving recommended lipid targets one year after ACS. Clinical trial number, NCT01075868.

Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.

Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ∼110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.

Hardy’s inequalities for monotone functions on partly ordered measure spaces

We characterize the weighted Hardy inequalities for monotone functions in Rn +. In dimension n = 1, this recovers the standard theory of Bp weights. For n > 1, the result was previously only known for the case p = 1. In fact, our main theorem is proved in the more general setting of partly ordered measure spaces.

In situ RHAMM protein expression in acute myeloid leukemia blasts suggests poor overall survival.

Treatment options for patients with high-risk acute myeloid leukemia (AML) include high-dose chemotherapy regimens in combination with allogeneic hematopoietic stem cell transplantation, which takes advantage of the donor T-cell-mediated graft-versus-leukemia effect. Together with beneficial responses observed in assays targeted at leukemia-associated antigens (LAA), this encouraged research on cancer vaccines and adoptive cellular therapies in AML. The receptor for hyaluronic acid-mediated motility (RHAMM, CD168) was identified as one of the most promising LAA in AML. Thus far, little is known about in situ expression in leukemic bone marrow blasts or the prognostic role of RHAMM and its interaction partners in AML. We immunohistochemically analyzed the expression and prognostic significance of RHAMM on trephine bone marrow biopsies from 71 AML cases that had been evaluated for cytogenetics and presence of FLT3-internal tandem duplications and NPM1 mutations. Fifty-five patients (77%) were treated with curative intent, while 16 (23%) received the most appropriate supportive care. Twenty of 71 (28%) AML cases were considered RHAMM+. Receiver operating characteristic curves showed significant discriminatory power considering overall survival (OS) in AML patients treated curatively for RHAMM (p = 0.015). Multivariable analysis revealed that expression of RHAMM in >5% of leukemic blasts identifies a subgroup of curatively treated cases with adverse OS independent of failures to achieve complete remission. RHAMM not only represents a promising LAA with specific T-cell responses in AML but, if assessed in situ on blasts, also a probable prognostic factor.

Tuomioistuinten rutiinit ja prosessioikeus

English summary: Court routine and procedural law (s. 909)

Lahjoitukset yleishyödyllisen yhteisön varainhankintakeinona : rahankeräyssääntelyä ja veropolitiikkaa

English summary: Donation as a revenue source for non-profit organisations - on the regulation of fundraising campaigns and tax policy (s. 909-910)

Results of An International Study of Quantitative BCR/ABL Assays Using Defined RNA Samples

Molecular monitoring of BCR/ABL transcripts by real time quantitative reverse transcription PCR (qRT-PCR) is an essential technique for clinical management of patients with BCR/ABL-positive CML and ALL. Though quantitative BCR/ABL assays are performed in hundreds of laboratories worldwide, results among these laboratories cannot be reliably compared due to heterogeneity in test methods, data analysis, reporting, and lack of quantitative standards. Recent efforts towards standardization have been limited in scope. Aliquots of RNA were sent to clinical test centers worldwide in order to evaluate methods and reporting for e1a2, b2a2, and b3a2 transcript levels using their own qRT-PCR assays. Total RNA was isolated from tissue culture cells that expressed each of the different BCR/ABL transcripts. Serial log dilutions were prepared, ranging from 100 to 10-5, in RNA isolated from HL60 cells. Laboratories performed 5 independent qRT-PCR reactions for each sample type at each dilution. In addition, 15 qRT-PCR reactions of the 10-3 b3a2 RNA dilution were run to assess reproducibility within and between laboratories. Participants were asked to run the samples following their standard protocols and to report cycle threshold (Ct), quantitative values for BCR/ABL and housekeeping genes, and ratios of BCR/ABL to housekeeping genes for each sample RNA. Thirty-seven (n=37) participants have submitted qRT-PCR results for analysis (36, 37, and 34 labs generated data for b2a2, b3a2, and e1a2, respectively). The limit of detection for this study was defined as the lowest dilution that a Ct value could be detected for all 5 replicates. For b2a2, 15, 16, 4, and 1 lab(s) showed a limit of detection at the 10-5, 10-4, 10-3, and 10-2 dilutions, respectively. For b3a2, 20, 13, and 4 labs showed a limit of detection at the 10-5, 10-4, and 10-3 dilutions, respectively. For e1a2, 10, 21, 2, and 1 lab(s) showed a limit of detection at the 10-5, 10-4, 10-3, and 10-2 dilutions, respectively. Log %BCR/ABL ratio values provided a method for comparing results between the different laboratories for each BCR/ABL dilution series. Linear regression analysis revealed concordance among the majority of participant data over the 10-1 to 10-4 dilutions. The overall slope values showed comparable results among the majority of b2a2 (mean=0.939; median=0.9627; range (0.399 - 1.1872)), b3a2 (mean=0.925; median=0.922; range (0.625 - 1.140)), and e1a2 (mean=0.897; median=0.909; range (0.5174 - 1.138)) laboratory results (Fig. 1-3)). Thirty-four (n=34) out of the 37 laboratories reported Ct values for all 15 replicates and only those with a complete data set were included in the inter-lab calculations. Eleven laboratories either did not report their copy number data or used other reporting units such as nanograms or cell numbers; therefore, only 26 laboratories were included in the overall analysis of copy numbers. The median copy number was 348.4, with a range from 15.6 to 547,000 copies (approximately a 4.5 log difference); the median intra-lab %CV was 19.2% with a range from 4.2% to 82.6%. While our international performance evaluation using serially diluted RNA samples has reinforced the fact that heterogeneity exists among clinical laboratories, it has also demonstrated that performance within a laboratory is overall very consistent. Accordingly, the availability of defined BCR/ABL RNAs may facilitate the validation of all phases of quantitative BCR/ABL analysis and may be extremely useful as a tool for monitoring assay performance. Ongoing analyses of these materials, along with the development of additional control materials, may solidify consensus around their application in routine laboratory testing and possible integration in worldwide efforts to standardize quantitative BCR/ABL testing.

Indicadores de calidad de la producción en la Web of Science de diez profesores del Área de Personalidad, Evaluación y Tratamiento Psicológico: aportaciones adicionales al estudio de Olivas-Ávila y Musi-Lechuga

Los rankings de productividad científica resultan cada vez más relevantes, tanto a nivel individual como institucional. Garantizar que se basan en información confiable y exhaustiva es, por tanto, importante. Este estudio indica que la posición de los individuos en esa clase de ranking puede cambiar sustancialmente cuando se consideran diversos indicadores bibliométricos internacionalmente reconocidos. Se usa, como ilustración, el caso de los diez profesores del área de ‘Personalidad, Evaluación y Tratamiento Psicológico’ consignados en el reciente análisis de Olivas-Ávila y Musi-Lechuga (Psicothema 2010. Vol. 22, nº 4, pp. 909-916).

Crescimento do abacaxizeiro 'vitória' irrigado sob diferentes densidades populacionais, fontes e doses de nitrogênio

Com o objetivo de avaliar o crescimento do abacaxizeiro 'Vitória' irrigado, submetido ao aumento da densidade populacional, e doses de N na região norte de Minas Gerais, foi instalado um experimento em esquema fatorial 5 x 4 x 4, correspondendo a cinco doses de N (0; 5; 10; 15 e 20 g planta-1), quatro populações de plantas (51.282; 76.923; 90.909 e 126.984 plantas ha-1) e quatro épocas de avaliação (270; 360; 450 e 540 dias após o plantio - DAP), utilizando ureia ou esterco bovino como fonte de N. Aos 540 dias após o plantio - DAP (época de indução floral), foi avaliado o efeito das fontes de N por meio do fatorial 2 x 5 x 4, que consistiu em : duas fontes N (ureia e esterco bovino), cinco doses de N e quatro populações de plantas, conforme estudo anterior. Utilizou-se o delineamento em blocos casualizados, com três repetições, com mudas micropropagadas da cultivar Vitória. Avaliaram-se as características de crescimento da planta (número de folhas emitidas, comprimento e peso da folha "D" e diâmetro do caule), além do peso dos frutos com e sem coroa no final do cultivo. Não foi observada interação entre densidade de plantio, doses de N e dias após o plantio (DAP). O aumento da densidade de plantio reduziu o diâmetro do caule do abacaxizeiro, no entanto não interferiu no peso dos frutos, indicando a possibilidade de aumento da população de plantas para o incremento da produtividade. A utilização de ureia como fonte de N promoveu maior crescimento e peso dos frutos do abacaxizeiro. A utilização de doses de N na forma de ureia e esterco promoveu maior crescimento do abacaxizeiro e incremento linearmente no peso dos frutos, indicando a dose de 20 g planta-1 na forma de ureia, como recomendação de adubação nitrogenada para o cultivo do abacaxizeiro 'Vitória' irrigado.