Recent trends in UK insects that inhabit early successional stages of ecosystems

Improved recording of less popular groups, combined with new statistical approaches that compensate for datasets that were hitherto too patchy for quantitative analysis, now make it possible to compare recent trends in the status of UK invertebrates other than butterflies. Using BRC datasets, we analysed changes in status between 1992 and 2012 for those invertebrates whose young stages exploit early seral stages within woodland, lowland heath and semi-natural grassland ecosystems, a habitat type that had declined during the 3 decades previous to 1990 alongside a disproportionally high number of Red Data Book species that were dependent on it. Two clear patterns emerged from a meta-analysis involving 299 classifiable species belonging to ten invertebrate taxa: (i) during the past 2 decades, most early seral species that are living near their northern climatic limits in the UK have increased relative to the more widespread members of these guilds whose distributions were not governed by a need for a warm micro-climate; and (ii) independent of climatic constraints, species that are restricted to the early stages of woodland regeneration have fared considerably less well than those breeding in the early seral stages of grasslands or, especially, heathland. The first trend is consistent with predicted benefits for northern edge-of-range species as a result of climate warming in recent decades. The second is consistent with our new assessment of the availability of early successional stages in these three ecosystems since c. 1990. Whereas the proportion and continuity of early seral patches has greatly increased within most semi-natural grasslands and lowland heaths, thanks respectively to agri-environmental schemes and conservation management, the representation of fresh clearings has continued to dwindle within UK woodlands, whose floors are increasingly shaded and ill-suited for this important guild of invertebrates

Development and evaluation of a high-throughput, low-cost genotyping platform based on oligonucleotide microarrays in rice

<p>Abstract</p> <p>Background</p> <p>We report the development of a microarray platform for rapid and cost-effective genetic mapping, and its evaluation using rice as a model. In contrast to methods employing whole-genome tiling microarrays for genotyping, our method is based on low-cost spotted microarray production, focusing only on known polymorphic features.</p> <p>Results</p> <p>We have produced a genotyping microarray for rice, comprising 880 single feature polymorphism (SFP) elements derived from insertions/deletions identified by aligning genomic sequences of the <it>japonica </it>cultivar Nipponbare and the <it>indica </it>cultivar 93-11. The SFPs were experimentally verified by hybridization with labeled genomic DNA prepared from the two cultivars. Using the genotyping microarrays, we found high levels of polymorphism across diverse rice accessions, and were able to classify all five subpopulations of rice with high bootstrap support. The microarrays were used for mapping of a gene conferring resistance to <it>Magnaporthe grisea</it>, the causative organism of rice blast disease, by quantitative genotyping of samples from a recombinant inbred line population pooled by phenotype.</p> <p>Conclusion</p> <p>We anticipate this microarray-based genotyping platform, based on its low cost-per-sample, to be particularly useful in applications requiring whole-genome molecular marker coverage across large numbers of individuals.</p

Leukemic blasts program bone marrow adipocytes to generate a protumoral microenvironment

Despite currently available therapies most patients diagnosed with acute myeloid leukemia (AML) die of their disease. Tumor-host interactions are critical for the survival and proliferation of cancer cells; accordingly, we hypothesise that specific targeting of the tumor microenvironment may constitute an alternative or additional strategy to conventional tumor-directed chemotherapy. Since adipocytes have been shown to promote breast and prostate cancer proliferation, and because the bone marrow adipose tissue (MAT) accounts for up to 70% of bone marrow volume in adult humans, we examined the adipocyte-leukaemia cell interactions to determine if they are essential for the growth and survival of AML. Using in-vivo and in-vitro models of AML we show that bone marrow adipocytes from the tumor microenvironment support the survival and proliferation of malignant cells from patients with AML. We show that AML blasts alter metabolic processes in adipocytes to induce phosphorylation of hormone-sensitive lipase and consequently activate lipolysis, which then enables the transfer of fatty acids from adipocytes to AML blasts. In addition, we report that fatty acid binding protein-4 (FABP4) mRNA is up-regulated in adipocytes and AML when in co-culture. FABP4 inhibition using FABP4 shRNA knockdown or a small molecule inhibitor prevents AML proliferation on adipocytes. Moreover, knockdown of FABP4 increases survival in Hoxa9/Meis1-driven AML model. Finally, knockdown of carnitine palmitoyltransferase IA (CPT1A) in an AML patient-derived xenograft model improves survival. Here we report the first description of AML programming bone marrow adipocytes to generate a pro-tumoral microenvironment

Covalent immobilisation of antibodies in Teflon-FEP microfluidic devices for sensitive quantification of clinically relevant protein biomarkers

This study reports for the first time sensitive colorimetric and fluorescence detection of clinically relevant protein biomarkers by sandwich immunoassays using covalent immobilisation of antibodies onto the fluoropolymer surface inside Teflon®-FEP microfluidic devices. Teflon®-FEP has outstanding optical transparency ideal for high-sensitivity colorimetric and fluorescence bioassays, however this thermoplastic is regarded as chemically inert and very hydrophobic. Covalent immobilisation can offer benefits over passive adsorption to plastic surfaces by allowing better control over antibody density, orientation and analyte binding capacity, and so we tested a range of different and novel covalent immobilisation strategies. We first functionalised the inner surface of a 10-bore, 200 µm internal diameter FEP microcapillary film with high-molecular weight polyvinyl alcohol (PVOH) without changing the outstanding optical transparency of the device delivered by the matched refractive index of FEP and water. Glutaraldehyde immobilisation was compared with use of photoactivated linkers and NHS-ester crosslinkers for covalently immobilising capture antibodies onto PVOH. Three clinically relevant sandwich ELISAs were tested, against the cytokine IL-1ß, the myocardial infarct marker cardiac troponin I (cTnI), and the chronic heart failure marker brain natriuretic peptide (BNP). Overall, glutaraldehyde immobilisation was effective for BNP assays, but yielded unacceptable background for IL-1ß and cTnI assays caused by direct binding of biotinylated detection antibody to the modified PVOH surface. We found NHS-ester groups reacted with APTES-treated PVOH coated fluoropolymer. This facilitated a novel method for capture antibody immobilisation onto fluoropolymer devices using a bifunctional NHS-maleimide crosslinker. The density of covalently immobilised capture antibodies achieved using PVOH/APTES/NHS/Maleimide approached levels seen with passive adsorption, and sensitive and quantitative assay performance was achieved using this method. Overall, PVOH coating provided an excellent surface for controlled covalent antibody immobilisation onto Teflon®-FEP for performing high-sensitivity immunoassays

Lab on a stick: multi-analyte cellular assays in a microfluidic dipstick

A new microfluidic concept for multi-analyte testing in a dipstick format is presented, termed “Lab-on-a-Stick”, that combines the simplicity of dipstick tests with the high performance of microfluidic devices. Lab-on-a-Stick tests are ideally suited to analysis of particulate samples such as mammalian or bacterial cells, and capable of performing multiple different parallel microfluidic assays when dipped into a single sample with results recorded optically. The utility of this new diagnostics format was demonstrated by performing three types of multiplex cellular assays that are challenging to perform in conventional dipsticks: 1) instantaneous ABO blood typing; 2) microbial identification; and 3) antibiotic minimum inhibitory (MIC) concentration measurement. A pressure balance model closely predicted the superficial flow velocities in individual capillaries, that were overestimated by up to one order of magnitude by the Lucas-Washburn equation conventionally used for wicking in cylindrical pores. Lab-on-a-stick provides a cost-effective, simple, portable and flexible multiplex platform for a range of assays, and will deliver a new generation of advanced yet affordable point-of-care tests for global diagnostics

Ethical issues in implementation research: a discussion of the problems in achieving informed consent

Background: Improved quality of care is a policy objective of health care systems around the world. Implementation research is the scientific study of methods to promote the systematic uptake of clinical research findings into routine clinical practice, and hence to reduce inappropriate care. It includes the study of influences on healthcare professionals' behaviour and methods to enable them to use research findings more effectively. Cluster randomized trials represent the optimal design for evaluating the effectiveness of implementation strategies. Various codes of medical ethics, such as the Nuremberg Code and the Declaration of Helsinki inform medical research, but their relevance to cluster randomised trials in implementation research is unclear. This paper discusses the applicability of various ethical codes to obtaining consent in cluster trials in implementation research. Discussion: The appropriate application of biomedical codes to implementation research is not obvious. Discussion of the nature and practice of informed consent in implementation research cluster trials must consider the levels at which consent can be sought, and for what purpose it can be sought. The level at which an intervention is delivered can render the idea of patient level consent meaningless. Careful consideration of the ownership of information, and rights of access to and exploitation of data is required. For health care professionals and organizations, there is a balance between clinical freedom and responsibility to participate in research. Summary: While ethical justification for clinical trials relies heavily on individual consent, for implementation research aspects of distributive justice, economics, and political philosophy underlie the debate. Societies may need to trade off decisions on the choice between individualized consent and valid implementation research. We suggest that social sciences codes could usefully inform the consideration of implementation research by members of Research Ethics Committees

Developing diversity through specialisation in secondary education: comparing approaches in New Zealand and England

The paper compares approaches to curriculum specialisation in secondary education in New Zealand and England. In both countries there have been movements towards increased specialisation, though these have been quite different in form and scope. In both countries specialisation cannot be divorced from broader education policies designed to increase devolution and choice and the paper discusses these contexts before analysing the different approaches to specialisation and attempting an explanation. The authors of the paper draw on findings from research undertaken in New Zealand schools. The paper identifies three dimensions that have played a part in influencing curriculum specialisation in both countries. These are opportunity, source of impetus and support. It is argued that while local initiative is possible in New Zealand, central planning and guidance is inadequate. In England while central planning is strong and support is available, it is far from clear that real specialisation is encouraged by existing curriculum and assessment frameworks. In these circumstances in both countries it seems likely that vertical, rather than horizontal, diversity will continue to hold sway

Emergency department clinical leads’ experiences of implementing primary care services where GPs work in or alongside emergency departments in the UK: a qualitative study

Background To manage increasing demand for emergency and unscheduled care NHS England policy has promoted services in which patients presenting to Emergency Departments (EDs) with non-urgent problems are directed to general practitioners (GPs) and other primary care clinicians working within or alongside emergency departments. However, the ways that hospitals have implemented primary care services in EDs are varied. The aim of this study was to describe ED clinical leads’ experiences of implementing and delivering ‘primary care services’ and ‘emergency medicine services’ where GPs were integrated into the ED team. Methods We conducted interviews with ED clinical leads in England (n = 19) and Wales (n = 2). We used framework analysis to analyse interview transcripts and explore differences across ‘primary care services’, ‘emergency medicine services’ and emergency departments without primary care services. Results In EDs with separate primary care services, success was reported when having a distinct workforce of primary care clinicians, who improved waiting times and flow by seeing primary care-type patients in a timely way, using fewer investigations, and enabling ED doctors to focus on more acutely unwell patients. Some challenges were: trying to align their service with the policy guidance, inconsistent demand for primary care, accessible community primary care services, difficulties in recruiting GPs, lack of funding, difficulties in agreeing governance protocols and establishing effective streaming pathways. Where GPs were integrated into an ED workforce success was reported as managing the demand for both emergency and primary care and reducing admissions. Conclusions Introducing a policy advocating a preferred model of service to address primary care demand was not useful for all emergency departments. To support successful and sustainable primary care services in or alongside EDs, policy makers and commissioners should consider varied ways that GPs can be employed to manage variation in local demand and also local contextual factors such as the ability to recruit and retain GPs, sustainable funding, clear governance frameworks, training, support and guidance for all staff. Whether or not streaming to a separate primary care service is useful also depended on the level of primary care demand