This article presents some results from a large monitoring campaign performed in 22 buildings around the world as part of International Energy Agency (IEA) Task 50 “Advanced lighting solutions for ...retrofitting buildings”. This article mainly addresses the work of Subtask D, which aims to demonstrate sound lighting retrofit solutions in a selection of representative, typical Case Studies. In order to evaluate the Case Studies, a monitoring protocol was developed to assess the overall lighting performance taking into consideration: 1) Energy use, 2) Retrofit costs, 3) Photometric assessment, and 4) User assessment. The monitoring was carried out from June 2014 to December 2015 in 22 non-residential buildings in ten countries. This article presents results from selected Case Studies, drawing conclusions regarding retrofit solutions as well as reflecting on methodological procedures for the measurements and data collection. Measured data as well as key conclusions from Subtask D will be summarized in an electronic web and portable sourcebook at the end of the IEA Task 50 (December 2015), which will be freely available through the Internet.
Previous studies with the malaria vaccine RTS,S/AS02
A in young children in a malaria endemic area of Mozambique have shown it to have a promising safety profile and to reduce the risk of
Plasmodium ...falciparum infection and disease.
In this study, we assessed the antibody responses to the
P. falciparum and hepatitis B components of the RTS,S/AS02
A vaccine over a 45
months surveillance period in a large phase IIb trial which included 2022 children aged 1–4
years at recruitment.
The RTS,S/AS02
A vaccine induced high anti-circumsporozoite antibody levels with at least 96% of children remaining seropositive during the entire follow-up period. IgG titers decayed over the first 6
months of follow-up to about 25% of the initial level, but still remained 30-fold higher until month 45 compared to controls. Children with higher levels of naturally acquired immunity at baseline, assessed by blood stage indirect fluorescent antibody test, had slightly higher anti-circumsporozoite levels, after adjusting for the effect of age.
The RTS,S/AS02
A vaccine also induced high levels of anti-hepatitis B surface antigen antibodies (seroprotection >97%).
RTS,S/AS02
A vaccine is immunogenic and induces long-lasting anti-circumsporozoite antibodies, persisting at least 42
months after immunization. These antibodies may play a role in protection against malaria.
The goal of the Malaria Vaccine Program at the Walter Reed Army Institute of Research (WRAIR) is to develop a licensed multi-antigen, multi-stage vaccine against
Plasmodium falciparum able to prevent ...all symptomatic manifestations of malaria by preventing parasitemia. A secondary goal is to limit disease in vaccinees that do develop malaria. Malaria prevention will be achieved by inducing humoral and cellular immunity against the pre-erythrocytic circumsporozoite protein (CSP) and the liver stage antigen-1 (LSA-1). The strategy to limit disease will target immune responses against one or more blood stage antigens, merozoite surface protein-1 (MSP-1) and apical merozoite antigen-1 (AMA-1). The induction of T- and B-cell memory to achieve a sustained vaccine response may additionally require immunization with an adenovirus vector such as adenovirus serotype 35. RTS,S, a CSP-derived antigen developed by GlaxoSmithKline Biologicals in collaboration with the Walter Reed Army Institute of Research over the past 17 years, is the cornerstone of our program. RTS,S formulated in AS02A (a GSK proprietary formulation) is the only vaccine candidate shown in field trials to prevent malaria and, in one instance, to limit disease severity. Our vaccine development plan requires proof of an individual antigen's efficacy in a Phase 2 laboratory challenge or field trial prior to its integration into an RTS,S-based, multi-antigen vaccine. Progress has been accelerated through extensive partnerships with industrial, academic, governmental, and non-governmental organizations. Recent safety, immunogenicity, and efficacy trials in the US and Africa are presented, as well as plans for the development of a multi-antigen vaccine.
Abstract Plasmodium falciparum Liver Stage Antigen 1 (LSA-1) is a pre-erythrocytic stage antigen. Our LSA-1 vaccine candidate is a recombinant protein with full-length C- and N-terminal flanking ...domains and two of the 17 amino acid repeats from the central repeat region termed “LSA-NRC.” We describe the first Phase I/II study of this recombinant LSA-NRC protein formulated with either the AS01 or AS02 adjuvant system. We conducted an open-label Phase I/II study. Thirty-six healthy malaria-naïve adults received one of four formulations by intra-deltoid injection on a 0 and 1 month schedule; low dose (LD) LSA-NRC/AS01:10 μg LSA-NRC/0.5 ml AS01 ( n = 5), high dose (HD) LSA-NRC/AS01: 50 μg LSA-NRC/0.5 ml AS01 ( n = 13); LD LSA-NRC/AS02: 10 μg LSA-NRC/0.5 ml AS02 ( n = 5) and HD LSA-NRC/AS02: 50 μg LSA-NRC/0.5 ml AS02 ( n = 13). Two weeks post-second immunization, the high dose vaccinees and 6 non-immunized infectivity controls underwent experimental malaria sporozoite challenge. The vaccines showed a reassuring safety profile but were moderately reactogenic. There were no serious adverse events. All subjects seroconverted after the first immunization. Following the second immunization, LSA-1-specific CD4+ T cells producing two cytokines (IL-2 and IFN-γ) were found by intra-cellular staining in all subjects in the LD LSA-NRC/AS01B group and in 3 of 5 subjects in the LD LSA-NRC/AS02 group. In contrast, the HD LSA-NRC/AS01 and HD LSA-NRC/AS02 group subjects had fewer LSA-1-specific CD4+ T cells, and minimal to no IFN-γ responses. There was no increase in LSA-1-specific CD8+ T cells found in any group. Per protocol, 22 high dose vaccinees, but no low dose vaccinees, underwent P. falciparum homologous malaria challenge (3D7 clone). All vaccinees became parasitemic and there was no delay in their pre-patent period versus controls ( p = 0.95). LSA-NRC/AS01 and LSA-NRC/AS02 elicited antigen-specific antibody and CD4+ T cell responses, but elicited no protective immunity. Although the optimal antigen dose of LSA-NRC may not have been selected for the challenge portion of the protocol, further vaccine development based upon LSA-1 should not be excluded and should include alternative vaccine platforms able to elicit additional effector mechanisms such as CD8+ T cells.
Background. The RTS,S/AS01E malaria candidate vaccine is being developed for immunization of African infants through the Expanded Program of Immunization (EPI). Methods. This phase 2, randomized, ...open, controlled trial conducted in Ghana, Tanzania, and Gabon evaluated the safety and immunogenicity of RTS,S/AS01E when coadministered with EPI vaccines. Five hundred eleven infants were randomized to receive RTS,S/AS01E at 0, 1, and 2 months (in 3 doses with diphtheria, tetanus, and wholecell pertussis conjugate DTPw; hepatitis B HepB; Haemophilus influenzae type b Hib; and oral polio vaccine OPV), RTS,S/AS01E at 0, 1, and 7 months (2 doses with DTPwHepB/Hib+OPV and 1 dose with measles and yellow fever), or EPI vaccines only. Results. The occurrences of serious adverse events were balanced across groups; none were vaccine-related. One child from the control group died. Mild to moderate fever and diaper dermatitis occurred more frequently in the RTS,S/AS01E coadministration groups. RTS,S/AS01E generated high anti-circumsporozoite protein and anti- hepatitis B surface antigen antibody levels. Regarding EPI vaccine responses upon coadministration when considering both immunization schedules, despite a tendency toward lower geometric mean titers to some EPI antigens, predefined noninferiority criteria were met for all EPI antigens except for polio 3 when EPI vaccines were given with RTS,S/AS01E at 0, 1, and 2 months. However, when antibody levels at screening were taken into account, the rates of response to polio 3 antigens were comparable between groups. Conclusion. RTS,S/AS01E integrated in the EPI showed a favorable safety and immunogenicity evaluation. Trial registration. ClinicalTrials.gov identifier: NCT00436007. GlaxoSmithKline study ID number: 106369 (Malaria-050).
This paper presents a holistic approach to perform energy renovations of office buildings. A real case study is used to demonstrate how different software can be used to facilitate the work of ...architects and engineers during different design stages. Initially, the moisture safety of the building is coupled to its energy performance to define the optimum insulation level. The new interior layout is based on an initial daylight study, rather than on architectural intuition. On a second stage, shading and natural ventilation are studied to eradicate any cooling demand, while the interdependence between heating energy and daylight is assessed for the use of light-wells. To demonstrate the trade-offs between visual control and electrical lighting, different shading systems are examined for a cellular office. Finally, two alternate HVAC systems are analyzed to investigate whether passive standards can be achieved with an all-air system and/or a hydronic system.
•Demonstration of daylight, moisture and HVAC design tools for energy renovations.•New plan layout design based on initial solar irradiation and daylight analyses.•Position of added insulation determined through a detailed moisture analysis.•Assessment of shading devices based on visual comfort and electric lighting use.•Design of an efficient HVAC system based on an all-air or a hydronic system.
L’histoire des tout débuts du christianisme pose à l’enquêteur de faits historiquement assurés des obstacles considérables. Les trous noirs y abondent et les ambiguïtés de sens engagent souvent sur ...de fausses pistes. Les textes de référence informative n’ont pas pour objectif premier l’objectivité historique. Leur transformation par les Églises chrétiennes en livres sacrés ne correspond pas non plus à leur objectif initial, interdisant ou gênant toute interrogation à leur sujet. Leur but, notamment dans les premiers documents écrits, était de montrer que l’enseignement de Jésus et sa vie étaient en conformité avec le contenu des livres saints du judaïsme, et que les innovations n’étaient pas des rejets, mais des adaptations inspirées par des manières plus intelligentes de compréhension de la Loi divine. Trois questions sont abordées. La première concerne des fragments méconnus ou discutés de la vie de Jésus, tels qu’ils sont rapportés par les Évangiles et interprétés par la tradition. On peut y apporter quelques éclaircissements au vu de la comparaison des textes et de ce qu’on peut connaître de la vie des Juifs en son temps. La deuxième porte sur l’origine et les objectifs du texte connu sous le nom d’« Apocalypse de saint Jean », texte énigmatique qui a eu du mal à être intégré aux textes canoniques du christianisme. On peut en comprendre les raisons et en revoir le contenu en fonction d’hypothèses nouvelles. La troisième entraîne une révision de l’histoire des persécutions des chrétiens, au cours des quatre premiers siècles de l’Empire romain païen, où la théologie appliquée à l’histoire et l’inspiration poétique ont détourné moins de la réalité historique que du sens donné par une tradition à la fois victimaire et triomphaliste. Il s’agit là de questions – présentées comme questions, et non comme réponses définitives – qui n’affectent en rien les choix religieux ou idéologiques des lecteurs. Elles importent à tous ceux qui éprouvent un intérêt pour la recherche d’un sens crédible, à défaut de vérité absolue, des faits d’histoire et pour l’influence (pas forcément maléfique) qu’exerce sur eux l’activité de l’imaginaire.
Previous trials of the RTS, S malaria candidate vaccine have shown that this vaccine is safe, tolerated and immunogenic. The development plan for this vaccine aims at administering it in the first ...year of life through the Expanded Program on Immunization (EPI). The objective was to evaluate the safety and reactogenicity of RTS, S/AS02D (0.5 ml dose), a pediatric formulation of GlaxoSmithKline Biologicals' current malaria candidate vaccine RTS, S/AS02A (0.25 ml dose). A 0.5 ml dose of AS02D is composed of the same active ingredients in the same quantities as in a 0.25 ml dose of AS02A and has been developed to be easily introduced into routine EPI practices.
We performed a phase I/IIb randomized double-blind bridging study in a malaria-endemic region of Mozambique, to compare the safety and immunogenicity of both candidate vaccines with the aim of replacing RTS, S/AS02A with RTS, S/AS02D as the candidate pediatric vaccine. 200 Mozambican children aged 3 to 5 years were randomized 1:1 to receive one of the 2 vaccines according to a 0, 1, 2 month schedule.
Both vaccines were safe and had similar reactogenicity profiles. All subjects with paired pre and post-vaccination samples showed a vaccine response with respect to anti-circumsporozoite (CS) antibodies irrespective of initial anti-CS serostatus. Geometric mean titers (GMTs) were 191 EU/ml (95% CI 150-242) in recipients of RTS, S/AS02D compared to 180 EU/ml (95% CI 146-221) in recipients of RTS, S/AS02A. For the anti-hepatitis B surface antigen (HBsAg), all subjects were seroprotected at day 90, and the GMTs were 23,978 mIU/ml (95% CI 17,896-32,127) in RTS, S/AS02D recipients and 17,410 mIU/ml (95% CI 13,322-22,752) in RTS, S/AS02A recipients. There was a decrease in anti-CS GMTs between months 3 and 14 in both groups (191 vs 22 EU/mL in RTS, S/AS02D group and 180 vs 29 EU/mL in RTS, S/AS02A group).
Our data show that the RTS, S/AS02D is safe, well tolerated, and demonstrates non-inferiority (defined as upper limit of the 95% confidence interval of the anti-CS GMT ratio of RTS, S/AS02A to RTS, S/AS02D below 3.0) of the antibody responses to circumsporozoite and HBsAg induced by the RTS, S/AS02D as compared to the RTS, S/AS02A.
Abstract We conducted an open-label safety and immunogenicity bridging study that compared liquid and lyophilized formulations of the candidate malaria vaccine RTS,S formulated in AS02A in 34 ...healthy, malaria-naïve adults at WRAIR. Volunteers received two doses of either formulation on a 0, 1-month schedule. Both vaccines were well tolerated and similarly immunogenic. Nineteen of 25 subjects who received the lyophilized formulation and six infectivity controls underwent sporozoite challenge to assess vaccine efficacy. All six controls had parasitemia detectable by thick blood smear by day 13 (mean pre-patent period 12.3 days; range 11–13). In the vaccine group, 8 of 19 vaccinees did not develop malaria and were completely protected (i.e., 42%). Among the 11 vaccinees who did become infected, the mean pre-patent period was delayed (14.4 days; range 13–18). The two formulations of RTS,S were equally safe and immunogenic, and the lyophilized formulation showed similar levels of efficacy against sporozoite challenge to that conferred by the liquid formulation in previous studies.
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