Synthetic approaches to polyoxygenated chromone and chromanome natural products

The work described in this thesis is concerned with the chemistry ofpolymethoxylated aromatic carbonyl compounds bearing a 2,6-dioxygenatedsubstitution pattern, with particular regard to establishing synthetic routes tobiologically active chromone and chromanone systems. Syntheses of keyintermediates in the approaches to the natural products stigmatellin, baicalein andLL-D253(x (and related products) were undertaken.In chapter one the reactions of nucleophiles at the carbonyl moieties of 2,6-dioxygenated benzene carbonyl compounds are reviewed. This type of processocan present special difficulties and was to prove particularly significant at variousstageso f the work describedi n subsequenct hapters.Chapter two is a review of the provenance, abundance, biosynthesis, and previoussyntheses of the natural products stigmatellin, baicalein and LL-D253(x, thesebeing the targets of the synthetic work undertaken in the course of the project.Chapter three is concerned with an approach to a fragment of the stigmatellinmolecule (referred to as stigmatellin fragment A) using the Vilsmeier formylationreaction, while chapter four is concerned with an alternative approach tostigmatellin fragment A using Friedel-Crafts acylation methodology. Thestrategies and the results obtained are described and analysed in detail.In chapter five a strategy for the synthesis of baicalein trimethyl ether is describedand the results obtained are discussed

Audit of the job satisfaction levels of the UK radiography and physics workforce in UK radiotherapy centres 2012

Conclusion: Radiotherapy professionals are prone to the effects of compassion fatigue and burnout. Attention must be paid to workload and its impact on practitioners' job satisfaction. Professional development that is supported and informed by a performance development review is a simple and effective means of enhancing satisfaction. Individuals have a responsibility to themselves and their colleagues as their behaviours and attitudes influence job satisfaction. Advances in knowledge: This work identifies areas for future research to enhance the professional resilience of practitioners, in order to provide high-quality treatments. Objective: Workforce planning reports identify a staff shortfall that jeopardizes the ability of UK radiotherapy centres to meet future demands. Obtaining an understanding of the work experiences of radiotherapy professionals will support the development of strategies to increase job satisfaction, productivity and effectiveness. Methods: A quantitative survey assessed job satisfaction, attitudes to incident reporting, stress and burnout, opportunities for professional development, workload, retention and turnover. Clinical oncologists were not included, as the Royal College of Radiologists, London, UK, had recently assessed their members' satisfaction. All questions were taken from validated instruments or adapted from the "UK National Health Service Staff Survey". Results: The survey yielded 658 completed responses (approximately 16% response rate), from public and private sectors. Over a third (36%) of respondents were classified as satisfied for job satisfaction with 11% dissatisfied and the remaining 53% ambivalent. A significant proportion of clinical staff (37.5%) report high emotional exhaustion. Presenteeism was an issue with 42.4% attending work despite feeling unable to fulfil their role.</p

Evidence for models of diagnostic service provision in the community: literature mapping exercise and focused rapid reviews

Background Current NHS policy favours the expansion of diagnostic testing services in community and primary care settings. Objectives Our objectives were to identify current models of community diagnostic services in the UK and internationally and to assess the evidence for quality, safety and clinical effectiveness of such services. We were also interested in whether or not there is any evidence to support a broader range of diagnostic tests being provided in the community. Review methods We performed an initial broad literature mapping exercise to assess the quantity and nature of the published research evidence. The results were used to inform selection of three areas for investigation in more detail. We chose to perform focused reviews on logistics of diagnostic modalities in primary care (because the relevant issues differ widely between different types of test); diagnostic ultrasound (a key diagnostic technology affected by developments in equipment); and a diagnostic pathway (assessment of breathlessness) typically delivered wholly or partly in primary care/community settings. Databases and other sources searched, and search dates, were decided individually for each review. Quantitative and qualitative systematic reviews and primary studies of any design were eligible for inclusion. Results We identified seven main models of service that are delivered in primary care/community settings and in most cases with the possible involvement of community/primary care staff. Not all of these models are relevant to all types of diagnostic test. Overall, the evidence base for community- and primary care-based diagnostic services was limited, with very few controlled studies comparing different models of service. We found evidence from different settings that these services can reduce referrals to secondary care and allow more patients to be managed in primary care, but the quality of the research was generally poor. Evidence on the quality (including diagnostic accuracy and appropriateness of test ordering) and safety of such services was mixed. Conclusions In the absence of clear evidence of superior clinical effectiveness and cost-effectiveness, the expansion of community-based services appears to be driven by other factors. These include policies to encourage moving services out of hospitals; the promise of reduced waiting times for diagnosis; the availability of a wider range of suitable tests and/or cheaper, more user-friendly equipment; and the ability of commercial providers to bid for NHS contracts. However, service development also faces a number of barriers, including issues related to staffing, training, governance and quality control. Limitations We have not attempted to cover all types of diagnostic technology in equal depth. Time and staff resources constrained our ability to carry out review processes in duplicate. Research in this field is limited by the difficulty of obtaining, from publicly available sources, up-to-date information about what models of service are commissioned, where and from which providers. Future work There is a need for research to compare the outcomes of different service models using robust study designs. Comparisons of ‘true’ community-based services with secondary care-based open-access services and rapid access clinics would be particularly valuable. There are specific needs for economic evaluations and for studies that incorporate effects on the wider health system. There appears to be no easy way of identifying what services are being commissioned from whom and keeping up with local evaluations of new services, suggesting a need to improve the availability of information in this area. Funding The National Institute for Health Research Health Services and Delivery Research programme

Hormone-sensing cells require Wip1 for paracrine stimulation in normal and premalignant mammary epithelium

10.1186/bcr3381Breast Cancer Research15

Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics

In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective microbiota-mediated mechanisms was retained. Beneficial health effects must be documented for a substance to be considered a prebiotic. The consensus definition applies also to prebiotics for use by animals, in which microbiota-focused strategies to maintain health and prevent disease is as relevant as for humans. Ultimately, the goal of this Consensus Statement is to engender appropriate use of the term ‘prebiotic’ by relevant stakeholders so that consistency and clarity can be achieved in research reports, product marketing and regulatory oversight of the category. To this end, we have reviewed several aspects of prebiotic science including its development, health benefits and legislation

Absence of renal hypoxia in the subacute phase of severe renal ischemia reperfusion injury

 This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this recordTissue hypoxia has been proposed as an important event in renal ischemia reperfusion injury (IRI) particularly during the period of ischemia and in the immediate hours following reperfusion. However, little is known about renal oxygenation during the subacute phase of IRI. We employed four different methods to assess the temporal and spatial changes in tissue oxygenation during the subacute phase (24 h and 5 days after reperfusion) of a severe form of renal IRI in rats. We hypothesized that the kidney is hypoxic 24 h and 5 days after an hour of bilateral renal ischemia, driven by a disturbed balance between renal oxygen delivery (DO2) and oxygen consumption (VO2). Renal DO2 was not significantly reduced in the subacute phase of IRI. In contrast, renal VO2 was 55% less 24 h, and 49% less 5 days after reperfusion than after sham-ischemia. Inner medullary tissue PO2, measured by radiotelemetry was 25 {plus minus} 12% greater 24 h after ischemia than after sham-ischemia. By 5 days after reperfusion, tissue PO2 was similar to that in rats subjected to sham-ischemia. Tissue PO2 measured by Clark electrode was consistently greater 24 h, but not 5 days, after ischemia than after sham-ischemia. Cellular hypoxia, assessed by pimonidazole adduct immunohistochemistry, was largely absent at both time-points and tissue levels of hypoxia inducible factors were downregulated following renal ischemia. Thus, in this model of severe IRI, tissue hypoxia does not appear to be an obligatory event during the subacute phase, likely due to the markedly reduced oxygen consumption.British Heart FoundationBritish Heart FoundationNational Health and Medical Research Council of AustraliaEuropean Union, Seventh Framework Programm

Effects of different culture conditions (photoautotrophic, photomixotrophic) and the auxin indole-butyric acid on the in vitro acclimatization of papaya (Carica papaya L. var. Red Maradol) plants using zeolite as support

Plant regeneration of papaya via organogenesis and somatic embryogenesis has been successful;  however, the biggest problem of in vitro culture of this species is the acclimatization of regenerated  plants, where over 70% of the plants are lost before being planted in the field. Decreasing the relative humidity inside the culture vessel and thus increasing the ventilation, appears to have a greater effect on  the adaptation of papaya plants, strengthening the function of the stomata and with this, allowing better  control of water loss from the leaves. The aim of this study was to determine the effects of different  concentrations of sucrose and indole-butyric acid (IBA) on rooting and in vitro acclimatization of plants  using sterile zeolite as support and culture vessels with increased ventilation. Three concentrations of  sucrose (0, 10 and 20 g L-1) were studied with and without auxin and as the control treatment, the  rooting culture medium with agar during 17, 27 and 37 culture days. The highest percentage of rooting  was recorded at 37 culture days in the treatment without sucrose and IBA with 80.0% and zeolite as  support. The best photosynthetic values were achieved when in vitro shoots were grown in culture  medium with auxin and different concentrations of sucrose, even though they were also high in the  treatment without the presence of IBA and without sucrose at 17 days of culture. The combined effect of the zeolite, auxin (IBA), without sucrose in the culture medium and increased ventilation allowed   photoautotrophic culture conditions which had effect of the increasing plant survival under ex vitro  acclimatization conditions.Key words: Carica papaya, photosynthesis, roots formation

Shade alters savanna grass layer structure and function along a gradient of canopy cover

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordData availability statement: Data used for this study are available as supporting information.Aim: In savannas, a grass-dominated ground layer is key to ecosystem function via grass–fire feedbacks that maintain open ecosystems. With woody encroachment, tree density increases, thereby decreasing light in the ground layer and potentially altering ecosystem function. We investigated how light availability can filter individual grass species distributions and whether different functional traits are associated with response to a shade gradient in a landscape experiencing woody encroachment. Location: Savanna–forest mosaic in the Cerrado domain, southeastern Brazil. Methods: Along an encroachment gradient of increasing tree leaf area index (LAI) and shade, we determined how changing light availability alters grass diversity and ground layer structure relative to grass cover and grass functional traits (photosynthetic pathway, underground storage organs, bud protection and traits related to grass shape, size and leaf dimensions). Results: Increasing shade led to a decrease in grass cover and grass species richness, and also compositional and functional changes. We found that where tree LAI reached 1, grass cover was reduced by 50% and species richness by 30%. While C4 grass species abundances decreased with increasing shade, the opposite pattern was true for C3 grasses. There were only small differences in light preferences among C4 subtypes, with phosphoenolpyruvate carboxykinase (PCK) species tolerating slightly more shaded conditions. Persistence of some C4 species under more shaded conditions was possible, likely due to an ability to store starch reserves via underground storage organs. Conclusions: Woody encroachment changes diversity and structure of the grassy layer that is critical to the functioning of savanna ecosystems, highlighting the dependence of the diverse grass layer on open and sunny conditions. Our results suggest a threshold of tree cover close to LAI ≈ 1 as being critical to cerrado grassy layer conservation.National Science Foundation (NSF)São Paulo Research Foundation (FAPESP)National Council for Scientific and Technological DevelopmentCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES