Randomized, Controlled Trial of the Long Term Safety, Immunogenicity and Efficacy of RTS,S/AS02(D) Malaria Vaccine in Infants Living in a Malaria-Endemic Region.

The RTS,S/AS malaria candidate vaccine is being developed with the intent to be delivered, if approved, through the Expanded Programme on Immunization (EPI) of the World Health Organization. Safety, immunogenicity and efficacy of the RTS,S/AS02(D) vaccine candidate when integrated into a standard EPI schedule for infants have been reported over a nine-month surveillance period. This paper describes results following 20 months of follow up. This Phase IIb, single-centre, randomized controlled trial enrolled 340 infants in Tanzania to receive three doses of RTS,S/AS02(D) or hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received DTPw/Hib (diphtheria and tetanus toxoids, whole-cell pertussis vaccine, conjugated Haemophilus influenzae type b vaccine) at the same timepoints. The study was double-blinded to month 9 and single-blinded from months 9 to 20. From month 0 to 20, at least one SAE was reported in 57/170 infants who received RTS,S/AS02(D) (33.5%; 95% confidence interval [CI]: 26.5, 41.2) and 62/170 infants who received hepatitis B vaccine (36.5%; 95% CI: 29.2, 44.2). The SAE profile was similar in both vaccine groups; none were considered to be related to vaccination. At month 20, 18 months after completion of vaccination, 71.8% of recipients of RTS,S/AS02(D) and 3.8% of recipients of hepatitis B vaccine had seropositive titres for anti-CS antibodies; seroprotective levels of anti-HBs antibodies remained in 100% of recipients of RTS,S/AS02(D) and 97.7% recipients of hepatitis B vaccine. Anti-HBs antibody GMTs were higher in the RTS,S/AS02(D) group at all post-vaccination time points compared to control. According to protocol population, vaccine efficacy against multiple episodes of malaria disease was 50.7% (95% CI: -6.5 to 77.1, p = 0.072) and 26.7% (95% CI: -33.1 to 59.6, p = 0.307) over 12 and 18 months post vaccination, respectively. In the Intention to Treat population, over the 20-month follow up, vaccine efficacy against multiple episodes of malaria disease was 14.4% (95% CI: -41.9 to 48.4, p = 0.545). The acceptable safety profile and good tolerability of RTS,S/AS02(D) in combination with EPI vaccines previously reported from month 0 to 9 was confirmed over a 20 month surveillance period in this infant population. Antibodies against both CS and HBsAg in the RTS,S/AS02(D) group remained significantly higher compared to control for the study duration. Over 18 months follow up, RTS,S/AS02(D) prevented approximately a quarter of malaria cases in the study population. CLINICAL TRIALS: Gov identifier: NCT00289185

Evaluation of the Safety and Immunogenicity of the RTS,S/AS01E Malaria Candidate Vaccine When Integrated in the Expanded Program of Immunization

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

Virosome-Formulated Plasmodium falciparum AMA-1 & CSP Derived Peptides as Malaria Vaccine: Randomized Phase 1b Trial in Semi-Immune Adults & Children

BACKGROUND\ud \ud This trial was conducted to evaluate the safety and immunogenicity of two virosome formulated malaria peptidomimetics derived from Plasmodium falciparum AMA-1 and CSP in malaria semi-immune adults and children.\ud \ud METHODS\ud \ud The design was a prospective randomized, double-blind, controlled, age-deescalating study with two immunizations. 10 adults and 40 children (aged 5-9 years) living in a malaria endemic area were immunized with PEV3B or virosomal influenza vaccine Inflexal®V on day 0 and 90.\ud \ud RESULTS\ud \ud No serious or severe adverse events (AEs) related to the vaccines were observed. The only local solicited AE reported was pain at injection site, which affected more children in the Inflexal®V group compared to the PEV3B group (p = 0.014). In the PEV3B group, IgG ELISA endpoint titers specific for the AMA-1 and CSP peptide antigens were significantly higher for most time points compared to the Inflexal®V control group. Across all time points after first immunization the average ratio of endpoint titers to baseline values in PEV3B subjects ranged from 4 to 15 in adults and from 4 to 66 in children. As an exploratory outcome, we found that the incidence rate of clinical malaria episodes in children vaccinees was half the rate of the control children between study days 30 and 365 (0.0035 episodes per day at risk for PEV3B vs. 0.0069 for Inflexal®V; RR  = 0.50 [95%-CI: 0.29-0.88], p = 0.02).\ud \ud CONCLUSION\ud \ud These findings provide a strong basis for the further development of multivalent virosomal malaria peptide vaccines.\ud \ud TRIAL REGISTRATION\ud \ud ClinicalTrials.gov NCT00513669

Multiplication of microbes below 0.690 water activity: implications for terrestrial and extraterrestrial life

Since a key requirement of known life-forms is available water (water-activity; aw), searches for signatures of past life in terrestrial and extraterrestrial environments have recently targeted places known to have contained significant quantities of biologically available water. The lower limit of water activity that enables cell division is ~0.605 which, until now, was only known to be exhibited by a single eukaryote; the sugar-tolerant, fungal xerophile Xeromyces bisporus. The first forms of life on Earth were, however, prokaryotic. Furthermore, early life on Earth inhabited high-salt environments, suggesting an ability to withstand low water activity. Recent evidence indicates that some halophilic Archaea and Bacteria have water activity limits more or less equal to those of X. bisporus. Regardless of species, cellular systems are sensitive to minute differences in water activity (of w-units) so there is a need to determine water-activity values to three decimal places. We discuss water activity in relation to the limits of Earth’s present-day biosphere; the possibility of microbial multiplication by utilizing water from thin, aqueous films or non-liquid sources; whether prokaryotes were the first organisms able to multiply at the 0.605-aw limit; and whether extraterrestrial aqueous milieu of ≥0.605 aw can resemble fertile microbial habitats found on Earth

Theoretical study of structural and thermodynamic properties of gaseous metal hydrides m2xh4 (m = li, na; x = be, mg)

A Dissertation Submitted in Partial Fulfilment of the Requirements for the Degree of Master’s in Materials Science and Engineering of the Nelson Mandela African Institution of Science and TechnologyThis study aimed to explore the properties of the complex hydrides which seem to be the promising candidates for hydrogen storage materials. The geometrical structure, vibrational spectra and thermodynamic characteristics of the gaseous complex hydrides, MXH3 and M2XH4 (M = Li, Na; X = Be, Mg) and the subunits LiH, NaH, Li2H+, Li2H+, Li2H2, Na2H2, BeH2, MgH2, MgH3−, BeH3− have been investigated. Quantum chemical methods of density functional theory and second order Moller−Plesset perturbation theory have been applied. According to the calculations, three isomers of M2XH4 have been proved to exist, polyhedral of C2v symmetry; two−cycled, D2d and hexagonal shape, C2v. For M2BeH4 polyhedral isomer was found to have the lowest energy and for M2MgH4 was cyclic hexagonal configuration. The abundance of the isomers in vapour was evaluated and the hexagonal isomer was observed to prevail in vapour both for beryllium and magnesium complexes. For smaller hydrides, MXH3, the cyclic equilibrium structure (C2v) was shown to exist, another possible configuration, the linear one (C∞v) was found to be of much higher energy (~130 kJ mol–1). Different pathways of gas−phase and heterophase dissociation reactions were examined; the enthalpies of formation of the complex hydrides were found; 105 ± 26 (LiBeH3), 63 ± 37 (Li2BeH4), 121 ± 27 (NaBeH3), 117 ± 39 (Na2BeH4), 114 ± 13 (LiMgH3), 113 ±12 (Li2MgH4), 162 ± 11 (NaMgH3), and 175 ± 26 (Na2MgH4) (in kJ mol 1). The assessment of thermal stability of the hydrides was done through Gibbs free energies for heterophase decomposition

Uwiano na Utofauti wa Kiisimu Kati ya Kiswahili cha Paje na Makunduchi

Utafiti huu uliangazia uwiano na utofauti wa kiisimu kati ya Kiswahili cha Paje na Makunduchi. Na ulikuwa na malengo matatu; Kubainisha mfanano na utofauti baina ya fonimu za Kiswahili cha Paje na Makunduchi, pili Kulinganisha na kutofautisha kanuni za kifonolojia na mofolojia zinazotawala mofu ziundazo maneno ya Kiswahili cha Paje na Makunduchi na Kubainisha uwiano na utofautiano wa kimaana baina ya msamiati wa Kiswahili cha Paje na Makunduchi. Ili kufikia malengo yaliyokusudiwa mbinu za usaili, hojaji, ushuhudiaji na Maktabani zilitumika, hata hivyo utafiti huu uliongozwa na nadharia mbili; isimu linganishi na Mofofonolojia pamoja na sampuli ya watoa taarifa sitini (60) ilitumika thelathini kutoka Paje na thelathini kwa Makunduchi. Kupitia matokeo ya utafiti, imegundulika kuwa Kifonolojia jamii hizi zinatofautiana kifonimi hasa kiidadi na kimatumizi kwa baadhi ya fonimu hizo. Pia, imebainika kuwa Kimakunduchi na Kipaje vinatofautiana katika baadhi ya kanuni za fonolojia na mofolojia kama vile katika udondoshaji na uyeyushaji katika baadhi ya nomino, vitenzi na vivumishi vimilikishi. Pia imebaainika kuwa Kimakunduchi na Kipaje vinatofautiana katika umiliki wa alomofu za nafsi ya kwanza na ya pili pamoja na viambishi vya ung'oekaji wa o-rejeshi, pamoja na hayo imebainika kuwa jamii hizi zinatofautiana kimaana katika baadhi ya maneno na hivyo imeonekana kuwa Wapaje wameathiriwa na Kiswahili sanifu katika utoaji na uwakilishi wa maana zao. Mwisho mtafiti amependekeza mambo kadhaa kwa watafiti wajao, mambo hayo ni pamoja na tafiti nyingine linganishi zifanyike kwa baadhi ya vipengele vya fonolojia vipande kama vile silabi, fonolojia arudhi pamoja na kipengele cha sintaksia. Pili tumebaini kuwa Kimakunduchi kina vilahaja zaidi ya kimoja hivyo mtafiti anapendekeza eneo hili ni vizuri likafanyiwa uchunguzi wa kiutafiti zaidi

Sources, survival and transmission of Cryptosporiopsis sp., leaf and nut blight pathogen of cashew (Anacardium occidentale Linn)

The germination of conidia was studied from 2 hours to 16 hours after incubation at an interval of two hours period. The germination of macroconidia microscopically was followed to understand the timing of key events. Ten infected cashew nuts were placed each on a Petri dish containing malt extract agar and incubated at 27 °C for 10 days. Cryptosporiopsis sp. pathogen was detected in nut samples of cashew clones. Leaf and nut blight pathogen remained viable up to one year in plant debris stored under laboratory condition at a minimum temperature range from 4 to 5 °C. There was a rapid population decline on viable counts of Cryptosporiopsis sp. recovered from sterile and unsterile soil after various periods of time. In debris buried at a depth of 7 cm in sterile or unsterile soil they survived for four months with 8% and 5% of disease samples with viable pathogen. Saprophytic survival capacity of the fungus Cryptosporiopsis sp. in cashew field revealed that the pathogen survival was 80% up to four months of incubation but fell to 40% after 6 months. It was demonstrated that plant debris, soil and nuts could harbour sufficient inoculum to cause disease in new plants

Arab Anti-Semitism

Although anti-Semitism is a fact of Arab life, most individuals prefer to describe it as political animosity and religious polemic. This explains why my study has only drawn from works on the subject by Western historians – because no Arab historian has even acknowledged that it exists, let alone written about it. In this study I compare and analyze the different views my sources have on some matters related to the subject of Jew-hatred among Arabs; these are Zionism, the origins of Arab nationalism, the legendary age of tolerance in Al-andalus (Muslim Spain) and the treatment of Jews in the Quran. In most of my sources I find that: For Arabs, Zionism and Jewishness are one and the same thing. The influence of Nazi ideals and prejudices on Arab nationalism and the paranoid attitudes of the region’s leaders effectively stymie any chances of reconciliation between the two peoples.  Historical evidences show that the much-praised racial harmony of Al-andalus has been exaggerated for political purposes. The negative image of Jews in the Quran has been deliberately misinterpreted in order to keep hatred of Jews alive among Arabs today. To see just how effective anti-Semitic indoctrination has been on reasonable, educated people, I sent a simple question to my Arab friends around the world asking them to say what they really think of Jews, hoping to get some candid answers.  But to my great disappointment, not one of them replied

Diario de Burgos : de avisos y noticias: Año LV Número 16852 - 1945 mayo 18

Copia digital. España : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 201