Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing

Ruxolitinib, an oral JAK1 and JAK2 inhibitor, is approved in the US for patients with intermediate or high-risk myelofibrosis (MF), a chronic neoplasm associated with aberrant myeloproliferation, progressive bone marrow fibrosis, splenomegaly, and burdensome symptoms. Phase III clinical studies have shown that ruxolitinib reduces splenomegaly and alleviates MF-related symptoms, with concomitant improvements in quality of life measures, for the overwhelming majority of treated patients. In addition, ruxolitinib provided an overall survival advantage as compared with either placebo or what was previously considered best available therapy in the two phase III studies. The most common adverse events with ruxolitinib treatment include dose-dependent anemia and thrombocytopenia, which are expected based on its mechanism of action. Experience from the phase III studies shows that these hematologic events can be managed effectively with dose modifications, temporary treatment interruptions, as well as red blood cell transfusions in the case of anemia and, importantly, are rarely cause for permanent treatment discontinuation. This review summarizes data supporting appropriate individualized patient management through careful monitoring of blood counts and dose titration as needed in order to maximize treatment benefit

Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results

Glasdegib is a Hedgehog pathway inhibitor. This ongoing, open-label, phase 2 study (NCT01546038) evaluated glasdegib plus cytarabine/daunorubicin in patients with untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS). Patients received glasdegib 100 mg orally, once daily in continuous 28-day cycles from day -3, with intravenous cytarabine 100 mg/

Occurrence of the Phoronid Phoronopsis albomaculata in Cocos Island, Costa Rica.

v. ill. 23 cm.QuarterlyThe phoronid Phoronopsis albomaculata was collected in subtidal (28– 35 m) sandy sediments in Bahı´a Chatham during a benthic survey designed to describe the biota of Cocos Island (Isla del Coco), Costa Rica, a national park and Human Heritage Site. Occurrence of this widespread species in Cocos Island is the first report of a phoronid for Costa Rican waters and is the second locality recorded for the eastern Pacific. Taxonomically significant characters (presence of an epidermal collar, extent of coiling of lophophore and nephridia) are discussed. Comparisons are made between depth and abundance of this species from Cocos Island and results of previous studies

Quantificação energética de arranque de uma instalação AVAC

A transposição da Diretiva n.º 2002/91/CE - Parlamento Europeu e do Conselho (de 16 de Dezembro), para a legislação nacional resultou no Sistema de Certificação Energética - Decretos-lei n.º 78/2006, 79/2006 e 80/2006, de 4 de Abril. Estes definem as regras e parâmetros de dimensionamento dos sistemas Ativos de Climatização em Edifícios, pelos quais os dimensionamentos se regem, orientam e cumprem. Definem igualmente as características de utilização das instalações, os parâmetros de funcionamento, as tecnologias e soluções a empregar, propondo-se a limitar o custo energético da solução. No entanto, a regulamentação quantifica somente as cargas em regime estacionário, não quantificando o custo de "prontidão" de cada um dos sistemas e, mais importante ainda, o tempo que os sistemas necessitam para atingir as condições requeridas, quando no regime transiente de arranque. Neste estudo serão comparados dois sistemas distintos de climatização, relativamente ao período transiente de arranque, respectivo consumo energético e correspondente eficiência energética, determinando-se desse modo a adequabilidade de cada sistema a cada aplicação específica

Current Challenges and Applications for Adaptive User Interfaces

Non

Surface Structures Involved in Plant Stomata and Leaf Colonization by Shiga-Toxigenic Escherichia Coli O157:H7

Shiga-toxigenic Escherichia coli (STEC) O157:H7 uses a myriad of surface adhesive appendages including pili, flagella, and the type 3 secretion system (T3SS) to adhere to and inflict damage to the human gut mucosa. Consumption of contaminated ground beef, milk, juices, water, or leafy greens has been associated with outbreaks of diarrheal disease in humans due to STEC. The aim of this study was to investigate which of the known STEC O157:H7 adherence factors mediate colonization of baby spinach leaves and where the bacteria reside within tainted leaves. We found that STEC O157:H7 colonizes baby spinach leaves through the coordinated production of curli, the E. coli common pilus, hemorrhagic coli type 4 pilus, flagella, and T3SS. Electron microscopy analysis of tainted leaves revealed STEC bacteria in the internal cavity of the stomata, in intercellular spaces, and within vascular tissue (xylem and phloem), where the bacteria were protected from the bactericidal effect of gentamicin, sodium hypochlorite or ozonated water treatments. We confirmed that the T3S escN mutant showed a reduced number of bacteria within the stomata suggesting that T3S is required for the successful colonization of leaves. In agreement, non-pathogenic E. coli K-12 strain DH5α transformed with a plasmid carrying the locus of enterocyte effacement (LEE) pathogenicity island, harboring the T3SS and effector genes, internalized into stomata more efficiently than without the LEE. This study highlights a role for pili, flagella, and T3SS in the interaction of STEC with spinach leaves. Colonization of plant stomata and internal tissues may constitute a strategy by which STEC survives in a nutrient-rich microenvironment protected from external foes and may be a potential source for human infection

Impacto de la altitud sobre la mortalidad por Covid-19 en Colombia: un estudio transversal

Objective. To estimate the proportion of deaths in confirmed cases according to altitude categories (low, medium, and high), and to evaluate a possible association between altitude and COVID-19 mortality in Colombia during the first two waves of the pandemic. Methods. Cross-sectional, analytical study. Adults residing in Colombia during 2020, with microbiological confirmation of SARS-CoV-2 infection were included. We calculated CFR using a binomial confidence interval, dividing altitude in three categories. We also performed a logistic regression model to evaluate the association between altitude and COVID-19 mortality. Results. Data on confirmed cases of COVID-19 during the period from March 06, 2020, to December 15, 2020, reported in 1,112 municipalities in Colombia were analyzed. A total of 994,738 confirmed cases were reported, including 32,034 deaths (0,03%). The mean age of cases was 39,8 years and 504,476 (50,4%) were male. The altitude range varied between 0 m to 3,350 m. The CFR was 0,042 (CI 95% 0,042 - 0,043; p value <0.001); 0,027 (CI 95% 0,027 - 0,028; p value <0.001) and 0,026 (CI 95% 0,025 - 0.026; p value <0.001) for low, middle, and high altitude, respectively. We found that for each km increase in altitude, the probability of dying from COVID-19 decreases by 20% (OR 0.8; 95% CI 0.785 - 0.815; p value <0.001), controlled by biological sex, age and number of inhabitants per municipality. Conclusions. Our results demonstrate that the altitude is a potential protective factor against COVID-19 mortality according to data from a Colombian population during the first two waves of the epidemic.Objetivo. Estimar la proporción de muertes en los casos confirmados según las categorías de altitud (baja, media y alta) y evaluar una posible asociación entre el grado de altitud y la mortalidad por COVID-19 en Colombia, durante las dos primeras olas de la epidemia. Métodos. Estudio de corte transversal, analítico. La población de estudio fueron adultos residentes en Colombia durante 2020, con confirmación microbiológica de infección por SARS-CoV-2. Se calculó la tasa de letalidad utilizando un intervalo de confianza binomial, dividiendo la altitud en tres categorías. También se realizó un modelo de regresión logística para evaluar la asociación entre la altitud y la mortalidad por COVID-19. Resultados. Se analizaron los datos de casos confirmados de COVID-19 durante el periodo comprendido entre el 06 de marzo de 2020 y el 15 de diciembre de 2020, reportados en 1.112 municipios de Colombia. Se notificaron un total de 994.738 casos confirmados, incluidas 32.034 muertes (0,03%). La edad media de los casos fue de 39,8 años y 504.476 (50,4%) eran varones. El rango de altitud varió entre 0 m y 3.350 m. La tasa de letalidad estimada fue de 0,042 (IC 95% 0,042 - 0,043; valor de p <0,001); 0,027 (IC 95% 0,027 - 0,028; valor de p <0,001) y 0,026 (IC 95% 0,025 - 0,026; valor de p <0,001) para altitud baja, media y alta, respectivamente. Encontramos que, por cada km de aumento de altitud, la probabilidad de morir por COVID-19 disminuye un 20% (OR 0,8; IC 95% 0,785 - 0,815; valor de p <0,001), controlando por variables como sexo biológico, edad y número de habitantes por municipio. Conclusiones. Nuestros resultados demuestran que la altitud es un potencial factor protector frente a la mortalidad por COVID-19 de acuerdo con datos de población colombiana, durante las primeras dos olas de la pandemia