Support vector regression to estimate the permeability enhancement of potential transdermal enhancers

This is the peer reviewed version of the following article: Shah, A., Sun, Y., Adams, R. G., Davey, N., Wilkinson, S. C. and Moss, G. P. (2016), Support vector regression to estimate the permeability enhancement of potential transdermal enhancers', Journal of Pharmacy and Pharmacology, Vol. 68 (2): 170–184, which has been published in final form at doi:10.1111/jphp.12508. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. © 2016 Royal Pharmaceutical Society.Objectives Searching for chemicals that will safely enhance transdermal drug delivery is a significant challenge. This study applies support vector regression (SVR) for the first time to estimating the optimal formulation design of transdermal hydrocortisone formulations. Methods The aim of this study was to apply SVR methods with two different kernels in order to estimate the enhancement ratio of chemical enhancers of permeability. Key findings A statistically significant regression SVR model was developed. It was found that SVR with a nonlinear kernel provided the best estimate of the enhancement ratio for a chemical enhancer. Conclusions Support vector regression is a viable method to develop predictive models of biological processes, demonstrating improvements over other methods. In addition, the results of this study suggest that a global approach to modelling a biological process may not necessarily be the best method and that a ‘mixed-methods’ approach may be best in optimising predictive models.Peer reviewedFinal Accepted Versio

The Ice in Voices:Understanding negative content in auditory-verbal hallucinations

Negative voice-content is the best sole predictor of whether the hearer of an auditory-verbal hallucination will experience distress/impairment necessitating contact with mental health services. Yet, what causes negative voice-content and how interventions may reduce it remains poorly understood. This paper offers definitions of negative voice content and considers what may cause negative voice-content. We propose a framework in which adverse life-events may underpin much negative voice-content, a relation which may be mediated by me- chanisms including hypervigilance, reduced social rank, shame and self-blame, dissociation, and altered emo- tional processing. At a neurological level, we note how the involvement of the amygdala and right Broca's area could drive negative voice-content. We observe that negative interactions between hearers and their voices may further drive negative voice-content. Finally, we consider the role of culture in shaping negative voice-content. This framework is intended to deepen and extend cognitive models of voice-hearing and spur further devel- opment of psychological interventions for those distressed by such voices. We note that much of the relevant research in this area remains to be performed or replicated. We conclude that more attention needs to be paid to methods for reducing negative voice-content, and urge further research in this important area

Are the Mascarene frog (Ptychadena mascareniensis) and Brahminy blind snake (Indotyphlops braminus) really alien species in the Seychelles?

This is an accepted manuscript of an article published by the British Herpetological Society in the Herpetological Bulletin on 30/09/2020. The accepted version of the publication may differ from the final published version

Climate warming, marine protected areas and the ocean-scale integrity of coral reef ecosystems

Coral reefs have emerged as one of the ecosystems most vulnerable to climate variation and change. While the contribution of a warming climate to the loss of live coral cover has been well documented across large spatial and temporal scales, the associated effects on fish have not. Here, we respond to recent and repeated calls to assess the importance of local management in conserving coral reefs in the context of global climate change. Such information is important, as coral reef fish assemblages are the most species dense vertebrate communities on earth, contributing critical ecosystem functions and providing crucial ecosystem services to human societies in tropical countries. Our assessment of the impacts of the 1998 mass bleaching event on coral cover, reef structural complexity, and reef associated fishes spans 7 countries, 66 sites and 26 degrees of latitude in the Indian Ocean. Using Bayesian meta-analysis we show that changes in the size structure, diversity and trophic composition of the reef fish community have followed coral declines. Although the ocean scale integrity of these coral reef ecosystems has been lost, it is positive to see the effects are spatially variable at multiple scales, with impacts and vulnerability affected by geography but not management regime. Existing no-take marine protected areas still support high biomass of fish, however they had no positive affect on the ecosystem response to large-scale disturbance. This suggests a need for future conservation and management efforts to identify and protect regional refugia, which should be integrated into existing management frameworks and combined with policies to improve system-wide resilience to climate variation and change

Riparian buffers can help mitigate biodiversity declines in oil palm agriculture

Agricultural expansion drives biodiversity decline in forested tropical regions. Consequently, it is important to understand the conservation value of remnant forest in production landscapes. In a tropical landscape dominated by oil palm we characterized faunal communities across eight taxa occurring within riparian forest buffers, which are legally protected alongside rivers, and compared them to nearby recovering logged forest. Buffer width was the main predictor of species richness and abundance, with widths of 40-100 m on each side of the river supporting broadly equivalent levels of biodiversity to logged forest. However, width responses varied markedly among taxa, and buffers often lacked forest-dependent species. Much wider buffers than are currently mandated are needed to safeguard most species. The largest biodiversity gains are achieved by increasing relatively narrow buffers. To provide optimal conservation outcomes in tropical production landscapes we encourage policymakers to prescribe width requirements for key taxa and different landscape contexts.Newton-Ungku Omar Fund (grants 216433953, 537134717) – delivered by the British Council and funded by the UK Department for Business, Energy and Industrial Strategy and the Malaysian Industry-Government Group for High Technology – as well as the UK Natural Environment Research Council (NE/K016407/1, NE/K016261/1; https://lombok.nerc-hmtf.info/). MJS was supported by a Research Leadership Award from the Leverhulme Trust

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer

Summary Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886) we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralising antibody titres (NAbT) using a live virus microneutralization assay against wild-type (WT), Delta, Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titres and T cell responses after the fourth vaccine dose increases compared to those after the third vaccine dose. Patients who received B cell-depleting therapies within 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination

Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer

Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities

Peer reviewe

Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 x 10(-8)) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.Peer reviewe