Evaluation of a multidisciplinary adult integrated respiratory service in the UK.

Rationale, aims and objectives: Care integration, particularly for patients with long-term chronic conditions has been viewed as a key imperative for service improvement over the last decade [1]. In common with other industrialised nations, major care providers such as the National Health Service (NHS) in the United Kingdom (UK) have undertaken service evaluation to identify factors for effective integrated care in the context of increasing demand but also cost-constraints. The aim of this paper is to report on an early process evaluation of a newly established Adult Integrated Respiratory Service (AIRS) in three localities in England. Method: Applied qualitative methods using semi-structured interviews with clinical practitioners (n=19) plus focus group with service users (n=5). University research ethics approval was secured. Findings: Despite finding staff commitment and enthusiasm for a new regional approach, as well as a very positive acclaim from service users, the study highlighted personal and organisational issues and concerns during the first four months of service implementation. The analysis revealed four inter-related themes: service in transition; resistance to change; communication; and challenges to integrated working. The findings support conceptual and organisational elements of integrated care described elsewhere [2, 3]. The role of leadership and change management in the successful implementation of integrated care is explored. Conclusions: The findings from a regional adult integrated respiratory service evaluation in England highlights the potential of collective leadership with authentic involvement of all stakeholders to effect successful change to build locally owned models for integrated care. Further longitudinal research would yield valuable insights as the service evolves

Dorset Adult Integrated Care Service (DAIRS): Service Evalaution

EXECUTIVE SUMMARY This early process evaluation of the newly established Dorset Adult Integrated Respiratory Service (DAIRS) in three localities in Dorset was conducted by Bournemouth University using a mixed-methods approach. Our evaluation showed staff commitment and enthusiasm for a pan-Dorset approach to respiratory care and a very positive acclaim from service users. Mindful of the fact that DAIRS had been in operation for four months only, the evaluation flags up strengths and issues of concern at the initial stages of service implementation. Discussion of the findings has been linked with current thinking to emerge in the White Paper from NHS Improving Quality around service improvement and change management (Bevan & Fairman, 2014). Given that DAIRS has been commissioned in the first instance for a period of two years, this early evaluation will be valuable for stakeholders to address the issues raised in a timely manner. Recommendations 1. Build upon the high levels of satisfaction to engage service user users more widely in the on-going development of DAIRS. 2. Shared documentation needs to be agreed and implemented as soon as possible, including the DAIRS card. 3. DAIRS should be officially launched with appropriate information for different stakeholders: service users, community staff and non-DAIRS hospital staff. 4. The change process should be actively managed; concerns and challenges expressed by participants should be acknowledged and a supportive environment provided for collaborative problem-solving. 5. Consider selection and use of grass roots ‘change champions’ across the sites and disciplines to facilitate a more inclusive model of organisational change. 6. Further integration between localities should be explored particularly around staff education, as well as to facilitate on-going peer support. 7. New staff would benefit from being supernumerary for their first month and visiting neighbouring DAIRS localities. 8. Inclusion and exclusion criteria need to be revisited to ensure a shared understanding amongst DAIRS staff, particularly around co-morbidities. 9. Information and service provision concerning emotional support for service users and carers needs to be reviewed. 10. The current Single Point of Access System (SPOA) should be reviewed to improve compliance. 11. Information Technology (IT) systems and possibilities for joint DAIRS systems should be explored. 12. Perceived financial inequities need to be addressed in service planning. 13. Our evaluation provides a base-line for future work, a further more comprehensive evaluation after two years of DAIRS operation is needed to inform future funding and service development. Suggested factors to include: • Outcome data • Cross-locality service user involvement (avoiding winter peak time), using systematic PREM questionnaire distribution processes. • Community staff perspectives. • Input from related respiratory services, currently not part of DAIRS. • Investigation of impact of a differing skill mix across localities. • More detailed service user feedback. • Evaluation of staff education (DAIRS and non-DAIRS)

Microsatellite association with seed protein content and flowering time in Nigerian cowpea cultivars

Cowpea microsatellites were evaluated for their potential to be used as markers associated with seed protein content and plant flowering time. Seeds with high and low protein content as well as plants with early and late flowering time were selected from 104 Nigerian cowpea accessions. Fifteen (15) microsatellite primer pairs were tested for amplification of microsatellite sequences using PCR and seven pairs amplified a single-locus. Sequence analysis showed a high level of diversity between the analysed genotypes. Although, none of the microsatellites allowed clustering for protein content, one primer pair, VM68, detected a (AG)12-repeat microsatellite allele, which was present only in plants with late flowering. This microsatellite might possibly be useful as a marker associated with late-flowering time.http://www.academicjournals.org/AJBRnf201

Potential use of phytocystatins in crop improvement, with a particular focus on legumes

Phytocystatins are a well-characterized class of naturally-occurring protease inhibitors that function by preventing the catalysis of papain-like cysteine proteases. The action of cystatins in biotic stress resistance has been intensively studied but relatively little is known about their functions in plant growth and defence responses to abiotic stresses, such as drought. Extreme weather events such as drought and flooding will become more frequent as a result of climate change. The concepts that changes in cellular protein content and composition are required for acclimation to different abiotic stresses and that these adjustments are achieved through regulation of proteolysis are widely accepted. However, the nature and regulation of the protein turnover machinery that underpins essential stress-induced cellular re-structuring remains poorly characterised. Cysteine proteases are intrinsic to the genetic programs that underpin developmental senescence, but their functions in stress-induced senescence are poorly defined. While much remains uncertain regarding the individual cysteine protease targets of endogenous cystatins and their precise functions in the regulation of physiological processes are largely unknown, current evidence suggests that manipulation of cysteine protease activities by engineered cystatin expression might be used for to improve the resilience and quality of crop plants in the face of climate change.This work was funded by FP7-PIRSES-GA-2008-230830 (LEGIM) and PIIF-GA-2011- 299347 (Soylife; K.K.). This work was further funded by the International Foundation of Science (IFS grant C/5151-1), the NRF Thuthuka program (B.J.V.) and the NRF Incentive Funding program for rated researchers (K.K.). The funding received from the Genomic Research Institute, University of Pretoria, is hereby also acknowledged. S.G.V.W. thank the NRF/DST in South Africa for bursaries.http://jxb.oxfordjournals.org2016-06-30hb201

Agroinfiltration contributes to VP1 recombinant protein degradation

There is a growing interest in applying tobacco agroinfiltration for recombinant protein production in a plant based system. However, in such a system, the action of proteases might compromise recombinant protein production. Protease sensitivity of model recombinant foot-and-mouth disease (FMD) virus P1-polyprotein (P1) and VP1 (viral capsid protein 1) as well as E. coli glutathione reductase (GOR) were investigated. Recombinant VP1 was more severely degraded when treated with the serine protease trypsin than when treated with the cysteine protease papain. Cathepsin L- and B-like as well as legumain proteolytic activities were elevated in agroinfiltrated tobacco tissues and recombinant VP1 was degraded when incubated with such a protease-containing tobacco extract. In silico analysis revealed potential protease cleavage sites within the P1, VP1 and GOR sequences. The interaction modelling of the single VP1 protein with the proteases papain and trypsin showed greater proximity to proteolytic active sites compared to modelling with the entire P1-polyprotein fusion complex. Several plant transcripts with differential expression were detected 24 hr post-agroinfiltration when the RNA-seq technology was applied to identify changed protease transcripts using the recently available tobacco draft genome. Three candidate genes were identified coding for proteases which included the Responsive-to-Desiccation-21 (RD21) gene and genes for coding vacuolar processing enzymes 1a (NbVPE1a) and 1b (NbVPE1b). The data demonstrates that the tested recombinant proteins are sensitive to protease action and agroinfiltration induces the expression of potential proteases that can compromise recombinant protein production.The National Research Foundation (NRF) and the Genomics Research Institute (GRI), South Africa as well as NRF incentive funding to Karl Kunert and a NRF bursary to Priyen Pillay.http://www.tandfonline.com/loi/kbie202017-08-31hb2016Plant Scienc

Development and use of microsatellites markers for genetic variantion analysis, in the Namibian germplasm, both within and between populations of marama bean (Tylosema esculentum)

Tylosema esculentum (marama) has long been identified as a candidate crop for arid and semi-arid environments due to its success in these environments and the high nutritional value of the seed. Molecular markers are essential for the assessment of the levels of genetic variation present within and between populations of marama as well for future marker-assisted breeding efforts. Microsatellites were isolated using a modified FIASCO enrichment technique. Eighty pairs of primers were designed to amplify across a selected set of perfect microsatellite repeats with greater than 5 repeat units. Of the 80 primer pairs screened, 76% were able to detect polymorphism and 21% gave monomorphic bands while the other 3% gave inconsistent results. Four of the polymorphic SSR’s were used for genetic variation analysis and have proved to be useful and informative markers for assessing intra-specific and interspecific variability of marama bean. Heterozygosity (H) within and between populations of marama bean in the Namibian germplasm ranged from 0.30 to 0.74. Some of the populations had low genetic variation while others had high genetic variation

Review : The future of cystatin engineering

Plant cystatins are naturally occurring protease inhibitors that prevent proteolysis by papain-like cysteine proteases. Their protective action against environmental stresses has been relatively well characterised. Still, there is a need to greatly improve both potency and specificity based on the current rather poor performance of cystatins in biotechnological applications. Research in creating more potent and specific cystatins, including amino acid substitutions in either conserved cystatin motifs and/or at variable amino acid sites, is reviewed. Existing gaps for better understanding of cystatin-protease interactions are further explored. Current knowledge on multi-cystatins or hybrid protease inhibitors involving cystatins as an additional option for cystatin engineering is further outlined along with the nuances of how cystatins with rather unusual amino acid sequences might actually help in cystatin engineering. Finally, future opportunities for application of cystatins are highlighted which include applications in genetically modified transgenic plants for environmental stress protection and also as nutraceuticals, as part of more nutritious food. Further opportunities might also include the possible management of diseases and disorders, often associated with lifestyle changes, and the most immediate and promising application which is inclusion into plant-based recombinant protein production platforms.International Foundation of Science (IFS grant C/5151-1), the NRF Incentive funding for rated researchers (90779) and the NRF National Bioinformatics Functional Genomics program(86947). Funding received from the Genomic Research Institute (GRI), University of Pretoria.http://www.elsevier.com/locate/plantsci2017-05-31hb2016Forestry and Agricultural Biotechnology Institute (FABI)Plant Production and Soil SciencePlant Scienc

Analytical solutions to zeroth-order dispersion relations of a cylindrical metallic nanowire

Zeroth-order complex dispersion relations of a cylindrical metallic nanowire have been solved out analytically with approximate methods. The analytical solutions are valid for the sections of the dispersion relations whose frequencies are close to the Surface Plasmon frequency. The back bending of the Surface Plasmon-Polaritons(SPPs) can be well described by the analytical solutions, confirming that the back bending is originated from the metal Ohmic loss. The utility of the back bending point in the dispersion relation for the measurement of the metallic Ohimc loss has also been suggested.Comment: 6pages, 3figure

Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.

Evaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia

Schizophrenia genome-wide association studies have identified >150 regions of the genome associated with disease risk, yet there is little evidence that coding mutations contribute to this disorder. To explore the mechanism of non-coding regulatory elements in schizophrenia, we performed ATAC-seq on adult prefrontal cortex brain samples from 135 individuals with schizophrenia and 137 controls, and identified 118,152 ATAC-seq peaks. These accessible chromatin regions in the brain are highly enriched for schizophrenia SNP heritability. Accessible chromatin regions that overlap evolutionarily conserved regions exhibit an even higher heritability enrichment, indicating that sequence conservation can further refine functional risk variants. We identify few differences in chromatin accessibility between cases and controls, in contrast to thousands of age-related differential accessible chromatin regions. Altogether, we characterize chromatin accessibility in the human prefrontal cortex, the effect of schizophrenia and age on chromatin accessibility, and provide evidence that our dataset will allow for fine mapping of risk variants