The effects of interactions between proline and carbon nanostructures on organocatalysis in the Hajos-Parrish-Eder-Sauer-Wiechert reaction

The non-covalent interactions of S-(-)-proline with the surfaces of carbon nanostructures (fullerene, nanotubes and graphite) change the nucleophilic-electrophilic and acid-base properties of the amino acid, thus tuning its activity and selectivity in the organocatalytic Hajos-Parrish-Eder-Sauer-Wiechert (HPESW) reaction. Whilst our spectroscopy and microscopy measurements show no permanent covalent bonding between S-(-)-proline and carbon nanostructures, a systematic investigation of the catalytic activity and selectivity of the organocatalyst in the HPESW reaction demonstrates a clear correlation between the pyramidalisation angle of carbon nanostructures and the catalytic properties of S-(-)-proline. Carbon nanostructures with larger pyramidalisation angles have a stronger interaction with the nitrogen atom lone pair of electrons of the organocatalyst, thereby simultaneously decreasing the nucleophilicity and increasing the acidity of the organocatalyst. These translate into lower conversion rates but higher selectivities towards the dehydrated product of Aldol addition

The long-term health and wellbeing impacts of Healthy New Towns: a six-month feasibility study of Healthy New Town demonstrator sites in England

BACKGROUND: Major public health challenges in England include high levels of health risk behaviour and associated diseases. In the context of an ageing population and falls in spending on adult social care, these challenges place huge pressure on health services. There is evidence to show that living environments can shape health, wellbeing and behaviour. However, there is an urgent need to understand how this evidence can be brought together to deliver healthy environments in local urban settings. The HNT programme was commissioned by NHS England in 2015 and is supported by Public Health England. HNTs are 10 major housing developments that aim to improve population health by applying healthy built environment design principles, increasing residents' use of healthy spaces, promoting community activation and cohesion to improve mental health and reduce social isolation, and creating new models for integrating health and social care. The programme provides a natural experiment in which to investigate the effects on health, wellbeing and inequalities of large-scale interventions targeting the wider social determinants of health. RESEARCH QUESTIONS: 1. What are the similarities and differences in the Healthy New Town (HNT) programme developments, activities and processes, contexts and expected impacts and outcomes across the HNT sites? 2. How feasible is the use of existing HNT evaluation data and data from routine sources as the baseline for a longer-term study to assess impact on health, wellbeing and behavioural outcomes, programme processes and mechanisms and Social Return on Investment? AIMS AND OBJECTIVES: 1) To produce participatory systems maps for 5 HNT sites, illustrating processes and expected outcomes from HNT activities and developing a theoretical framework for longer-term research. 2) To scope and synthesise available qualitative data produced through existing local evaluations and to test the feasibility of using this data to ground a longer-term qualitative study of HNT processes. 3) To define primary and secondary outcome measures for assessment of HNT effectiveness and Social Return on Investment, using existing HNT datasets and routinely available data. 4) To test the feasibility of expanding the research programme to include the 5 HNT sites that are not currently in the HNT Evaluation Collaborative to improve study power and representativeness. METHODS The proposed research involves workstreams to: a) use participatory systems mapping with stakeholders in each HNT to produce a theoretical framework for a longer term study on the HNT programme; b) scope and synthesise existing qualitative data from local HNT evaluations to understand local processes and intervention mechanisms; c) scope and standardise local and routinely available data to establish a baseline and feasibility for a longer term study of health and economic outcomes; d) build relationships and recruit 5 further HNTs into the proposed research. TIMELINE FOR DELIVERY The proposed research will be conducted between 1st November 2018 and 30th April 2019 to enable completion while HNT site leads are still in post. ANTICIPATED IMPACT AND DISSEMINATION The proposed research will produce a theoretical framework for the HNT programme, designed to guide further research on the health impacts of HNTs. Findings will be disseminated through peer-reviewed publications and presentations and local audiences including residents, local government and Public Health England

Translocal imagination of Hong Kong connections: the shifting of Chow Yun-Fat's star image since 1997

Anyone who is interested in Hong Kong cinema must be familiar with one name: Chow Yun-fat (b. 1955). He rose to film stardom in the 1980s when Hong Kong cinema started to attract global attention beyond East Asia. During his early screen career, Chow established a star image as an urban citizen of modern Hong Kong through films such as A Better Tomorrow/Yingxiong bense (John Woo, 1986), City on Fire/Longhu fengyun (Ringo Lam, 1987), All About Ah-Long/A Lang de gushi (Johnnie To, 1989), God of Gamblers/Du shen (Wong Jing, 1989), and Hard Boiled/Lashou shentan (John Woo, 1992)

Impaired mucosal defense to acute colonic injury in mice lacking cyclooxygenase-1 or cyclooxygenase-2

To investigate roles in intestinal inflammation for the 2 cyclooxygenase (COX) isoforms, we determined susceptibility to spontaneous and induced acute colitis in mice lacking either the COX-1 or COX-2 isoform. We treated wild-type, COX-1–/–, COX-2–/–, and heterozygous mice with dextran sodium sulfate (DSS) to provoke acute colonic inflammation, and we quantified tissue damage, prostaglandin (PG) E2, and interleukin-1β. No spontaneous gastrointestinal inflammation was detected in mice homozygous for either mutation, despite almost undetectable basal intestinal PGE2 production in COX-1–/– mice. Both COX-1–/– and COX-2–/– mice showed increased susceptibility to a low-dose of DSS that caused mild colonic epithelial injury in wild-type mice. COX-2–/– mice were more susceptible than COX-1–/– mice, and selective pharmacologic blockade of COX-2 potentiated injury in COX-1–/– mice. At a high dose, DSS treatment was fatal to 50% of the animals in each mutant group, but all wild-type mice survived. DSS treatment increased PGE2 intestinal secretion in all groups except COX-2–/– mice. These results demonstrate that COX-1 and COX-2 share a crucial role in the defense of the intestinal mucosa (with inducible COX-2 being perhaps more active during inflammation) and that neither isoform is essential in maintaining mucosal homeostasis in the absence of injurious stimuli

Perceptions of asthma and exercise in adolescents with and without asthma

Objective: To elicit the views of adolescents, with and without asthma, about exercise and asthma, and the perceived benefits of and barriers to participation. The adolescent views elicited would subsequently inform the design of a high-intensity exercise intervention to improve asthma control. Methods: Fifty-four adolescents (age 13.1±0.9years; 26 with asthma) participated in twelve semi-structured group interviews. Questions were structured around knowledge, attitudes and beliefs towards asthma and its impact on exercise participation and lifestyle. The interviews were transcribed verbatim, thematically analysed and presented via diagrams of emergent themes. Ethical approval was granted by the institutional research ethics committee. Results: Fear of an asthma attack emerged as the main barrier to exercise, with many adolescents with asthma withdrawing from exercise as a coping strategy; many healthy adolescents perceived this withdrawal as laziness or an excuse. Despite this, the majority (81%) of adolescents with asthma reported exercise to be their most enjoyable activity. Adolescents suggested incorporating mixed activities, such as team games (e.g., rounders, football, netball), for future interventions to ensure adherence. Conclusions: Whilst exercise is important in the management of asthma, the tendency of those with asthma to withdraw from exercise to avoid adverse events could be addressed through a games-based high-intensity exercise intervention. Furthermore, educating all adolescents on asthma could simultaneously reduce stigmatisation and enhance exercise engagement

Variants of OTOF and PJVK Genes in Chinese Patients with Auditory Neuropathy Spectrum Disorder

BACKGROUND: Mutations in OTOF and PJVK genes cause DFNB9 and DFNB59 types of hearing loss, respectively. The patients carrying pathogenic mutations in either of these genes may show the typical phenotype of auditory neuropathy spectrum disorder (ANSD). The aim of the present study was to identify OTOF and PJVK mutations in sporadic ANSD patients. METHODS AND FINDINGS: A total of 76 unrelated Chinese non-syndromic ANSD patients were sequenced on the gene OTOF and PJVK exon by exon. Variants were valued in 105 controls with normal hearing to verify the carrying rate. We identified one pathogenic mutation (c.1194T>A) and three novel, possibly pathogenic, variants (c.3570+2T>C, c.4023+1 G>A, and c.1102G>A) in the OTOF gene, and one novel, possibly pathogenic, variant (c.548G>A) in PJVK. Moreover, we found three novel missense mutations within the exons of OTOF. CONCLUSIONS: As we identified 4 and 1 possible pathogenic variants of the OTOF gene and the PJVK gene, respectively, we believe that screening in these genes are important in sporadic ANSD patients. The pathogenicity of these novel mutations needs further study because of their single heterozygous nature. Knowledge on the mutation spectra of these genes in Chinese would be beneficial in understanding the genetic character of this worldwide disease

A retrospective study of cochlear implant outcomes in children with residual hearing

BACKGROUND: There has been increasing demand for the cochlear implantation of children who demonstrate some auditory capacity with conventional hearing aids. The purpose of this study was to examine speech recognition outcomes in a group of children who were regarded as borderline candidates for cochlear implantation as their residual hearing and/or auditory functioning levels exceeded typical audiologic candidacy criteria. METHODS: A retrospective chart review was undertaken at one Canadian cochlear implant centre to identify children implanted at age 4 or older with a pure-tone-average of 90 dB or better and speech recognition of 30% or greater. Pre-implant and post-implant open-set word and sentence test scores were analyzed. RESULTS: Eleven children of 195 paediatric cochlear implant recipients met the inclusion criteria for this study. Speech recognition results for the10 English-speaking children indicated significant gains in both open-set word and sentence understanding within the first 6 to 12 months of implant use. Seven of 9 children achieved 80% open-set sentence recognition within 12 months post-surgery. CONCLUSION: Children with several years of experience using conventional amplification demonstrated rapid progress in auditory skills following cochlear implantation. These findings suggest that cochlear implantation may be an appropriate intervention for selected children with severe hearing losses and/or auditory capacity outside current candidacy criteria

Re-inventing artisanal knowledge and practice: a critical review of innovation in a craft-based industry

This paper presents a critical review of the ways in which the specialised knowledge and working practices of craft-based industries have been transformed in the context of broader processes of industrialisation and global competition. The opening section makes the case for artisanal knowledge as a ‘Cinderella’ subject that remains important yet largely uncharted territory for innovation researchers. It is followed by a critical review of existing empirical and theoretical studies that have examined the reproduction and reinvention of artisanal knowledge. The review concludes that valuable insights remain obscured due to the way in which this literature is distributed across discrete disciplines with little evidence of cross-fertilisation or integration. Several common themes emerge, which provide the basis for an outline theoretical framework. The central arguments are illustrated with reference to a case-based analysis of the technological and social innovations that have taken place in English farmhouse cheesemaking over an extended period, from the pre-industrial era to the beginning of the present century. The concluding section considers how more nuanced understandings of artisanal knowledge and practice might enhance innovation theory and contribute to the continued flourishing of craft-based industries

Nanoscale engineering of hybrid magnetite–carbon nanofibre materials for magnetic resonance imaging contrast agents

Magnetic nanomaterials show significant promise as contrast agents for magnetic resonance imaging (MRI). We have developed a new highly efficient one-step procedure for the synthesis of magnetically- functionalised hollow carbon nanofibres, where (i) the carbon nanofibres act as both a template and a support for the nucleation and growth of magnetite nanoparticles and (ii) the structural (size, dispersity and morphology) and functional (magnetisation and coercivity) properties of the magnetic nanoparticles formed on nanofibres are strictly controlled by the mass ratio of the magnetite precursor to the nanofibres and the solvent employed during synthesis. We have shown that our magnetite-nanofibre materials are effectively solubilised in water resulting in a stable suspension that has been employed as a ‘‘negative’’ MRI contrast agent with an excellent transverse relaxivity (r2) of (268 13) mM s 1, surpassing current commercial materials and state-of-the-art magnetic nanoscale platforms in performance for MRI contrast at high magnetic fields. The preparation and evaluation of this unique hybrid nanomaterial represents a critical step towards the realisation of a highly efficient ‘‘smart’’ MRI theranostic agent – a material that allows for the combined diagnosis (with MRI), treatment (with magnetic targeting) and follow-up of a disease (with MRI) – currently in high demand for various clinical applications, including stratified nanomedicine