Safety and immunogenicity of a chimpanzee adenovirus-vectored Ebola vaccine in healthy adults: a randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a study.

BACKGROUND: The ongoing Ebola outbreak led to accelerated efforts to test vaccine candidates. On the basis of a request by WHO, we aimed to assess the safety and immunogenicity of the monovalent, recombinant, chimpanzee adenovirus type-3 vector-based Ebola Zaire vaccine (ChAd3-EBO-Z). METHODS: We did this randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a trial at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Participants (aged 18-65 years) were randomly assigned (2:2:1), via two computer-generated randomisation lists for individuals potentially deployed in endemic areas and those not deployed, to receive a single intramuscular dose of high-dose vaccine (5 × 10(10) viral particles), low-dose vaccine (2·5 × 10(10) viral particles), or placebo. Deployed participants were allocated to only the vaccine groups. Group allocation was concealed from non-deployed participants, investigators, and outcome assessors. The safety evaluation was not masked for potentially deployed participants, who were therefore not included in the safety analysis for comparison between the vaccine doses and placebo, but were pooled with the non-deployed group to compare immunogenicity. The main objectives were safety and immunogenicity of ChAd3-EBO-Z. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02289027. FINDINGS: Between Oct 24, 2014, and June 22, 2015, we randomly assigned 120 participants, of whom 18 (15%) were potentially deployed and 102 (85%) were non-deployed, to receive high-dose vaccine (n=49), low-dose vaccine (n=51), or placebo (n=20). Participants were followed up for 6 months. No vaccine-related serious adverse events were reported. We recorded local adverse events in 30 (75%) of 40 participants in the high-dose group, 33 (79%) of 42 participants in the low-dose group, and five (25%) of 20 participants in the placebo group. Fatigue or malaise was the most common systemic adverse event, reported in 25 (62%) participants in the high-dose group, 25 (60%) participants in the low-dose group, and five (25%) participants in the placebo group, followed by headache, reported in 23 (57%), 25 (60%), and three (15%) participants, respectively. Fever occurred 24 h after injection in 12 (30%) participants in the high-dose group and 11 (26%) participants in the low-dose group versus one (5%) participant in the placebo group. Geometric mean concentrations of IgG antibodies against Ebola glycoprotein peaked on day 28 at 51 μg/mL (95% CI 41·1-63·3) in the high-dose group, 44·9 μg/mL (25·8-56·3) in the low-dose group, and 5·2 μg/mL (3·5-7·6) in the placebo group, with respective response rates of 96% (95% CI 85·7-99·5), 96% (86·5-99·5), and 5% (0·1-24·9). Geometric mean concentrations decreased by day 180 to 25·5 μg/mL (95% CI 20·6-31·5) in the high-dose group, 22·1 μg/mL (19·3-28·6) in the low-dose group, and 3·2 μg/mL (2·4-4·9) in the placebo group. 28 (57%) participants given high-dose vaccine and 31 (61%) participants given low-dose vaccine developed glycoprotein-specific CD4 cell responses, and 33 (67%) and 35 (69%), respectively, developed CD8 responses. INTERPRETATION: ChAd3-EBO-Z was safe and well tolerated, although mild to moderate systemic adverse events were common. A single dose was immunogenic in almost all vaccine recipients. Antibody responses were still significantly present at 6 months. There was no significant difference between doses for safety and immunogenicity outcomes. This acceptable safety profile provides a reliable basis to proceed with phase 2 and phase 3 efficacy trials in Africa. FUNDING: Swiss State Secretariat for Education, Research and Innovation (SERI), through the EU Horizon 2020 Research and Innovation Programme.

New England idyls, Op. 62

Soitinnus: Piano.

In Matth. XXVII:62 sqq. et XXVIII:4, 11-15

Errata.

Determinação de carbamato de etila em aguardentes de cana por CG-EM

A simple, specific and sensitive GC-MS procedure with ion m/z 62 was validated for the determination of ethyl carbamate (EC) in spirits. It exhibited linearity over the concentration of 30 to 600 μg/L with 30 μg/L limit of quantification. EC was detected in 70 of the 71 samples analyzed with levels from 33 to 2609 μg/L (mean level = 893 μg/L). 35% of the samples contained 500 to 1000 μg/L and 23% contained 150 to 500 and 1000 to 1500 μg/L. No significant correlation was found between EC and the levels of copper, pH and alcohol content of the samples.

Quantitative determination of acetaminophen, phenylephrine and carbinoxamine in tablets by high-performance liquid chromatography

An alternative methodology for analysis of acetaminophen (Ace), phenylephrine (Phe) and carbinoxamine (Car) in tablets by ion-pair reversed phase high performance liquid chromatography was validated. The pharmaceutical preparations were analyzed by using a C18 column (5 μm, 300 mm, 3.9 mm) and mobile phase consisting of 60% methanol and 40% potassium monobasic phosphate aqueous solution (62.46 mmol L-1) added with 1 mL phosphoric acid, 0.50 mL triethylamine and 0.25 g sodium lauryl sulfate. Isocratic analysis was performed under direct UV detection at 220 nm for Phe and Car and at 300 nm for Ace within 5 min.

Aplicação da cromatografia gasosa bidimensional abrangente com microdetector de captura de elétrons para determinação de agrotóxicos em sedimentos

Analysis of seven pesticides in sediments was successfully achieved using comprehensive two-dimensional gas chromatography with micro-electron capture detection, as it provided higher sensitivity and less matrix interference. Repeatability and intermediate precision of peak areas and heights were less than 4% and the recovery percentage for the analytes ranged from 52 to 115%. Instrumental LOD and LOQ were in the range of 0.60 to 2.31 μg L-1 and 1.83 to 5.62 μg L-1, respectively. Concentrations of 3.34 μg kg-1 (dry basis) for trifloxystrobin and azoxystrobin (below the LOQ) were found in a sediment sample.

62 gold 60 silver 63 bronze

kuv., 10 x 13 cm

62 médailles d'or 60 d'argent 63 de bronze

kuv., 10 x 13 cm

62 gold 60 silber 63 bronze

kuv., 10 x 13 cm

62 medallas de oro 60 ídem de plata 63 ídem de bronce

kuv., 10 x 13 cm

62 guld 60 silver 63 brons

kuv., 10 x 13 cm

Helsingissä kesällä 1921 Yhteissuomalaisen koulukokouksen 20-22/6, Kansanvalistusseuran laulujuhlien 23-26/6, Voimistelujuhlien 26-28/6 ja Messujen 28/6—2 /7 ohjelmat, sekä Helsingin Opas

kuv., 12 x 22 cm

Chrysler 62

kuv., 15 x 21 cm

Hepatite infecciosa canina: 62 casos

Os protocolos de necropsias realizadas em 5.361 cães durante um período de 43 anos (1964-2006) foram revisados em busca de casos de hepatite infecciosa canina (HIC) e sessenta e dois (1,2%) casos foram encontrados. A maioria dos 62 cães afetados tinha dois anos de idade ou menos (91,9%). Os sinais clínicos foram anotados nos protocolos de necropsia de 45 cães afetados por HIC e incluíam anorexia (55,6%), apatia (35,6%), diarréia (35,6%), freqüentemente com sangue (43,8% dos casos de diarréia), distúrbios neurológicos (33,3%), vômito (26,7%), petéquias e equimoses nas membranas mucosas e/ou pele (24,4%), hipotermia (20,0%), dor abdominal (15,6%), icterícia (13,3%), aumento de volume e congestão das tonsilas (11,1%), febre (11,1%) e ascite (6,7%). A duração do curso clínico variou de poucas horas a 15 dias. Os principais achados de necropsia incluíram alterações hepáticas (87,1%), linfonodos edematosos, congestos e hemorrágicos (51,6%), líquido sanguinolento, líquido claro ou sangue na cavidade abdominal (35,5%), víbices, sufusões e petéquias sobre a pleura visceral (27,4%) e superfície serosa das vísceras gastrintestinais (24,2%). Em 12,9% dos casos a serosa do intestino tinha aspecto granular. Hemorragias cerebrais nas leptomeninges e na substância do encéfalo foram observadas em 9,7% dos casos. As alterações hepáticas macroscópicas incluíam fígados moderadamente aumentados de volume, mais friáveis, com acentuação do padrão lobular, congestos e com múltiplos focos de necrose pálidos ou hemorrágicos. Películas e filamentos de fibrina cobriam a superfície hepática em 20,4% dos casos e em 27,8% dos casos a parede da vesícula biliar estava espessada por edema. Necrose hepática zonal ou aleatória (93,5% dos casos) associada a corpúsculos de inclusão intranucleares foi a lesão histológica mais regularmente encontrada. Os corpúsculos de inclusão intranucleares ocorreram no fígado em todos os casos e esse foi o critério para confirmação do diagnóstico. As lesões histológicas extra-hepáticas mais importantes incluíram hemorragias e corpúsculos de inclusão em células endoteliais do tufo glomerular renal (50,0%) dos linfonodos (47,8%) , do encéfalo (27,8%), das tonsilas (25,0%) e do baço (10,0%).