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.

Knapsack sets for cryptography

The basic goal of this study is to extend old and propose new ways to generate knapsack sets suitable for use in public key cryptography. The knapsack problem and its cryptographic use are reviewed in the introductory chapter. Terminology is based on common cryptographic vocabulary. For example, solving the knapsack problem (which is here a subset sum problem) is termed decipherment. Chapter 1 also reviews the most famous knapsack cryptosystem, the Merkle Hellman system. It is based on a superincreasing knapsack and uses modular multiplication as a trapdoor transformation. The insecurity caused by these two properties exemplifies the two general categories of attacks against knapsack systems. These categories provide the motivation for Chapters 2 and 4. Chapter 2 discusses the density of a knapsack and the dangers of having a low density. Chapter 3 interrupts for a while the more abstract treatment by showing examples of small injective knapsacks and extrapolating conjectures on some characteristics of knapsacks of larger size, especially their density and number. The most common trapdoor technique, modular multiplication, is likely to cause insecurity, but as argued in Chapter 4, it is difficult to find any other simple trapdoor techniques. This discussion also provides a basis for the introduction of various categories of non injectivity in Chapter 5. Besides general ideas of non injectivity of knapsack systems, Chapter 5 introduces and evaluates several ways to construct such systems, most notably the "exceptional blocks" in superincreasing knapsacks and the usage of "too small" a modulus in the modular multiplication as a trapdoor technique. The author believes that non injectivity is the most promising direction for development of knapsack cryptosystema. Chapter 6 modifies two well known knapsack schemes, the Merkle Hellman multiplicative trapdoor knapsack and the Graham Shamir knapsack. The main interest is in aspects other than non injectivity, although that is also exploited. In the end of the chapter, constructions proposed by Desmedt et. al. are presented to serve as a comparison for the developments of the subsequent three chapters. Chapter 7 provides a general framework for the iterative construction of injective knapsacks from smaller knapsacks, together with a simple example, the "three elements" system. In Chapters 8 and 9 the general framework is put into practice in two different ways. Modularly injective small knapsacks are used in Chapter 9 to construct a large knapsack, which is called the congruential knapsack. The addends of a subset sum can be found by decrementing the sum iteratively by using each of the small knapsacks and their moduli in turn. The construction is also generalized to the non injective case, which can lead to especially good results in the density, without complicating the deciphering process too much. Chapter 9 presents three related ways to realize the general framework of Chapter 7. The main idea is to join iteratively small knapsacks, each element of which would satisfy the superincreasing condition. As a whole, none of these systems need become superincreasing, though the development of density is not better than that. The new knapsack systems are injective but they can be deciphered with the same searching method as the non injective knapsacks with the "exceptional blocks" in Chapter 5. The final Chapter 10 first reviews the Chor Rivest knapsack system, which has withstood all cryptanalytic attacks. A couple of modifications to the use of this system are presented in order to further increase the security or make the construction easier. The latter goal is attempted by reducing the size of the Chor Rivest knapsack embedded in the modified system. '

Hume e o argumento do desígnio

Neste artigo pretendo apresentar a crítica de Hume ao argumento do desígnio bem como algumas interpretações acerca desta crítica, a partir de João Paulo Monteiro, Graham Oppy, Daniel Dennett e Richard Dawkins.

Resistência de cultivares de alfafa à antracnose e à mancha de leptosphaerulina em Uberlândia-MG

Tendo em vista a importância da alfafa como forrageira para a produção de feno de alta qualidade, avaliou-se a susceptibilidade de 27 cultivares às doenças de parte aérea bem como progresso da doença nas condições climáticas da região de Uberlândia-MG. As doenças diagnosticadas foram: antracnose (Colletotrichum trifolii Bain & Essary) e mancha de leptosferulina (Leptosphaerulina briosiana (Pollaci) J. H. Graham & Luttrel). Os resultados indicaram as cultivares BR1, MONARCA, SUTTER, MARICOPA, BR4, SW821O, 5929 e MH15 mais resistentes às lesões de leptosferulina. As cultivares ARAUCANA, IC1990, MH15 E SW8112A mostraram-se resistentes à antracnose. As cultivares Maricopa e ICI990 não apresentaram desfolha. O trabalho apresentou uma correlação simples significativa entre severidade da antracnose e porcentagem de desfolha. O modelo quadrático adequou-se para a curva de progresso da doença da mancha de leptosferulina.

Prevalência de sintomas do climatério em mulheres dos meios rural e urbano no Rio Grande do Norte, Brasil

OBJETIVO: avaliar a sintomatologia climatérica e fatores relacionados entre mulheres dos meios urbano e rural do Rio Grande do Norte. MÉTODOS: estudo transversal, descritivo, envolvendo casuística de 261 mulheres climatéricas residentes em Natal e Mossoró (grupo urbano; n=130) e Uruaçu, em São Gonçalo do Amarante (grupo rural; n=131). A sintomatologia climatérica foi avaliada pelo Índice Menopausal de Blatt-Kupperman (IMBK) e Escala Climatérica de Greene (ECG). A análise estatística constou de comparações das medianas dos escores entre os grupos e regressão logística. Definiram-se como "muito sintomáticas" as pacientes com escores >20, para ambos instrumentos (variável dependente). As variáveis independentes foram: idade, procedência, alfabetização, obesidade e prática de atividade física. RESULTADOS: o grupo urbano apresentou escores significativamente superiores ao grupo rural, tanto para o IMBK (medianas de 26,0 e 17,0, respectivamente; p<0,0001), quanto para a ECG (medianas de 27,0 e 16,0, respectivamente; p<0,0001). Na amostra total, evidenciou-se que 56,3% (n=147) das mulheres foram classificadas como "muito sintomáticas". Na comparação intergrupos, essa prevalência foi significativamente mais elevada nas mulheres urbanas em relação às rurais (79,2 e 33,6%, respectivamente; p<0,05). Pela análise de regressão logística, evidenciou-se que a chance de pertencer ao grupo definido como "muito sintomáticas" foi maior para mulheres do meio urbano [odds ratio ajustado (OR)=7,1; 95% intervalo de confiança a 95% (IC95%)=3,69-13,66] e alfabetizadas (OR=2,19; IC95%=1,16-4,13). A idade superior a 60 anos associou-se com menor chance de ocorrência de sintomas significativos (OR=0,38; IC95%=0,17-0,87). CONCLUSÕES: a prevalência de sintomas climatéricos significativos é menor em mulheres do meio rural, demonstrando que fatores socioculturais e ambientais estão fortemente relacionados ao surgimento dos sintomas climatéricos em nossa população.

Voitelukirja

33 x 20 cm

Yksityiskohdat malleista 612, 615, 621, 827, 837

kuv., 13 x 21 cm

Specifikationer över modellerna 612, 615, 621, 827, 837

kuv., 13 x 21 cm

Olennaisinta ornitologiaa

Kirjallisuusarvostelu

Maantieteen opetuksesta kaikilta kanteilta

Kirjallisuusarvostelu

Spekulaation materiaalinen paluu ja välttämätön kontingenssi

Kirjallisuusarvostelu

Acanthaceae da Reserva Florestal Mata do Paraíso, Viçosa, Minas Gerais

O trabalho apresenta o levantamento das Acanthaceae da Reserva Florestal Mata do Paraíso, no Município de Viçosa, MG, uma área predominantemente florestal do complexo vegetacional da Mata Atlântica. Foram registrados quatro gêneros e seis espécies: Geissomeria schottiana Nees, Justicia scheidweileri V.A.W. Graham, Mendoncia velloziana Mart., Ruellia brevifolia (Pohl) C. Ezcurra, R. menthoides (Nees) Hiern e R. subsessilis (Nees) Lindau, sendo que R. menthoides constituiu uma nova citação para Minas Gerais. São apresentadas chaves analíticas para gêneros e espécies, descrições, ilustrações, comentários taxonômicos e informações sobre usos e distribuição geográfica das espécies.

Tunnuslukuperusteisten sijoitusstrategioiden menestys Suomen osakemarkkinoilla finanssikriisin aikana

Tämän tutkielman tavoitteena on selvittää ja analysoida tunnuslukuihin perustuvien sijoitusstrategioiden tuottoja voimakkailla lasku- ja nousumarkkinoilla finanssikriisin aikana. Säilyttääkö arvostrategian alhaisten tunnuslukujen portfolio arvonsa laskukausilla parhaiten tai tuottaako kasvustrategia vahvalla nousukaudella parhaan tuoton? Miten yhtiöiden taloudellinen asema vaikuttaa tuottoihin jyrkillä laskukausilla ja nousukaudella? Tutkimusaineistona ovat julkisesti noteeratut Helsingin pörssin yhtiöt aikavälillä 13.7.2007 - 4.10.2011. Ajanjaksoon mahtuu kaksi laskukautta ja nousukausi. Yhtiöt on jaettu tunnuslukujen arvostuksen mukaan viiteen portfolioon. Tutkittavat tunnusluvut ovat P/E-luku, P/B-luku, EV/Ebit-luku, oman pääoman tuotto, omavaraisuusaste, current ratio ja Grahamin luku. Tulosten perusteella arvostrategia menestyi hyvin nousukaudella niin P/E-luvun kuin P/B-luvun kategorian tuotoissa, mutta ei erottunut edukseen laskukausilla. Huomattavaa oli myös korkean omavaraisuuden yhtiöiden voimakas defensiivisyys molemmilla laskukausilla. Toisaalta ne olivat myös nousukaudella vähätuottoisia.

Performance of value and momentum strategies in the Swedish stock market

This thesis investigates the performance of value and momentum strategies in the Swedish stock market during the 2000-2015 sample period. In addition the performance of some value and value-momentum combination is examined. The data consists of all the publicly traded companies in the Swedish stock market between 2000-2015. P/E, P/B, P/S, EV/EBITDA, EV/S ratios and 3, 6 and 12 months value criteria are used in the portfolio formation. In addition to single selection criteria, combination of P/E and P/B (aka. Graham number), the average ranking of the five value criteria and EV/EBIT – 3 month momentum combination is used as a portfolio-formation criterion. The stocks are divided into quintile portfolios based on each selection criterion. The portfolios are reformed once a year using the April’s price information and previous year’s financial information. The performance of the portfolios is examined based on average annual return, the Sharpe ratio and the Jensen alpha. The results show that the value-momentum combination is the best-performing portfolio both during the whole sample period and during the sub-period that started after the 2007-financial crisis.