Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial

Background A vaccine against HIV is widely considered the most effective and sustainable way of reducing new infections. We evaluated the safety and impact of boosting with subtype C CN54rgp140 envelope protein adjuvanted in glucopyranosyl lipid adjuvant (GLA-AF) in Tanzanian volunteers previously given three immunizations with HIV-DNA followed by two immunizations with recombinant modified vaccinia virus Ankara (HIV-MVA). Methods Forty volunteers (35 vaccinees and five placebo recipients) were given two CN54rgp140/GLA-AF immunizations 30-71 weeks after the last HIV-MVA vaccination. These immunizations were delivered intramuscularly four weeks apart. Results The vaccine was safe and well tolerated except for one episode of asymptomatic hypoglycaemia that was classified as severe adverse event. Two weeks after the second HIV-MVA vaccination 34 (97%) of the 35 previously vaccinated developed Env-specific binding antibodies, and 79% and 84% displayed IFN-gamma ELISpot responses to Gag and Env, respectively. Binding antibodies to subtype C Env (included in HIV-DNA and protein boost), subtype B Env (included only in HIV-DNA) and CRF01_AE Env (included only in HIV-MVA) were significantly boosted by the CN54rgp140/GLA-AF immunizations. Functional antibodies detected using an infectious molecular clone virus/peripheral blood mononuclear cell neutralization assay, a pseudovirus/TZM-bl neutralization assay or by assays for antibody-dependent cellular cytotoxicity (ADCC) were not significantly boosted. In contrast, T-cell proliferative responses to subtype B MN antigen and IFN-gamma ELISpot responses to Env peptides were significantly enhanced. Four volunteers not primed with HIV-DNA and HIV-MVA before the CN54rgp140/ GLA-AF immunizations mounted an antibody response, while cell-mediated responses were rare. After the two Env subtype C protein immunizations, a trend towards higher median subtype C Env binding antibody titers was found in vaccinees who had received HIV-DNA and HIV-MVA prior to the two Env protein immunizations as compared to unprimed vaccinees (p = 0.07). Conclusion We report excellent tolerability, enhanced binding antibody responses and Env-specific cell-mediated immune responses but no ADCC antibody increase after two immunizations with a subtype C rgp140 protein adjuvanted in GLA-AF in healthy volunteers previously immunized with HIV-DNA and HIV-MVA

Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design

Background We evaluated the safety and immunogenicity of (i) an intradermal HIV-DNA regimen given with/without intradermal electroporation (EP) as prime and (ii) the impact of boosting with modified vaccinia virus Ankara (HIV-MVA) administered with or without subtype C CN54rgp140 envelope protein adjuvanted with Glucopyranosyl Lipid A (GLA-AF) in volunteers from Tanzania and Mozambique. Methods Healthy HIV-uninfected adults (N = 191) were randomized twice;first to one of three HIV-DNA intradermal priming regimens by needle-free ZetaJet device at weeks 0, 4 and 12 (Group I: 2x0.1mL [3mg/mL], Group II: 2x0.1mL [3mg/mL] plus EP, Group III: 1x0.1mL 6mg/mL] plus EP). Second the same volunteers received 10(8) pfu HIV-MVA twice, alone or combined with CN54rgp140/GLA-AF, intramuscularly by syringe, 16 weeks apart. Additionally, 20 volunteers received saline placebo. Results Vaccinations and electroporation did not raise safety concerns. After the last vaccination, the overall IFN-gamma ELISpot response rate to either Gag or Env was 97%. Intradermal electroporation significantly increased ELISpot response rates to HIV-DNA-specific Gag (66% group I vs. 86% group II, p = 0.026), but not to the HIV-MVA vaccine-specific Gag or Env peptide pools nor the magnitude of responses. Co-administration of rgp140/GLA-AF with HIV-MVA did not impact the frequency of binding antibody responses against subtype B gp160, C gp140 or E gp120 antigens (95%, 99%, 79%, respectively), but significantly enhanced the magnitude against subtype B gp160 (2700 versus 300, p<0.001) and subtype C gp140 (24300 versus 2700, p<0.001) Env protein. At relatively low titers, neutralizing antibody responses using the TZM-bl assay were more frequent in vaccinees given adjuvanted protein boost. Conclusion Intradermal electroporation increased DNA-induced Gag response rates but did not show an impact on Env-specific responses nor on the magnitude of responses. Co-administration of HIV-MVA with rgp140/GLA-AF significantly enhanced antibody responses

Multifaceted Communication Problems in Everyday Conversations Involving People with Parkinson’s Disease

It is known that Parkinson’s disease is often accompanied by a motor speech disorder, which results in impaired communication. However, people with Parkinson’s disease may also have impaired word retrieval (anomia) and other communicative problems, which have a negative impact on their ability to participate in conversations with family as well as healthcare staff. The aim of the present study was to explore effects of impaired speech and language on communication and how this is managed by people with Parkinson’s disease and their spouses. Using a qualitative method based on Conversation Analysis, in-depth analyses were performed on natural conversational interaction in five dyads including elderly men who were at different stages of Parkinson’s disease. The findings showed that the motor speech disorder in combination with word retrieval difficulties and adaptations, such as using communication strategies, may result in atypical utterances that are difficult for communication partners to understand. The coexistence of several communication problems compounds the difficulties faced in conversations and individuals with Parkinson’s disease are often dependent on cooperation with their communication partner to make themselves understood

De möjliga effekterna av den blåa ekonomin på jämlikheten mellan könen i Republiken Seychellerna

In order to ensure the Earth’s future prosperity and welfare gender inequalities need to be tackled and our marine environment needs to be safeguarded. In this thesis we therefore evaluate the possible effects of a blue economy on gender equality in the Republic of Seychelles. Using a qualitative methodology, we have conducted 21 semi-structured interviews with a total of 35 respondents. These including people working at grassroots level, in non-governmental organisations and within the governmental bodies in Seychelles. In order to assist the collection and analysis of the data, we developed a theoretical model portraying in what ways the blue economy can affect gender equality in the country via three main components; maritime sustainability, technological innovation and new market and job opportunities. The empirical results demonstrate that the blue economy framework through these three components can affect gender equality, both in the short and long-term. If proven to be inclusive and implemented in the correct way, our findings portray that the blue economy will offer many opportunities. This affecting gender equality in diverse ways, with our main results showing that the concept will (i) help single mothers through factors such as increasing food security, water quality and new job opportunities; (ii) encouraging women to enter into more technological and/or male dominated fields; (iii) motivating boys to remain in school or help dropouts to venture into more practical fields.För att säkerställa jordens framtida välstånd och välfärd måste ojämlikheter mellan könen åtgärdas och vår marina miljö skyddas. I denna uppsats så utvärderar vi därför de möjliga effekterna av en blå ekonomi på jämlikheten mellan könen i Republiken Seychellerna. Via ett kvalitativt tillvägagångssätt genomförde vi 21 semistrukturerade intervjuer med 35 respondenter. Dessa inkluderade individer som arbetar på gräsrotsnivå, i icke-statliga organisationer och inom de statliga organen i Seychellerna. För att förenkla insamlingen och analysen av data utvecklade vi en teoretisk modell som visar på vilka sätt en blå ekonomi kan påverka jämlikheten mellan män och kvinnor i landet via tre huvudkomponenter; marin hållbarhet, teknologisk utveckling och nya marknads- och arbetsmöjligheter. De empiriska resultaten visar på att en blå ekonomi kan, genom dessa tre komponenter, påverka jämlikheten mellan män och kvinnor på både kort och lång sikt. Om konceptet implementeras på rätt sätt samt inkluderar hela befolkningen, tyder våra resultat på att en blå ekonomi kommer erbjuda många möjligheter och påverka jämlikheten mellan könen på olika sätt. Våra huvudsakliga resultat visar att konceptet kan (i) hjälpa ensamstående mödrar genom att öka livsmedelsförsörjningen, kvaliteten på vatten och erbjuda nya arbetsmöjligheter; (ii) uppmuntra kvinnor att gå in i mer tekniska och/eller mansdominerade yrken; (iii) motivera pojkar att stanna kvar i skolan eller hjälpa de utsatta att hitta arbete i mer praktiska områden

De möjliga effekterna av den blåa ekonomin på jämlikheten mellan könen i Republiken Seychellerna

In order to ensure the Earth’s future prosperity and welfare gender inequalities need to be tackled and our marine environment needs to be safeguarded. In this thesis we therefore evaluate the possible effects of a blue economy on gender equality in the Republic of Seychelles. Using a qualitative methodology, we have conducted 21 semi-structured interviews with a total of 35 respondents. These including people working at grassroots level, in non-governmental organisations and within the governmental bodies in Seychelles. In order to assist the collection and analysis of the data, we developed a theoretical model portraying in what ways the blue economy can affect gender equality in the country via three main components; maritime sustainability, technological innovation and new market and job opportunities. The empirical results demonstrate that the blue economy framework through these three components can affect gender equality, both in the short and long-term. If proven to be inclusive and implemented in the correct way, our findings portray that the blue economy will offer many opportunities. This affecting gender equality in diverse ways, with our main results showing that the concept will (i) help single mothers through factors such as increasing food security, water quality and new job opportunities; (ii) encouraging women to enter into more technological and/or male dominated fields; (iii) motivating boys to remain in school or help dropouts to venture into more practical fields.För att säkerställa jordens framtida välstånd och välfärd måste ojämlikheter mellan könen åtgärdas och vår marina miljö skyddas. I denna uppsats så utvärderar vi därför de möjliga effekterna av en blå ekonomi på jämlikheten mellan könen i Republiken Seychellerna. Via ett kvalitativt tillvägagångssätt genomförde vi 21 semistrukturerade intervjuer med 35 respondenter. Dessa inkluderade individer som arbetar på gräsrotsnivå, i icke-statliga organisationer och inom de statliga organen i Seychellerna. För att förenkla insamlingen och analysen av data utvecklade vi en teoretisk modell som visar på vilka sätt en blå ekonomi kan påverka jämlikheten mellan män och kvinnor i landet via tre huvudkomponenter; marin hållbarhet, teknologisk utveckling och nya marknads- och arbetsmöjligheter. De empiriska resultaten visar på att en blå ekonomi kan, genom dessa tre komponenter, påverka jämlikheten mellan män och kvinnor på både kort och lång sikt. Om konceptet implementeras på rätt sätt samt inkluderar hela befolkningen, tyder våra resultat på att en blå ekonomi kommer erbjuda många möjligheter och påverka jämlikheten mellan könen på olika sätt. Våra huvudsakliga resultat visar att konceptet kan (i) hjälpa ensamstående mödrar genom att öka livsmedelsförsörjningen, kvaliteten på vatten och erbjuda nya arbetsmöjligheter; (ii) uppmuntra kvinnor att gå in i mer tekniska och/eller mansdominerade yrken; (iii) motivera pojkar att stanna kvar i skolan eller hjälpa de utsatta att hitta arbete i mer praktiska områden

How to catch the carrot - En studie om synen på motivation och belöningssystem

I merparten av litteraturen för vårt valda ämne diskuteras yttre belöningar i form av ekonomisk ersättning ingående medan inre belöningar i form av till exempel erkännande och ökat ansvar bara benämns i förbifarten när det gäller motivation av de anställda. Den uppsats vi tagit del av som behandlar belöningssystem och motivationen menar att detta bör ändras då de i sin rapport fick fram att anställda värderar inre belöningar högre än yttre och ger det som förslag till vidare forskning. Vi kommer i den här uppsatsen att ytterligare undersöka detta fenomen och se ifall vi kan finna några ytterligare eller nya samband som kan vara bidrag till framtida forskning. Vårt syfte med denna uppsats är att undersöka personalens syn på belöningssystem samt motivation. Vidare vill vi undersöka vilka delar i belöningssystemet, det vill säga de yttre respektive inre belöningar samt individuella respektive kollektiva belöningar som har störst betydelse för personalens motivation. Vi har genomfört en fallstudie på hotellkoncernen First Hotel och First Hotel Jörgen Kock i Malmö. I vår uppsats intervjuades fyra personer på olika positioner inom hotellkedjan. Vårt empiriska material har vi sedan ställt mot teorier som behandlar motivation och belöningssystem Slutsatser vi har kommit fram till är att belöningssystem som motivationsfaktor anses som positivt. Synen på inre motivationen betraktas ha störst betydelse medan ekonomiska incitament inte är av någon större betydelse för motivationen. Detta ställer vi oss dock kritiska till eftersom det kan anses som mindre respekterat att säga att pengar är det enda som driver motivation. Vi fann även en tvetydighet gällande synen på om belöningar bör ges kollektivt eller individuellt. Vi menar oss kunna säga att ett belöningssystem är situationsbundet och för att nå rätt effekt måste anpassas efter givna förutsättningar

KPIs as the interface between scheduling and control

The integration of scheduling and control has been discussed in the past. While constructing an integrated plant model that may still seem out of reach, scheduling and control systems are increasingly more intertwined. We argue that they are in fact already integrated and give the example of two key performance indicators (KPIs) that are defined in the recent international standard ISO 22400. The focus of this study is on KPIs that consider both planned times and actual times. An amino acid production plant is used in the study, and the production is described from both the scheduling and the control perspective. To illustrate the integration, a schedule is computed containing the planned production times. Resulting measurements from the control system are analyzed for their actual production times using a proposed procedure that detects the start and end time of batches. Using KPIs as the interface between scheduling and control can be used as a strategy for maximizing the plant performance. The study focuses on the process industry

The English School as a theory and a scholarly community

It is becoming customary to define the English School (ES) as a group of scholars participating in a common inquiry related to a few central concepts, notably that of international society. Although the roots of the ES are often attributed to the British Committee on the Theory of International Politics, it is now said to be more of an open society of impersonal ties rather than an exclusive community based on personal relations. But how true is that assertion? If the School is theoretically open to anyone, why are its members predominantly male, white and Western? In this piece, we discuss three obstacles that prevent the ES from becoming a more inclusive venture

A reassessment of the discrepancies in the annual variation of δD-H2O in the tropical lower stratosphere between the MIPAS and ACE-FTS satellite data sets

The annual variation of δD in the tropical lower stratosphere is a critical indicator for the relative importance of different processes contributing to the transport of water vapour through the cold tropical tropopause region into the stratosphere. Distinct observational discrepancies of the δD annual variation were visible in the works of Steinwagner et al. (2010) and Randel et al. (2012). Steinwagner et al. (2010) analysed MIPAS (Michelson Interferometer for Passive Atmospheric Sounding) observations retrieved with the IMK/IAA (Institut für Meteorologie und Klimaforschung in Karlsruhe, Germany, in collaboration with the Instituto de Astrofísica de Andalucía in Granada, Spain) processor, while Randel et al. (2012) focused on ACE-FTS (Atmospheric Chemistry Experiment Fourier Transform Spectrometer) observations. Here we reassess the discrepancies based on newer MIPAS (IMK/IAA) and ACE-FTS data sets, also showing for completeness results from SMR (Sub-Millimetre Radiometer) observations and a ECHAM/MESSy (European Centre for Medium-Range Weather Forecasts Hamburg and Modular Earth Submodel System) Atmospheric Chemistry (EMAC) simulation (Eichinger et al., 2015b). Similar to the old analyses, the MIPAS data set yields a pronounced annual variation (maximum about 75 ‰), while that derived from the ACE-FTS data set is rather weak (maximum about 25 ‰). While all data sets exhibit the phase progression typical for the tape recorder, the annual maximum in the ACE-FTS data set precedes that in the MIPAS data set by 2 to 3 months. We critically consider several possible reasons for the observed discrepancies, focusing primarily on the MIPAS data set. We show that the δD annual variation in the MIPAS data up to an altitude of 40 hPa is substantially impacted by a “start altitude effect”, i.e. dependency between the lowermost altitude where MIPAS retrievals are possible and retrieved data at higher altitudes. In itself this effect does not explain the differences with the ACE-FTS data. In addition, there is a mismatch in the vertical resolution of the MIPAS HDO and H2O data (being consistently better for HDO), which actually results in an artificial tape-recorder-like signal in δD. Considering these MIPAS characteristics largely removes any discrepancies between the MIPAS and ACE-FTS data sets and shows that the MIPAS data are consistent with a δD tape recorder signal with an amplitude of about 25 ‰ in the lowermost stratosphere