Lipid nanoparticles with accessible nickel as a vaccine delivery system for single and multiple his-tagged HIV antigens

Lipid-based nanoparticles (NPs) with a small amount of surface-chelated nickel (Ni-NPs) were developed to easily formulate the human immunodeficiency virus (HIV) his-tagged Tat (his-Tat) protein, as well as to formulate and co-deliver two HIV antigens (his-p24 and his-Nef) on one particle. Female BALB/c mice were immunized by subcutaneous injection with his-Tat/Ni-NP formulation (1.5 μg his-Tat/mouse) and control formulations on day 0 and 14. The day 28 anti-Tat specific immunoglobulin G titer with his-Tat/Ni-NPs was significantly greater than that with Alum/his-Tat. Furthermore, splenocytes from his-Tat/Ni-NP-immunized mice secreted significantly higher IFN-γ than those from mice immunized with Alum/his-Tat. Although Ni-NPs did not show better adjuvant activity than Tat-coated anionic NPs made with sodium dodecyl sulfate (SDS/NPs), they were less toxic than SDS/NPs. The initial results indicated that co-immunization of mice using his-p24/his-Nef/Ni-NP induced greater antibody response compared to using Alum/his-p24/his-Nef. Co-delivery of two antigens using Ni-NPs also increased the immunogenicity of individual antigens compared to delivery of a single antigen by Ni-NPs. In conclusion, Ni-NPs are an efficient delivery system for HIV vaccines including both single antigen delivery and multiple antigen co-delivery

Errorless learning and the cognitive rehabilitation of memory-impaired schizophrenic patients

Background. In recent years, evidence has accumulated that a significant proportion of schizophrenic patients have severe memory impairment, which cannot be attributed to the effects of medication, chronicity or institutionalization. Our group has demonstrated that memory impairment is associated with poor psychosocial outcome and treatment resistance. Work on the classical amnesic syndrome has suggested that memory training is facilitated by adopting an ‘errorless learning’ approach, where subjects do not experience failure during learning. This is based on the theory that the preserved implicit memory of amnesic patients results in implicitly remembered incorrect responses interfering with target items, in the absence of a functioning explicit memory system to allow differentiation. Method. We compared three groups of subjects, memory-impaired schizophrenic patients, memory unimpaired schizophrenic patients and healthy controls. Results. An errorless learning approach conferred a significant advantage on the memory-impaired schizophrenic group, bringing their performance up to the level of both control groups. In contrast, adopting a traditional trial and error, or errorful approach resulted in markedly impaired performance in the memory-impaired schizophrenic group only. Conclusions. We conclude that errorless learning approaches may be worthy of further evaluation in the cognitive rehabilitation of memory-impaired schizophrenic patients

Tresyl-based conjugation of protein antigen to lipid nanoparticles increases antigen immunogenicity

The present studies were aimed at investigating the engineering of NPs with protein-conjugated-surfactant at their surface. In order to increase the immunogenicity of a protein antigen, Brij 78 was functionalized by tresyl chloride and then further reacted with the primary amine of the model proteins ovalbumin (OVA) or horseradish peroxide (HRP). The reaction yielded Brij 78-OVA and Brij 78-HRP conjugates which were then used directly to form NP-OVA or NP-HRP using a one-step warm oil-in-water microemulsion precursor method with emulsifying wax as the oil phase, and Brij 78 and the Brij 78-OVA or Brij 78-HRP conjugate as surfactants. Similarly, Brij 700 was conjugated to HIV p24 antigen to yield Brij 700-p24 conjugate. The utility of these NPs for enhancing the immune responses to protein-based vaccines was evaluated in vivo using ovalbumin (OVA) as model protein and p24 as a relevant HIV antigen. In separate in vivo studies, female BALB/c mice were immunized by subcutaneous (s.c.) injection with NP-OVA and NP-p24 formulations along with several control formulations. These results suggested that with multiple antigens, covalent attachment of the antigen to the NP significantly enhanced antigen-specific immune responses. This facile covalent conjugation and incorporation method may be utilized to further incorporate other protein antigens, even multiple antigens, into an enhanced vaccine delivery system

Curriculum-based outdoor learning for children aged 9-11: A qualitative analysis of pupils’ and teachers’ views

The relationship between child health, wellbeing and education demonstrates that healthier and happier children achieve higher educational attainment. An engaging curriculum that facilitates children in achieving their academic potential has strong implications for educational outcomes, future employment prospects, and health and wellbeing during adulthood. Outdoor learning is a pedagogical approach used to enrich learning, enhance school engagement and improve pupil health and wellbeing. However, its non-traditional means of achieving curricular aims are not yet recognised beyond the early years by education inspectorates. This requires evidence into its acceptability from those at the forefront of delivery. This study aimed to explore headteachers’, teachers’ and pupils’ views and experiences of an outdoor learning programme within the key stage two curriculum (ages 9–11) in South Wales, United Kingdom. We examine the process of implementation to offer case study evidence through 1:1 interviews with headteachers (n = 3) and teachers (n = 10) and focus groups with pupils aged 9–11 (n = 10) from three primary schools. Interviews and focus groups were conducted at baseline and six months into implementation. Schools introduced regular outdoor learning within the curriculum. This study found a variety of perceived benefits for pupils and schools. Pupils and teachers noticed improvements in pupils’ engagement with learning, concentration and behaviour, as well as positive impacts on health and wellbeing and teachers’ job satisfaction. Curriculum demands including testing and evidencing work were barriers to implementation, in addition to safety concerns, resources and teacher confidence. Participants supported outdoor learning as a curriculum-based programme for older primary school pupils. However, embedding outdoor learning within the curriculum requires education inspectorates to place higher value on this approach in achieving curricular aims, alongside greater acknowledgment of the wider benefits to children which current measurements do not capture

Support and Assessment for Fall Emergency Referrals (SAFER 1) trial protocol. Computerised on-scene decision support for emergency ambulance staff to assess and plan care for older people who have fallen: evaluation of costs and benefits using a pragmatic cluster randomised trial

Background: Many emergency ambulance calls are for older people who have fallen. As half of them are left at home, a community-based response may often be more appropriate than hospital attendance. The SAFER 1 trial will assess the costs and benefits of a new healthcare technology - hand-held computers with computerised clinical decision support (CCDS) software - to help paramedics decide who needs hospital attendance, and who can be safely left at home with referral to community falls services. Methods/Design: Pragmatic cluster randomised trial with a qualitative component. We shall allocate 72 paramedics ('clusters') at random between receiving the intervention and a control group delivering care as usual, of whom we expect 60 to complete the trial. Patients are eligible if they are aged 65 or older, live in the study area but not in residential care, and are attended by a study paramedic following an emergency call for a fall. Seven to 10 days after the index fall we shall offer patients the opportunity to opt out of further follow up. Continuing participants will receive questionnaires after one and 6 months, and we shall monitor their routine clinical data for 6 months. We shall interview 20 of these patients in depth. We shall conduct focus groups or semi-structured interviews with paramedics and other stakeholders. The primary outcome is the interval to the first subsequent reported fall (or death). We shall analyse this and other measures of outcome, process and cost by 'intention to treat'. We shall analyse qualitative data thematically. Discussion: Since the SAFER 1 trial received funding in August 2006, implementation has come to terms with ambulance service reorganisation and a new national electronic patient record in England. In response to these hurdles the research team has adapted the research design, including aspects of the intervention, to meet the needs of the ambulance services. In conclusion this complex emergency care trial will provide rigorous evidence on the clinical and cost effectiveness of CCDS for paramedics in the care of older people who have fallen

Infrastructure transformation as a socio-technical process - Implications for the governance of energy distribution networks in the UK

This paper seeks to uncover and examine the complex set of governance challenges associated with transforming energy distribution networks, which play a key enabling role in a low carbon energy transition. We argue that, although the importance of such infrastructure networks to sustainability and low carbon transitions in the energy, water and mobility sectors is clear, there is relatively little understanding of the social and institutional dimension of these systems and appropriate governance strategies for their transformation. This may be because the prevalent model of infrastructure governance in the energy and other sectors has prioritised short term time horizons and static efficiencies. In this paper we draw on the social shaping of technology literature to develop a broader understanding of infrastructure change as a dynamic socio-technical process. The empirical focus of the paper is on the development of more flexible and sustainable energy distribution systems as key enablers for the UK's low carbon transition. Focusing on electricity and heat networks we identify a range of governance challenges along different phases of the 'infrastructure lifecycle', and we draw lessons for the development of governance frameworks for the transformation of energy infrastructure more generally

Domestication-induced reduction in eye size revealed in multiple common garden experiments: The case of Atlantic salmon (Salmo salar L.)

Domestication leads to changes in traits that are under directional selection in breeding programmes, though unintentional changes in nonproduction traits can also arise. In offspring of escaping fish and any hybrid progeny, such unintentionally altered traits may reduce fitness in the wild. Atlantic salmon breeding programmes were established in the early 1970s, resulting in genetic changes in multiple traits. However, the impact of domestication on eye size has not been studied. We measured body size corrected eye size in 4000 salmon from six common garden experiments conducted under artificial and natural conditions, in freshwater and saltwater environments, in two countries. Within these common gardens, offspring of domesticated and wild parents were crossed to produce 11 strains, with varying genetic backgrounds (wild, domesticated, F1 hybrids, F2 hybrids and backcrosses). Size-adjusted eye size was influenced by both genetic and environmental factors. Domesticated fish reared under artificial conditions had smaller adjusted eye size when compared to wild fish reared under identical conditions, in both the freshwater and marine environments, and in both Irish and Norwegian experiments. However, in parr that had been introduced into a river environment shortly after hatching and sampled at the end of their first summer, differences in adjusted eye size observed among genetic groups were of a reduced magnitude and were nonsignificant in 2-year-old sea migrating smolts sampled in the river immediately prior to sea entry. Collectively, our findings could suggest that where natural selection is present, individuals with reduced eye size are maladapted and consequently have reduced fitness, building on our understanding of the mechanisms that underlie a well-documented reduction in the fitness of the progeny of domesticated salmon, including hybrid progeny, in the wild

Paramedic assessment of older adults after falls, including community care referral pathway : cluster randomized trial

Study objective We aim to determine clinical and cost-effectiveness of a paramedic protocol for the care of older people who fall. Methods We undertook a cluster randomized trial in 3 UK ambulance services between March 2011 and June 2012. We included patients aged 65 years or older after an emergency call for a fall, attended by paramedics based at trial stations. Intervention paramedics could refer the patient to a community-based falls service instead of transporting the patient to the emergency department. Control paramedics provided care as usual. The primary outcome was subsequent emergency contacts or death. Results One hundred five paramedics based at 14 intervention stations attended 3,073 eligible patients; 110 paramedics based at 11 control stations attended 2,841 eligible patients. We analyzed primary outcomes for 2,391 intervention and 2,264 control patients. One third of patients made further emergency contacts or died within 1 month, and two thirds within 6 months, with no difference between groups. Subsequent 999 call rates within 6 months were lower in the intervention arm (0.0125 versus 0.0172; adjusted difference –0.0045; 95% confidence interval –0.0073 to –0.0017). Intervention paramedics referred 8% of patients (204/2,420) to falls services and left fewer patients at the scene without any ongoing care. Intervention patients reported higher satisfaction with interpersonal aspects of care. There were no other differences between groups. Mean intervention cost was $23 per patient, with no difference in overall resource use between groups at 1 or 6 months. Conclusion A clinical protocol for paramedics reduced emergency ambulance calls for patients attended for a fall safely and at modest cost

Guelb el Ahmar (Bathonian, Anoual Syncline, eastern Morocco): First continental flora and fauna including mammals from the Middle Jurassic of Africa

We report the discovery in Mesozoic continental “red beds” of Anoual Syncline, Morocco, of the new Guelb el Ahmar (GEA) fossiliferous sites in the Bathonian Anoual Formation. They produced one of the richest continental biotic assemblages from the Jurassic of Gondwana, including plants, invertebrates and vertebrates. Both the sedimentological facies and the biotic assemblage indicate a lacustrine depositional environment. The flora is represented by tree trunks (three families), pollen (13 species, five major clades) and charophytes. It suggests local forests and humid (non-arid) conditions. The vertebrate fauna is dominated by microvertebrates recovered by screening–washing. It is rich and diverse, with at least 29 species of all major groups (osteichthyans, lissamphibians, chelonians, diapsids, mammals), except chondrichthyans. It includes the first mammals discovered in the Middle Jurassic of Arabo-Africa. The GEA sites yielded some of the earliest known representatives of osteoglossiform fishes, albanerpetontid and caudate amphibians, squamates (scincomorphans, anguimorphan), cladotherian mammals, and likely choristoderes. The choristoderes, if confirmed, are the first found in Gondwana, the albanerpetontid and caudatan amphibians are among the very few known in Gondwana, and the anguimorph lizard is the first known from the Mesozoic of Gondwana. Mammals (Amphitheriida, cf. Dryolestida) remain poorly known, but are the earliest cladotherians known in Gondwana. The GEA biotic assemblage is characterized by the presence of Pangean and Laurasian (especially European) taxa, and quasi absence of Gondwanan taxa. The paleobiogeographical analysis suggests either a major fossil bias in Gondwana during the Middle Jurassic, and an overall vicariant Pangean context for the GEA assemblage, or alternatively, noticeable Laurasian (European) affinities and North-South dispersals. The close resemblance between the Bathonian faunas of GEA and Britain is remarkable, even in a Pangean context. The similarity between the local Anoual Syncline Guelb el Ahmar and Ksar Metlili faunas raises questions on the ?Berriasian age of the latter