Field testing methodology for investigating the effect of systemic insecticides on honey bees

contribution to session IVTest methodolog

Phylogenetic Analysis of Kindlins Suggests Subfunctionalization of an Ancestral Unduplicated Kindlin into Three Paralogs in Vertebrates

Kindlin proteins represent a newly discovered family of evolutionarily conserved FERM domain-containing proteins. This family includes three highly conserved proteins: Kindlin-1, Kindlin-2 and Kindlin-3. All three Kindlin proteins are associated with focal adhesions and are involved in integrin activation. The FERM domain of each Kindlin is bipartite and plays a key role in integrin activation. We herein explore for the first time the evolutionary history of these proteins. The phylogeny of the Kindlins suggests a single ancestral Kindlin protein present in even the earliest metazoan ie, hydra. This protein then underwent duplication events in insects and also experienced genome duplication in vertebrates, leading to the Kindlin family. A comparative study of the Kindlin paralogs showed that Kindlin-2 is the slowest evolving protein among the three family members. The analysis of synonymous and non-synonymous substitutions in orthologous Kindlin sequences in different species showed that all three Kindlins have been evolving under the influence of purifying selection. The expression pattern of Kindlins along with phylogenetic studies supports the subfunctionalization model of gene duplication

Symmetric and asymmetric action integration during cooperative object manipulation in virtual environments

Cooperation between multiple users in a virtual environment (VE) can take place at one of three levels. These are defined as where users can perceive each other (Level 1), individually change the scene (Level 2), or simultaneously act on and manipulate the same object (Level 3). Despite representing the highest level of cooperation, multi-user object manipulation has rarely been studied. This paper describes a behavioral experiment in which the piano movers' problem (maneuvering a large object through a restricted space) was used to investigate object manipulation by pairs of participants in a VE. Participants' interactions with the object were integrated together either symmetrically or asymmetrically. The former only allowed the common component of participants' actions to take place, but the latter used the mean. Symmetric action integration was superior for sections of the task when both participants had to perform similar actions, but if participants had to move in different ways (e.g., one maneuvering themselves through a narrow opening while the other traveled down a wide corridor) then asymmetric integration was superior. With both forms of integration, the extent to which participants coordinated their actions was poor and this led to a substantial cooperation overhead (the reduction in performance caused by having to cooperate with another person)

How, in what contexts, and why do quality dashboards lead to improvements in care quality in acute hospitals? Protocol for a realist feasibility evaluation

Introduction: National audits are used to monitor care quality and safety and are anticipated to reduce unexplained variations in quality by stimulating quality improvement (QI). However, variation within and between providers in the extent of engagement with national audits means that the potential for national audit data to inform QI is not being realised. This study will undertake a feasibility evaluation of QualDash, a quality dashboard designed to support clinical teams and managers to explore data from two national audits, the Myocardial Ischaemia National Audit Project (MINAP) and the Paediatric Intensive Care Audit Network (PICANet). Methods and analysis: Realist evaluation, which involves building, testing and refining theories of how an intervention works, provides an overall framework for this feasibility study. Realist hypotheses that describe how, in what contexts, and why QualDash is expected to provide benefit will be tested across five hospitals. A controlled interrupted time series analysis, using key MINAP and PICANet measures, will provide preliminary evidence of the impact of QualDash, while ethnographic observations and interviews over 12 months will provide initial insight into contexts and mechanisms that lead to those impacts. Feasibility outcomes include the extent to which MINAP and PICANet data are used, data completeness in the audits, and the extent to which participants perceive QualDash to be useful and express the intention to continue using it after the study period. Ethics and dissemination: The study has been approved by the University of Leeds School of Healthcare Research Ethics Committee. Study results will provide an initial understanding of how, in what contexts, and why quality dashboards lead to improvements in care quality. These will be disseminated to academic audiences, study participants, hospital IT departments and national audits. If the results show a trial is feasible, we will disseminate the QualDash software through a stepped wedge cluster randomised trial

Visual parameter optimisation for biomedical image processing

Background: Biomedical image processing methods require users to optimise input parameters to ensure high quality output. This presents two challenges. First, it is difficult to optimise multiple input parameters for multiple input images. Second, it is difficult to achieve an understanding of underlying algorithms, in particular, relationships between input and output. Results: We present a visualisation method that transforms users’ ability to understand algorithm behaviour by integrating input and output, and by supporting exploration of their relationships. We discuss its application to a colour deconvolution technique for stained histology images and show how it enabled a domain expert to identify suitable parameter values for the deconvolution of two types of images, and metrics to quantify deconvolution performance. It also enabled a breakthrough in understanding by invalidating an underlying assumption about the algorithm. Conclusions: The visualisation method presented here provides analysis capability for multiple inputs and outputs in biomedical image processing that is not supported by previous analysis software. The analysis supported by our method is not feasible with conventional trial-and-error approaches

Children's traditional ecological knowledge of wild food resources: a case study in a rural village in Northeast Thailand

Consuming wild foods is part of the food ways of people in many societies, including farming populations throughout the world. Knowledge of non-domesticated food resources is part of traditional and tacit ecological knowledge, and is largely transmitted through socialization within cultural and household contexts. The context of this study, a small village in Northeast Thailand, is one where the community has experienced changes due to the migration of the parental generation, with the children being left behind in the village to be raised by their grandparents

Linear and Nonlinear Ultrasonic Properties of Granular Soils

The ultrasonic pulse transmission method (100-500 kHz) was adapted to measure compressional (P) and shear (S) wave velocities for synthetic soils fabricated from quartz-clay and quartz-peat mixtures. Velocities were determined as samples were loaded by small (up to 0.1 MPa) uniaxial stress to determine how stress at grain contacts affects ave amplitudes, velocities, and frequency content. Samples were fabricated from quartz sand mixed with either a swelling clay or peat (natural cellulose). P velocities in these dry synthetic soil samples were low, ranging from about 230 to 430 m/s for pure sand, about 91 to 420 m/s for sand-peat mixtures, and about 230 to 470 m/s for dry sand-clay mixtures. S velocities were about half of the P velocity in most cases, about 130 to 250 m/s for pure sand, about 75-220 m/s for sand-peat mixtures, and about 88-220 m/s for dry sand-clay mixtures. These experiments demonstrate that P and S velocities are sensitive to the amount and type of admixed second phase at low concentrations. They found that dramatic increases in all velocities occur with small uniaxial loads, indicating strong nonlinearity of the acoustic properties. Composition and grain packing contribute to the mechanical response at grain contacts and the nonlinear response at low stresses

Effect of display resolution on time to diagnosis with virtual pathology slides in a systematic search task

Performing diagnoses using virtual slides can take pathologists significantly longer than with glass slides, presenting a significant barrier to the use of virtual slides in routine practice. Given the benefits in pathology workflow efficiency and safety that virtual slides promise, it is important to understand reasons for this difference and identify opportunities for improvement. The effect of display resolution on time to diagnosis with virtual slides has not previously been explored. The aim of this study was to assess the effect of display resolution on time to diagnosis with virtual slides. Nine pathologists participated in a counterbalanced crossover study, viewing axillary lymph node slides on a microscope, a 23-in 2.3-megapixel single-screen display and a three-screen 11-megapixel display consisting of three 27-in displays. Time to diagnosis and time to first target were faster on the microscope than on the single and three-screen displays. There was no significant difference between the microscope and the three-screen display in time to first target, while the time taken on the single-screen display was significantly higher than that on the microscope. The results suggest that a digital pathology workstation with an increased number of pixels may make it easier to identify where cancer is located in the initial slide overview, enabling quick location of diagnostically relevant regions of interest. However, when a comprehensive, detailed search of a slide has to be made, increased resolution may not offer any additional benefit

A phase I dose-escalation study of enzalutamide in combination with the AKT inhibitor AZD5363 (capivasertib) in patients with metastatic castration-resistant prostate cancer.

Background Activation of the PI3K/AKT/mTOR pathway through loss of phosphatase and tensin homolog (PTEN) occurs in approximately 50% of patients with metastatic castration-resistant prostate cancer (mCRPC). Recent evidence suggests that combined inhibition of the androgen receptor (AR) and AKT may be beneficial in mCRPC with PTEN loss.Patients and methods mCRPC patients who previously failed abiraterone and/or enzalutamide, received escalating doses of AZD5363 (capivasertib) starting at 320 mg twice daily (b.i.d.) given 4 days on and 3 days off, in combination with enzalutamide 160 mg daily. The co-primary endpoints were safety/tolerability and determining the maximum tolerated dose and recommended phase II dose; pharmacokinetics, antitumour activity, and exploratory biomarker analysis were also evaluated.Results Sixteen patients were enrolled, 15 received study treatment and 13 were assessable for dose-limiting toxicities (DLTs). Patients were treated at 320, 400, and 480 mg b.i.d. dose levels of capivasertib. The recommended phase II dose identified for capivasertib was 400 mg b.i.d. with 1/6 patients experiencing a DLT (maculopapular rash) at this level. The most common grade ≥3 adverse events were hyperglycemia (26.7%) and rash (20%). Concomitant administration of enzalutamide significantly decreased plasma exposure of capivasertib, though this did not appear to impact pharmacodynamics. Three patients met the criteria for response (defined as prostate-specific antigen decline ≥50%, circulating tumour cell conversion, and/or radiological response). Responses were seen in patients with PTEN loss or activating mutations in AKT, low or absent AR-V7 expression, as well as those with an increase in phosphorylated extracellular signal-regulated kinase (pERK) in post-exposure samples.Conclusions The combination of capivasertib and enzalutamide is tolerable and has antitumour activity, with all responding patients harbouring aberrations in the PI3K/AKT/mTOR pathway.Clinical trial number NCT02525068