97 research outputs found
Safety and immunogenicity of the chlamydia vaccine candidate CTH522 adjuvanted with CAF01 liposomes or aluminium hydroxide: a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial
BACKGROUND: Chlamydia is the most common sexually transmitted bacterial infection worldwide. National screening programmes and antibiotic treatment have failed to decrease incidence, and to date no vaccines against genital chlamydia have been tested in clinical trials. We aimed to assess the safety and immunogenicity, in humans, of a novel chlamydia vaccine based on a recombinant protein subunit (CTH522) in a prime-boost immunisation schedule. METHODS: This phase 1, first-in-human, double-blind, parallel, randomised, placebo-controlled trial was done at Hammersmith Hospital in London, UK, in healthy women aged 19-45 years. Participants were randomly assigned (3:3:1) to three groups: CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01), CTH522 adjuvanted with aluminium hydroxide (CTH522:AH), or placebo (saline). Participants received three intramuscular injections of 85 μg vaccine (with adjuvant) or placebo to the deltoid region of the arm at 0, 1, and 4 months, followed by two intranasal administrations of 30 μg unadjuvanted vaccine or placebo (one in each nostril) at months 4·5 and 5·0. The primary outcome was safety and the secondary outcome was humoral immunogenicity (anti-CTH522 IgG seroconversion). This study is registered with Clinicaltrials.gov, number NCT02787109. FINDINGS: Between Aug 15, 2016, and Feb 13, 2017, 35 women were randomly assigned (15 to CTH522:CAF01, 15 to CTH522:AH, and five to placebo). 32 (91%) received all five vaccinations and all participants were included in the intention-to-treat analyses. No related serious adverse reactions were reported, and the most frequent adverse events were mild local injection-site reactions, which were reported in all (15 [100%] of 15) participants in the two vaccine groups and in three (60%) of five participants in the placebo group (p=0·0526 for both comparisons). Intranasal vaccination was not associated with a higher frequency of related local reactions (reported in seven [47%] of 15 participants in the active treatment groups vs three [60%] of five in the placebo group; p=1·000). Both CTH522:CAF01 and CTH522:AH induced anti-CTH522 IgG seroconversion in 15 (100%) of 15 participants after five immunisations, whereas no participants in the placebo group seroconverted. CTH522:CAF01 showed accelerated seroconversion, increased IgG titres, an enhanced mucosal antibody profile, and a more consistent cell-mediated immune response profile compared with CTH522:AH. INTERPRETATION: CTH522 adjuvanted with either CAF01 or aluminium hydroxide appears to be safe and well tolerated. Both vaccines were immunogenic, although CTH522:CAF01 had a better immunogenicity profile, holding promise for further clinical development. FUNDING: European Commission and The Innovation Fund Denmark
Assessment at UK medical schools varies substantially in volume, type and intensity and correlates with postgraduate attainment
BACKGROUND: In the United Kingdom (UK), medical schools are free to develop local systems and policies that govern student assessment and progression. Successful completion of an undergraduate medical degree results in the automatic award of a provisional licence to practice medicine by the General Medical Council (GMC). Such a licensing process relies heavily on the assumption that individual schools develop similarly rigorous assessment policies. Little work has evaluated variability of undergraduate medical assessment between medical schools. That absence is important in the light of the GMC's recent announcement of the introduction of the UKMLA (UK Medical Licensing Assessment) for all doctors who wish to practise in the UK. The present study aimed to quantify and compare the volume, type and intensity of summative assessment across medicine (A100) courses in the United Kingdom, and to assess whether intensity of assessment correlates with the postgraduate attainment of doctors from these schools. METHODS: Locally knowledgeable students in each school were approached to take part in guided-questionnaire interviews via telephone or Skype(TM). Their understanding of assessment at their medical school was probed, and later validated with the assessment department of the respective medical school. We gathered data for 25 of 27 A100 programmes in the UK and compared volume, type and intensity of assessment between schools. We then correlated these data with the mean first-attempt score of graduates sitting MRCGP and MRCP(UK), as well as with UKFPO selection measures. RESULTS: The median written assessment volume across all schools was 2000 min (mean = 2027, SD = 586, LQ = 1500, UQ = 2500, range = 1000-3200) and 1400 marks (mean = 1555, SD = 463, LQ = 1200, UQ = 1800, range = 1100-2800). The median practical assessment volume was 400 min (mean = 472, SD = 207, LQ = 400, UQ = 600, range = 200-1000). The median intensity (minutes per mark ratio) of summative written assessment was 1.24 min per mark (mean = 1.28, SD = 0.30, LQ = 1.11, UQ = 1.37, range = 0.85-2.08). An exploratory analysis suggested a significant correlation of total assessment time with mean first-attempt score on both the knowledge and the clinical assessments of MRCGP and of MRCP(UK). CONCLUSIONS: There are substantial differences in the volume, format and intensity of undergraduate assessment between UK medical schools. These findings suggest a potential for differences in the reliability of detecting poorly performing students, or differences in identifying and stratifying academically equivalent students for ranking in the Foundation Programme Application System (FPAS). Furthermore, these differences appear to directly correlate with performance in postgraduate examinations. Taken together, our findings highlight highly variable local assessment procedures that warrant further investigation to establish their potential impact on students
Transient Facial Nerve Paralysis (Bell's Palsy) following Intranasal Delivery of a Genetically Detoxified Mutant of Escherichia coli Heat Labile Toxin
BACKGROUND: An association was previously established between facial nerve paralysis (Bell's palsy) and intranasal administration of an inactivated influenza virosome vaccine containing an enzymatically active Escherichia coli Heat Labile Toxin (LT) adjuvant. The individual component(s) responsible for paralysis were not identified, and the vaccine was withdrawn.
METHODOLOGY/PRINCIPAL FINDINGS: Subjects participating in two contemporaneous non-randomized Phase 1 clinical trials of nasal subunit vaccines against Human Immunodeficiency Virus and tuberculosis, both of which employed an enzymatically inactive non-toxic mutant LT adjuvant (LTK63), underwent active follow-up for adverse events using diary-cards and clinical examination. Two healthy subjects experienced transient peripheral facial nerve palsies 44 and 60 days after passive nasal instillation of LTK63, possibly a result of retrograde axonal transport after neuronal ganglioside binding or an inflammatory immune response, but without exaggerated immune responses to LTK63.
CONCLUSIONS/SIGNIFICANCE: While the unique anatomical predisposition of the facial nerve to compression suggests nasal delivery of neuronal-binding LT-derived adjuvants is inadvisable, their continued investigation as topical or mucosal adjuvants and antigens appears warranted on the basis of longstanding safety via oral, percutaneous, and other mucosal routes
Food Use and Health Effects of Soybean and Sunflower Oils
This review provides a scientific assessment of current knowledge of health effects of soybean oil (SBO) and sunflower oil (SFO). SBO and SFO both contain high levels of polyunsaturated fatty acids (PUFA) (60.8 and 69%, respectively), with a PUFA:saturated fat ratio of 4.0 for SBO and 6.4 for SFO. SFO contains 69% C18:2n-6 and less than 0.1% C18:3n-3, while SBO contains 54% C18:2n-6 and 7.2% C18:3n-3. Thus, SFO and SBO each provide adequate amounts of C18:2n-6, but of the two, SBO provides C18:3n-3 with a C18:2n-6:C18:3n-3 ratio of 7.1. Epidemiological evidence has suggested an inverse relationship between the consumption of diets high in vegetable fat and blood pressure, although clinical findings have been inconclusive. Recent dietary guidelines suggest the desirability of decreasing consumption of total and saturated fat and cholesterol, an objective that can be achieved by substituting such oils as SFO and SBO for animal fats. Such changes have consistently resulted in decreased total and low-density-lipoprotein cholesterol, which is thought to be favorable with respect to decreasing risk of cardiovascular disease. Also, decreases in high-density-lipoprotein cholesterol have raised some concern. Use of vegetable oils such as SFO and SBO increases C18:2n-6, decreases C20:4n-6, and slightly elevated C20:5n-3 and C22:6n-3 in platelets, changes that slightly inhibit platelet generation of thromboxane and ex vivo aggregation. Whether chronic use of these oils will effectively block thrombosis at sites of vascular injury, inhibit pathologic platelet vascular interactions associated with atherosclerosis, or reduce the incidence of acute vascular occlusion in the coronary or cerebral circulation is uncertain. Linoleic acid is needed for normal immune response, and essential fatty acid (EFA) deficiency impairs B and T cell-mediated responses. SBO and SFO can provide adequate linoleic acid for maintenance of the immune response. Excess linoleic acid has supported tumor growth in animals, an effect not verified by data from diverse human studies of risk, incidence, or progression of cancers of the breast and colon. Areas yet to be investigated include the differential effects of n-6- and n-3-containing oil on tumor development in humans and whether shorter-chain n-3 PUFA of plant origin such as found in SBO will modulate these actions of linoleic acid, as has been shown for the longer-chain n-3 PUFA of marine oil
Agroecological settings and seed recycling account only partially for potato seed degeneration in Ecuador
Potato production in low-income countries is threatened by seed degeneration, i.e., the accumulation of seed-borne diseases and pests in potato seed tubers when these are vegetatively propagated over consecutive cycles, leading to a reduction in seed quality and yielding ability. Agroecological settings and seed recycling (on-farm propagation over consecutive cycles) determine the process of seed degeneration. However, it is poorly understood how these factors affect this process. Therefore, to reduce this knowledge gap, we analysed two datasets collected in Ecuador, one from a multi-annual field experiment and one from a farmers’ seed study. The experiment, carried out from 2013 to 2016, aimed to assess seed degeneration at agroecological settings present in three different altitudes. The farmers’ seed study, in which 260 farmers were surveyed in 2018, aimed to understand potato seed degeneration in farmers’ fields under diverse agroecological settings. Our results of the multi-annual field experiment showed that agroecological settings have a heterogeneous influence on the presence of seed-borne diseases and pests. We also found that both the agroecological settings at the three altitudes and the number of on-farm propagation cycles affected the rates at which seed-borne diseases and pests on the seeds increased and yield decreased. However, the farmers’ seed study challenged these results by indicating that this was not clear on farms. Combining these results, this article shows that agroecological settings and seed recycling only partially explain the process of seed degeneration. This suggests that more research about seed degeneration needs to also take place under farmers’ conditions to fully understand the complex of potato performance factors. We expect that such research will support the design of improved seed interventions, while simultaneously it may generate discussion about when potato seed degeneration plays an important role in productivity
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