Safety of human immunisation with a live-attenuated Mycobacterium tuberculosis vaccine: a randomised, double-blind, controlled phase I trial.

BACKGROUND: Tuberculosis remains one of the world's deadliest transmissible diseases despite widespread use of the BCG vaccine. MTBVAC is a new live tuberculosis vaccine based on genetically attenuated Mycobacterium tuberculosis that expresses most antigens present in human isolates of M tuberculosis. We aimed to compare the safety of MTBVAC with BCG in healthy adult volunteers. METHODS: We did this single-centre, randomised, double-blind, controlled phase 1 study at the Centre Hospitalier Universitaire Vaudois (CHUV; Lausanne, Switzerland). Volunteers were eligible for inclusion if they were aged 18-45 years, clinically healthy, HIV-negative and tuberculosis-negative, and had no history of active tuberculosis, chemoprophylaxis for tuberculosis, or BCG vaccination. Volunteers fulfilling the inclusion criteria were randomly assigned to three cohorts in a dose-escalation manner. Randomisation was done centrally by the CHUV Pharmacy and treatments were masked from the study team and volunteers. As participants were recruited within each cohort, they were randomly assigned 3:1 to receive MTBVAC or BCG. Of the participants allocated MTBVAC, those in the first cohort received 5 × 10(3) colony forming units (CFU) MTBVAC, those in the second cohort received 5 × 10(4) CFU MTBVAC, and those in the third cohort received 5 × 10(5) CFU MTBVAC. In all cohorts, participants assigned to receive BCG were given 5 × 10(5) CFU BCG. Each participant received a single intradermal injection of their assigned vaccine in 0·1 mL sterile water in their non-dominant arm. The primary outcome was safety in all vaccinated participants. Secondary outcomes included whole blood cell-mediated immune response to live MTBVAC and BCG, and interferon γ release assays (IGRA) of peripheral blood mononuclear cells. This trial is registered with ClinicalTrials.gov, number NCT02013245. FINDINGS: Between Jan 23, 2013, and Nov 6, 2013, we enrolled 36 volunteers into three cohorts, each of which consisted of nine participants who received MTBVAC and three who received BCG. 34 volunteers completed the trial. The safety of vaccination with MTBVAC at all doses was similar to that of BCG, and vaccination did not induce any serious adverse events. All individuals were IGRA negative at the end of follow-up (day 210). After whole blood stimulation with live MTBVAC or BCG, MTBVAC was at least as immunogenic as BCG. At the same dose as BCG (5×10(5) CFU), although no statistical significance could be achieved, there were more responders in the MTBVAC group than in the BCG group, with a greater frequency of polyfunctional CD4+ central memory T cells. INTERPRETATION: To our knowledge, MTBVAC is the first live-attenuated M tuberculosis vaccine to reach clinical assessment, showing similar safety to BCG. MTBVAC seemed to be at least as immunogenic as BCG, but the study was not powered to investigate this outcome. Further plans to use more immunogenicity endpoints in a larger number of volunteers (adults and adolescents) are underway, with the aim to thoroughly characterise and potentially distinguish immunogenicity between MTBVAC and BCG in tuberculosis-endemic countries. Combined with an excellent safety profile, these data support advanced clinical development in high-burden tuberculosis endemic countries. FUNDING: Biofabri and Bill & Melinda Gates Foundation through the TuBerculosis Vaccine Initiative (TBVI).

TransPromo communication as a part of company’s marketing communications when the e-bill is a medium

The goal of this thesis was to research what TransPromo is, why companies want to implement TransPromo communication, and what the elements of effective Transpromo communication are. Furthermore, the goal was to develop a TransPromo communication strategy and a normative model for TeliaSonera Finland, which depicts the elements of effective TransPromo communication when the electronic bill is a medium. Abductive reasoning was utilized in this thesis, which means that empirical and theoretical worlds are alternating in researcher’s reasoning process. This thesis didn’t rely on any specific theory nor did it utilize any previous theoretical model. However, certain theoretical connections existed so this thesis cannot be considered purely inductive. The empirical part of this thesis was conducted by examining secondary industry data and by conducting specialist interviews at TeliaSonera Finland and Strålfors. Grounded Theory approach was utilized in the analysis of the interview data and content analysis was used in the analysis of secondary industry data. This thesis increases knowledge in the area of TransPromo communication, and provides one definition of TransPromo communication. As a result of this thesis, a TransPromo communication strategy and a normative model for TeliaSonera Finland was built. The model depicts the elements of the effective TransPromo communication when the e-bill is a medium. The TranPromo communication objective is to utilize transaction documents, such as bills, in order to deliver targeted and personalized marketing messages to current customers. The aim is to strengthen the customer relationship, and to enforce up-sell and cross-sell opportunities and cost savings.

Determination of cocaine in brazilian paper currency by capillary gas chromatography/mass spectrometry

The presence of illicit drugs such as cocaine and marijuana in US paper currency is very well demonstrated. However, there is no published study describing the presence of cocaine and/or other illicit drugs in Brazilian paper currency. In this study, Brazilian banknotes were collected from nine cities, extracted and analyzed by capillary gas chromatography/mass spectrometry, in order to investigate the presence of cocaine. Bills were extracted with deionized water followed by ethyl acetate. Results showed that 93% of the bills presented cocaine in a concentration range of 2.38-275.10 µg/bill.

Martin Bucer : Schriften zu Kirchengütern und Briefe

Kirjallisuusarvostelu

O ens realissimum e a existência: notas sobre o conceito de impessoalidade em Ser e Tempo, de Martin Heidegger

Neste artigo examinamos a noção de impessoalidade (das Man), apresentada em Ser e Tempo, de Martin Heidegger. Tomando como via interpretativa a análise de uma comparação estabelecida por Heidegger entre o das Man e o conceito de ens realissimum, sustenta-se que a impessoalidade possui uma função ontológica central no programa da ontologia fundamental. O modo de ser impessoal representa a fonte elementar de toda inteligibilidade, de modo análogo ao modo como o conceito de ens realissimum, na tradição ontoteológica, significou o fundamento de determinação de coisas em geral. Assim, o paralelo entre as noções de impessoalidade e ens realissimum permite captar a natureza social da projeção de ser pela compreensão de ser que caracteriza o ser humano.

Bill Maher naurattaa, muttei vakuuta

Elokuva-arvostelu

Totuuden kakkua viipaloimassa : vastaus Martin Kuschille

Nimekkeen selitys: Vastaus artikkeliin Koko totuus totuudesta, Tiede & edistys -lehdessä 4/91.

Att möta den andra : det pedagogiska uppdraget i ljuset av Martin Bubers dialogfilosofi

Vad innebär det att vara lärare? Vad handlar det pedagogiska uppdraget om? Vad behöver människan för att leva? I en tid präglad av internationella kunskapsmätningar och ekonomiska krav på lönsamhet och effektivitet ligger det nära till hands att lärarens uppgift begränsas till det som är mätbart, som ger snabba resultat och som svarar mot den globala marknadens krav. Det pedagogiska uppdraget handlar dock om mera än detta och beskrivs i lärarprofessionslitteratur som ett dubbelt uppdrag. För att leva behöver människan kunskap, men hon behöver också (lära sig att leva som) en medmänniska. Det innefattar dels uppdraget att främja och utveckla kunskaper, färdigheter och attityder hos eleven, men inkluderar också ett moraliskt ansvarsperspektiv för läraren att i undervisningssituationerna leva som en närvarande medmänniska tillsammans med eleven. Den lärare som ”enbart undervisar” fullgör inte sitt pedagogiska uppdrag, men det gör heller inte den som struntar i att utveckla elevens kunskaper och enbart är en ”trevlig medmänniska”. Pedagogikens dubbla uppdrag analyseras och utvecklas i avhandlingen utgående från Martin Bubers dialogfilosofi, som formulerar människans dubbla hållning till omvärlden: som Jag till Det och Jag med Du. I den pedagogiska verksamheten ligger fokus naturligt på kunskapandet (Jag-Det), varför påminnelsen om medlevandet (Jag-Du) är relevant. I Jag-Du-möten öppnas möjligheter för lärare och elever att erfara det annorlunda, det oväntade, det som avviker från det redan kategoriserade, det som erbjuder nya perspektiv. I den meningen bidrar Jag-Du-möten till kunskapsutvecklingen genom insikter och lärande av oförutsett slag. Samtidigt är det i dessa medlevande möten som elevens (och också lärarens) medvetenhet om vad det är att människa tillsammans med andra människor växer.