Wnt4 antagonises Wnt3a mediated increases in growth and glucose stimulated insulin secretion in the pancreatic beta-cell line, INS-1

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.The Wnt signalling pathway in beta-cells has been linked to the development of type 2 diabetes. Investigating the impact of a non-canonical Wnt ligand, Wnt4, on beta-cell function we found that in INS-1 cells, Wnt4 was able to completely block Wnt3a stimulated cell growth and insulin secretion. However, despite high levels of Wnt4 protein being detected in INS-1 cells, reducing the expression of Wnt4 had no impact on cell growth or Wnt3a signalling. As such, the role of the endogenously expressed Wnt4 in beta-cells is unclear, but the data showing that Wnt4 can act as a negative regulator of canonical Wnt signalling in beta-cells suggests that this pathway could be a potential target for modulating beta-cell function.This work was supported by the Northcott Devon Medical Foundation (grant TB/MG/NO5002/141109 to HJW)

Survey of ultrasound practice amongst podiatrists in the UK

Background: Ultrasound in podiatry practice encompasses musculoskeletal ultrasound imaging, vascular hand-held Doppler ultrasound and therapeutic ultrasound. Sonography practice is not regulated by the Health and Care Professions Council (HCPC), with no requirement to hold a formal qualification. The College of Podiatry does not currently define ultrasound training and competencies. This study aimed to determine the current use of ultrasound, training received and mentorship received and/or provided by podiatrists using ultrasound. Methods: A quantitative study utilising a cross-sectional, on-line, single-event survey was undertaken within the UK. Results: Completed surveys were received from 284 podiatrists; 173 (70%) use ultrasound as part of their general practice, 139 (49%) for musculoskeletal problems, 131 (46%) for vascular assessment and 39 (14%) to support their surgical practice. Almost a quarter (n=62) worked for more than one organisation; 202 (71%) were employed by the NHS and/or private sector (n=118, 41%). Nearly all (93%) respondents report using a hand-held vascular Doppler in their daily practice; 216 (82%) to support decisions regarding treatment options, 102 (39%) to provide diagnostic reports for other health professionals, and 34 (13%) to guide nerve blocks. Ultrasound imaging was used by 104 (37%) respondents primarily to aid clinical decision making (n=81) and guide interventions (steroid injections n=67; nerve blocks n=39). Ninety-three percent stated they use ultrasound imaging to treat their own patients, while others scan at the request of other podiatrists (n=28) or health professionals (n=18). Few use ultrasound imaging for research (n=7) or education (n=2). Only 32 (11%) respondents (n=20 private sector) use therapeutic ultrasound to treat patients presenting with musculoskeletal complaints, namely tendon pathologies. Few respondents (18%) had completed formal post-graduate CASE (Consortium for the Accreditation of Sonographic Education) accredited ultrasound courses. Forty (14%) respondents receive ultrasound mentorship; the majority from fellow podiatrists (n=17) or medical colleagues (n=15). Over half (n=127) who do not have ultrasound mentorship indicated they would like a mentor predominantly for ultrasound imaging. Fifty-five (19%) report they currently provide ultrasound mentorship for others. Conclusions: Understanding the scope of ultrasound practice, the training undertaken and the requirements for mentorship will underpin the development of competencies and recommendations defined by the College of Podiatry to support professional development and ensure safe practice.</p

Adoption of precision livestock farming technologies has the potential to mitigate greenhouse gas emissions from beef production

To meet the objectives of the Paris Agreement, which aims to limit the increase in global temperature to 1.5°C, significant greenhouse gas (GHG) emission reductions will be needed across all sectors. This includes agriculture which accounts for a significant proportion of global GHG emissions. There is therefore a pressing need for the uptake of new technologies on farms to reduce GHG emissions and move towards current policy targets. Recently, precision livestock farming (PLF) technologies have been highlighted as a promising GHG mitigation strategy to indirectly reduce GHG emissions through increasing production efficiencies. Using Scotland as a case study, average data from the Scottish Cattle Tracing System (CTS) was used to create two baseline beef production scenarios (one grazing and one housed system) and emission estimates were calculated using the Agrecalc carbon footprinting tool. The effects of adopting various PLF technologies on whole farm and product emissions were then modelled. Scenarios included adoption of automatic weigh platforms, accelerometer based sensors for oestrus detection (fertility sensors) and accelerometer-based sensors for early disease detection (health sensors). Model assumptions were based on validated technologies, direct experience from farms and expert opinion. Adoption of all three PLF technologies reduced total emissions (kgCO2e) and product emissions (kg CO2e/kg deadweight) in both the grazing and housed systems. In general, adoption of PLF technologies had a larger impact in the housed system than in the grazing system. For example, while health sensors reduced total emissions by 6.1% in the housed system, their impact was slightly lower in the grazing system at 4.4%. The largest reduction in total emissions was seen following the adoption of an automatic weight platform which reduced the age at slaughter by 3  months in the grazing system (6.8%) and sensors for health monitoring in the housed system (6.1%). Health sensors also resulted in the largest reduction in product emissions for both the housed (12.0%) and grazing systems (10.5%). These findings suggest PLF could be an effective GHG mitigation strategy for beef systems in Scotland. Although this study utilised data from beef farms in Scotland, comparable emission reductions are likely attainable in other European countries with similar farming systems

Adoption of precision livestock farming technologies has the potential to mitigate greenhouse gas emissions from beef production

To meet the objectives of the Paris Agreement, which aims to limit the increase in global temperature to 1.5°C, significant greenhouse gas (GHG) emission reductions will be needed across all sectors. This includes agriculture which accounts for a significant proportion of global GHG emissions. There is therefore a pressing need for the uptake of new technologies on farms to reduce GHG emissions and move towards current policy targets. Recently, precision livestock farming (PLF) technologies have been highlighted as a promising GHG mitigation strategy to indirectly reduce GHG emissions through increasing production efficiencies. Using Scotland as a case study, average data from the Scottish Cattle Tracing System (CTS) was used to create two baseline beef production scenarios (one grazing and one housed system) and emission estimates were calculated using the Agrecalc carbon footprinting tool. The effects of adopting various PLF technologies on whole farm and product emissions were then modelled. Scenarios included adoption of automatic weigh platforms, accelerometer based sensors for oestrus detection (fertility sensors) and accelerometer-based sensors for early disease detection (health sensors). Model assumptions were based on validated technologies, direct experience from farms and expert opinion. Adoption of all three PLF technologies reduced total emissions (kgCO2e) and product emissions (kg CO2e/kg deadweight) in both the grazing and housed systems. In general, adoption of PLF technologies had a larger impact in the housed system than in the grazing system. For example, while health sensors reduced total emissions by 6.1% in the housed system, their impact was slightly lower in the grazing system at 4.4%. The largest reduction in total emissions was seen following the adoption of an automatic weight platform which reduced the age at slaughter by 3  months in the grazing system (6.8%) and sensors for health monitoring in the housed system (6.1%). Health sensors also resulted in the largest reduction in product emissions for both the housed (12.0%) and grazing systems (10.5%). These findings suggest PLF could be an effective GHG mitigation strategy for beef systems in Scotland. Although this study utilised data from beef farms in Scotland, comparable emission reductions are likely attainable in other European countries with similar farming systems

The impacts of precision livestock farming tools on the greenhouse gas emissions of an average Scottish dairy farm

Precision livestock farming (PLF) tools are increasingly used in daily herd management to improve health, welfare, and overall production. While not intended to reduce greenhouse gas (GHG) emissions on farm, PLF tools can do so indirectly by improving overall efficiency, thereby reducing the emissions per unit of product. This work modelled the potential effects of commercially available PLF tools on whole enterprise and product emissions of two average Scottish dairy farm systems (an 8,000  L and 10,000  L herd) using the Agrecalc carbon foot printing tool. Scenarios modelled included an improvement infertility and an improvement in fertility and yield from the introduction of an accelerometer-based sensor, and an improvement in health from introduction of an accelerometer-based sensor, with and without the use of management interventions. Use of a sensor intended to improve fertility had the large streduction in total emissions (kg CO2e) of −1.42% for a 10,000  L farm, with management changes applied. The largest reduction in emissions from milk production (kg CO2e) of −2.31% was observed via fertility technology application in an 8,000  L farm, without management changes. The largest reduction in kg CO2e per kg fat and protein corrected milk of −6.72% was observed from an improvement in fertility and yield in a 10,000  L herd, with management changes. This study has highlighted the realistic opportunities available to dairy farmers in low and high input dairy systems to reduce their emissions through adoption of animal mounted PLF technologies

Training the next generation of clinical researchers: Evaluation of a graduate podiatrist research internship in rheumatology

Background: The aim of this study was to evaluate the effectiveness of the Arthritis Research UK funded graduate internship scheme for podiatrists and to explore the experiences of interns and mentors. Methods: Nine new graduates completed the internship programme (July 2006-June 2010); six interns and two mentors participated in this study. The study was conducted in three phases. Phase 1: quantitative survey of career and research outcomes for interns. Phase 2 and 3: qualitative asynchronous interviews through email to explore the experiences of interns and mentors. Interpretive phenomenological analysis (IPA) of coded transcripts identified recurring themes. Results: Research outputs included ten peer reviewed publications with authorial contributions from interns, 23 conference abstract presentations and one subsequent 'Jewel in the Crown' award at the British Society for Rheumatology Conference. Career progression includes two National Institute for Health research (NIHR) PhD fellowships, two Arthritis Research UK PhD fellowships, one NIHR Master of Research fellowship and one specialist rheumatology clinical post. Two interns are members of NIHR and professional body committees. Seven important themes arose from the qualitative phases: perceptions of the internship pre-application; internship values; maximising personal and professional development; psychosocial components of the internship; the role of mentoring and networking; access to research career pathways; perceptions of future developments for the internship programme. The role of mentorship and the peer support network have had benefits that have persisted beyond the formal period of the scheme. Conclusions: The internship model appears to have been perceived to have been valuable to the interns' careers and may have contributed significantly to the broader building of capacity in clinical research in foot and ankle rheumatology. We believe the model has potential to be transferable across health disciplines and on national and international scales

Triangle-Free Penny Graphs: Degeneracy, Choosability, and Edge Count

We show that triangle-free penny graphs have degeneracy at most two, list coloring number (choosability) at most three, diameter $D=\Omega(\sqrt n)$, and at most $\min\bigl(2n-\Omega(\sqrt n),2n-D-2\bigr)$ edges.Comment: 10 pages, 2 figures. To appear at the 25th International Symposium on Graph Drawing and Network Visualization (GD 2017

Structure of a patient-derived antibody in complex with allergen reveals simultaneous conventional and superantigen-like recognition

Antibodies classically bind antigens via their complementarity-determining regions, but an alternative mode of interaction involving V-domain framework regions has been observed for some B cell "superantigens." We report the crystal structure of an antibody employing both modes of interaction simultaneously and binding two antigen molecules. This human antibody from an allergic individual binds to the grass pollen allergen Phl p 7. Not only are two allergen molecules bound to each antibody fragment (Fab) but also each allergen molecule is bound by two Fabs: One epitope is recognized classically, the other in a superantigen-like manner. A single allergen molecule thus cross-links two identical Fabs, contrary to the one-antibody-one-epitope dogma, which dictates that a dimeric allergen at least is required for this to occur. Allergens trigger immediate hypersensitivity reactions by cross-linking receptor-bound IgE molecules on effector cells. We found that monomeric Phl p 7 induced degranulation of basophils sensitized solely with this monoclonal antibody expressed as an IgE, demonstrating that the dual specificity has functional consequences. The monomeric state of Phl p 7 and two structurally related allergens was confirmed by size-exclusion chromatography and multiangle laser light scattering, and the results were supported by degranulation studies with the related allergens, a second patient-derived allergen-specific antibody lacking the nonclassical binding site, and mutagenesis of the nonclassically recognized allergen epitope. The antibody dual reactivity and cross-linking mechanism not only have implications for understanding allergenicity and allergen potency but, importantly, also have broader relevance to antigen recognition by membrane Ig and cross-linking of the B cell receptor

The Structure of Winds in AGB Stars

Most dusty winds are described by a set of similarity functions of a single independent variable that can be chosen as the overall optical depth at visual. The self-similarity implies general scaling relations among the system parameters, in agreement with observations. Dust drift through the gas has a major impact on the structure of most winds.Comment: To appear in proc. of "Workshop on Mass-Losing Pulsating Stars and their Circumstellar Matter", Sendai, Japan (May 2002

Quantum-Dense Metrology

Quantum metrology utilizes entanglement for improving the sensitivity of measurements. Up to now the focus has been on the measurement of just one out of two non-commuting observables. Here we demonstrate a laser interferometer that provides information about two non-commuting observables, with uncertainties below that of the meter's quantum ground state. Our experiment is a proof-of-principle of quantum dense metrology, and uses the additional information to distinguish between the actual phase signal and a parasitic signal due to scattered and frequency shifted photons. Our approach can be readily applied to improve squeezed-light enhanced gravitational-wave detectors at non-quantum noise limited detection frequencies in terms of a sub shot-noise veto-channel.Comment: 5 pages, 3 figures; includes supplementary material