The impact and user experience of a student-led clinic providing preventative services.

OBJECTIVES: Preventative services are required to address the risk factors for chronic conditions such as cardiovascular disease. The National Health Service Health Checks in England were introduced to provide such services. One School of Pharmacy established a student-led clinic to provide this service to the local community. The clinic was provided by undergraduate pharmacy students and delivered free of charge within a central city locality. The aim was to explore the impact of the clinic on user thoughts and motivations around healthy living and investigate user experience. METHODS: A sequential explanatory mixed methods approach was used consisting of a survey that measured users' thoughts about their health and well-being and experience of the clinic. Qualitative interviews explored the user experience and barriers and facilitators to making healthier lifestyle choices. RESULTS: One hundred and fifty-four members of the public accessed the clinic over the evaluative period. Ninety-six (60%) completed the pre-post survey and 12 participated in follow-up interviews. Users reported statistically significant improvements in how informed, competent and motivated they felt towards making healthier lifestyle choices after the clinic consultation. Interview findings highlighted the positive user experience, reported appreciation for clinic accessibility, availability of healthy lifestyle education, and a desire for more preventative services being as readily available. CONCLUSIONS: The student-led clinic has demonstrated positive impacts on user experience, knowledge, competence, and motivation to make healthier lifestyle choices. The clinic provides proof-of-concept for pharmacy students to deliver preventative community services that aim to improve population health at a time when primary care is experiencing unprecedented challenges.

CellPAINT: Turnkey Illustration of Molecular Cell Biology.

CellPAINT is an interactive digital tool that allows non-expert users to create illustrations of the molecular structure of cells and viruses. We present a new release with several key enhancements, including the ability to generate custom ingredients from structure information in the Protein Data Bank, and interaction, grouping, and locking functions that streamline the creation of assemblies and illustration of large, complex scenes. An example of CellPAINT as a tool for hypothesis generation in the interpretation of cryoelectron tomograms is presented. CellPAINT is freely available at http://ccsb.scripps.edu/cellpaint.

Examination of the efficacy of small genetic panels in genomic conservation of companion animal populations.

In many ways, dogs are an ideal model for the study of genetic erosion and population recovery, problems of major concern in the field of conservation genetics. Genetic diversity in many dog breeds has been declining systematically since the beginning of the 1800s, when modern breeding practices came into fashion. As such, inbreeding in domestic dog breeds is substantial and widespread and has led to an increase in recessive deleterious mutations of high effect as well as general inbreeding depression. Pedigrees can in theory be used to guide breeding decisions, though are often incomplete and do not reflect the full history of inbreeding. Small microsatellite panels are also used in some cases to choose mating pairs to produce litters with low levels of inbreeding. However, the long-term impact of such practices has not been thoroughly evaluated. Here, we use forward simulation on a model of the dog genome to examine the impact of using limited marker panels to guide pairwise mating decisions on genome-wide population-level genetic diversity. Our results suggest that in unmanaged populations, where breeding decisions are made at the pairwise-rather than population-level, such panels can lead to accelerated loss of genetic diversity at genome regions unlinked to panel markers, compared to random mating. These results demonstrate the importance of genome-wide genetic panels for managing and conserving genetic diversity in dogs and other companion animals.

Molecular architecture, polar targeting and biogenesis of the Legionella Dot/Icm T4SS.

Legionella pneumophila survives and replicates inside host cells by secreting ~300 effectors through the defective in organelle trafficking (Dot)/intracellular multiplication (Icm) type IVB secretion system (T4BSS). Here, we used complementary electron cryotomography and immunofluorescence microscopy to investigate the molecular architecture and biogenesis of the Dot/Icm secretion apparatus. Electron cryotomography mapped the location of the core and accessory components of the Legionella core transmembrane subcomplex, revealing a well-ordered central channel that opens into a large, windowed secretion chamber with an unusual 13-fold symmetry. Immunofluorescence microscopy deciphered an early-stage assembly process that begins with the targeting of Dot/Icm components to the bacterial poles. Polar targeting of this T4BSS is mediated by two Dot/Icm proteins, DotU and IcmF, that, interestingly, are homologues of the T6SS membrane complex components TssL and TssM, suggesting that the Dot/Icm T4BSS is a hybrid system. Together, these results revealed that the Dot/Icm complex assembles in an 'axial-to-peripheral' pattern.

Recovery of layered tissue optical properties from spatial frequency-domain spectroscopy and a deterministic radiative transport solver.

We present a method to recover absorption and reduced scattering spectra for each layer of a two-layer turbid media from spatial frequency-domain spectroscopy data. We focus on systems in which the thickness of the top layer is less than the transport mean free path ( 0.1 - 0.8l * ) . We utilize an analytic forward solver, based upon the N'th-order spherical harmonic expansion with Fourier decomposition ( SHEFN ) method in conjunction with a multistage inverse solver. We test our method with data obtained using spatial frequency-domain spectroscopy with 32 evenly spaced wavelengths within λ = 450 to 1000 nm on six-layered tissue phantoms with distinct optical properties. We demonstrate that this approach can recover absorption and reduced scattering coefficient spectra for both layers with accuracy comparable with current Monte Carlo methods but with lower computational cost and potential flexibility to easily handle variations in parameters such as the scattering phase function or material refractive index. To our knowledge, this approach utilizes the most accurate deterministic forward solver used in such problems and can successfully recover properties from a two-layer media with superficial layer thicknesses.

CellPAINT: Interactive Illustration of Dynamic Mesoscale Cellular Environments.

CellPAINT allows nonexpert users to create interactive mesoscale illustrations that integrate a variety of biological data. Like popular digital painting software, scenes are created using a palette of molecular "brushes." The current release allows creation of animated scenes with an HIV virion, blood plasma, and a simplified T-cell.

A Self-Assisting Protein Folding Model for Teaching Structural Molecular Biology.

Structural molecular biology is now becoming part of high school science curriculum thus posing a challenge for teachers who need to convey three-dimensional (3D) structures with conventional text and pictures. In many cases even interactive computer graphics does not go far enough to address these challenges. We have developed a flexible model of the polypeptide backbone using 3D printing technology. With this model we have produced a polypeptide assembly kit to create an idealized model of the Triosephosphate isomerase mutase enzyme (TIM), which forms a structure known as TIM barrel. This kit has been used in a laboratory practical where students perform a step-by-step investigation into the nature of protein folding, starting with the handedness of amino acids to the formation of secondary and tertiary structure. Based on the classroom evidence we collected, we conclude that these models are valuable and inexpensive resource for teaching structural molecular biology.

3D Printing of Molecular Models.

Physical molecular models have played a valuable role in our understanding of the invisible nano-scale world. We discuss 3D printing and its use in producing models of the molecules of life. Complex biomolecular models, produced from 3D printed parts, can demonstrate characteristics of molecular structure and function, such as viral self-assembly, protein folding, and DNA structure. Advances in computer and user interface technology have enabled physical molecular models to combine with augmented reality to bridge the physical with the computational world.

Coupled forward-adjoint Monte Carlo simulation of spatial-angular light fields to determine optical sensitivity in turbid media.

We present a coupled forward-adjoint Monte Carlo (cFAMC) method to determine the spatially resolved sensitivity distributions produced by optical interrogation of three-dimensional (3-D) tissue volumes. We develop a general computational framework that computes the spatial and angular distributions of the forward-adjoint light fields to provide accurate computations in mesoscopic tissue volumes. We provide full computational details of the cFAMC method and provide results for low- and high-scattering tissues probed using a single pair of optical fibers. We examine the effects of source-detector separation and orientation on the sensitivity distributions and consider how the degree of angular discretization used in the 3-D tissue model impacts the accuracy of the resulting absorption sensitivity profiles. We discuss the value of such computations for optical imaging and the design of optical measurements.

Genome sequences of five b1 subcluster mycobacteriophages.

Mycobacteriophages infect members of the Mycobacterium genus in the phylum Actinobacteria and exhibit remarkable diversity. Genome analysis groups the thousands of known mycobacteriophages into clusters, of which the B1 subcluster is currently the third most populous. We report the complete genome sequences of five additional members of the B1 subcluster.

Complete Genome Sequences of Five Paenibacillus larvae Bacteriophages.

Paenibacillus larvae is a pathogen of honeybees that causes American foulbrood (AFB). We isolated bacteriophages from soil containing bee debris collected near beehives in Utah. We announce five high-quality complete genome sequences, which represent the first completed genome sequences submitted to GenBank for any P. larvae bacteriophage.

Radiative transport produced by oblique illumination of turbid media with collimated beams.

We examine the general problem of light transport initiated by oblique illumination of a turbid medium with a collimated beam. This situation has direct relevance to the analysis of cloudy atmospheres, terrestrial surfaces, soft condensed matter, and biological tissues. We introduce a solution approach to the equation of radiative transfer that governs this problem, and develop a comprehensive spherical harmonics expansion method utilizing Fourier decomposition (SHEF(N)). The SHEF(N) approach enables the solution of problems lacking azimuthal symmetry and provides both the spatial and directional dependence of the radiance. We also introduce the method of sequential-order smoothing that enables the calculation of accurate solutions from the results of two sequential low-order approximations. We apply the SHEF(N) approach to determine the spatial and angular dependence of both internal and boundary radiances from strongly and weakly scattering turbid media. These solutions are validated using more costly Monte Carlo simulations and reveal important insights regarding the evolution of the radiant field generated by oblique collimated beams spanning ballistic and diffusely scattering regimes.

Analysis of single Monte Carlo methods for prediction of reflectance from turbid media.

Starting from the radiative transport equation we derive the scaling relationships that enable a single Monte Carlo (MC) simulation to predict the spatially- and temporally-resolved reflectance from homogeneous semi-infinite media with arbitrary scattering and absorption coefficients. This derivation shows that a rigorous application of this single Monte Carlo (sMC) approach requires the rescaling to be done individually for each photon biography. We examine the accuracy of the sMC method when processing simulations on an individual photon basis and also demonstrate the use of adaptive binning and interpolation using non-uniform rational B-splines (NURBS) to achieve order of magnitude reductions in the relative error as compared to the use of uniform binning and linear interpolation. This improved implementation for sMC simulation serves as a fast and accurate solver to address both forward and inverse problems and is available for use at http://www.virtualphotonics.org/.

Accurate and efficient Monte Carlo solutions to the radiative transport equation in the spatial frequency domain.

We present an approach to solving the radiative transport equation (RTE) for layered media in the spatial frequency domain (SFD) using Monte Carlo (MC) simulations. This is done by obtaining a complex photon weight from analysis of the Fourier transform of the RTE. We also develop a modified shortcut method that enables a single MC simulation to efficiently provide RTE solutions in the SFD for any number of spatial frequencies. We provide comparisons between the modified shortcut method and conventional discrete transform methods for SFD reflectance. Further results for oblique illumination illustrate the potential diagnostic utility of the SFD phase-shifts for analysis of layered media.