Publications by authors named "J Kevin Harrison"

3,646 Publications

  • Page 1 of 1

The structure of an infectious immature flavivirus redefines viral architecture and maturation.

Sci Adv 2021 May 14;7(20). Epub 2021 May 14.

Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.

Flaviviruses are the cause of severe human diseases transmitted by mosquitoes and ticks. These viruses use a potent fusion machinery to enter target cells that needs to be restrained during viral assembly and egress. A molecular chaperone, premembrane (prM) maintains the virus particles in an immature, fusion-incompetent state until they exit the cell. Taking advantage of an insect virus that produces particles that are both immature and infectious, we determined the structure of the first immature flavivirus with a complete spike by cryo-electron microscopy. Unexpectedly, the prM chaperone forms a supporting pillar that maintains the immature spike in an asymmetric and upright state, primed for large rearrangements upon acidification. The collapse of the spike along a path defined by the prM chaperone is required, and its inhibition by a multivalent immunoglobulin M blocks infection. The revised architecture and collapse model are likely to be conserved across flaviviruses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abe4507DOI Listing
May 2021

Whole School SEND (WSS) Review: study protocol for a two-arm pragmatic parallel cluster randomised controlled trial in 160 English secondary schools.

Trials 2021 May 10;22(1):333. Epub 2021 May 10.

Policy Evaluation and Research Unit, Manchester Metropolitan University, Manchester, UK.

Background: The trial will study the effects of the Whole School SEND Review on secondary school pupils in English mainstream education, to understand the impact of the intervention on academic attainment, wellbeing, and school attendance. The Review is designed to facilitate whole-school change through providing enhanced, intensive and sustained support and training in inclusive education for school special educational needs coordinators and leadership teams. The trial will have a specific focus on pupils designated as having special educational needs or disabilities.

Methods: We recruited 160 English secondary schools (approx. 58,000 pupils across two cohorts) to a two-arm pragmatic parallel cluster randomised controlled trial, with allocation at the school level. Randomisation will be stratified by school region. The primary outcome is attainment in English language (using standardised national test results at 16 years) for pupils designated as having a special educational need (approx. 4000 pupils). Secondary outcomes will be measured for pupils both with and without a special educational need designation and include pupil wellbeing (measured using the Strengths and Difficulties Questionnaire), absences and exclusions, and attainment in Mathematics and English language at 16 years. The intervention will be implemented from July 2021 and analysis of outcomes (for the year 9 cohort) will take place in September 2023, with further analysis (for the year 8 cohort) in September 2024 if the evaluation shows that acceptable implementation fidelity has been achieved.

Discussion: Pupils with special educational needs represent a significant and often vulnerable part of the secondary school population, are disproportionately likely to be excluded from school, eligible for free school meals, or supported by children's social care. Despite these multiple important areas of need, school leaders report substantial challenges in making additional provision for this group. Previous research has highlighted the development of inclusive school cultures (rather focusing primarily on targeted individualised approaches) as being important. This trial will investigate how an intervention designed to drive whole school change may lead to outcomes for pupils with and without a special educational needs designation. As such, this trial is expected to make an important contribution to research evidence and to UK educational policy.

Trial Registration: ISRCTN registry ISRCTN11339306 . Registered on 12 March 2020 (retrospectively registered).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13063-021-05280-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107406PMC
May 2021

A pancreatic tail mass in a young male.

Gastroenterology 2021 May 5. Epub 2021 May 5.

Department of GI and General Surgery, Massachusetts General Hospital, Boston, MA 02114.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2021.04.073DOI Listing
May 2021

A chimeric dengue virus vaccine candidate delivered by high density microarray patches protects against infection in mice.

NPJ Vaccines 2021 May 7;6(1):66. Epub 2021 May 7.

Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.

Dengue viruses (DENV) cause an estimated 390 million infections globally. With no dengue-specific therapeutic treatment currently available, vaccination is the most promising strategy for its control. A wide range of DENV vaccines are in development, with one having already been licensed, albeit with limited distribution. We investigated the immunogenicity and protective efficacy of a chimeric virus vaccine candidate based on the insect-specific flavivirus, Binjari virus (BinJV), displaying the structural prM/E proteins of DENV (BinJ/DENV2-prME). In this study, we immunized AG129 mice with BinJ/DENV2-prME via a needle-free, high-density microarray patch (HD-MAP) delivery system. Immunization with a single, 1 µg dose of BinJ/DENV2-prME delivered via the HD-MAPs resulted in enhanced kinetics of neutralizing antibody induction when compared to needle delivery and complete protection against mortality upon virus challenge in the AG129 DENV mouse model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41541-021-00328-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105366PMC
May 2021

Optimism with Caution: Elexacaftor-Tezacaftor-Ivacaftor in Patients with Advanced Pulmonary Disease.

Am J Respir Crit Care Med 2021 May 5. Epub 2021 May 5.

Royal Children's Hospital, Respiratory and Sleep Medicine, Parkville, Victoria, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.202103-0682LEDOI Listing
May 2021