What's been tried: a curated catalogue of efforts to improve access to general practice.

Background: Although increasing numbers of appointments are being provided, public satisfaction with access to UK general practice is declining. Previous attempts to improve access have not been systematically collated.

Aim: We aimed to identify interventions to improve access to general practice in the UK, to organise these interventions into thematic categories, and to identify which aspects of access are targeted.

Functional and spectroscopic approaches to determining thermal limitations of Rieske oxygenases.

The biotechnological potential of Rieske Oxygenases (ROs) and their cognate reductases remains unmet, in part because these systems can be functionally short-lived. Here, we describe a set of experiments aimed at identifying both the functional and structural stability limitations of ROs, using terephthalate (TPA) dioxygenase (from Comamonas strain E6) as a model system. Successful expression and purification of a cofactor-complete, histidine-tagged TPA dioxygenase and reductase protein system requires induction with the Escherichia coli host at stationary phase as well as a chaperone inducing cold-shock and supplementation with additional iron, sulfur, and flavin.

Understanding access to general practice through the lens of candidacy: a critical review of the literature.

Background: Dominant conceptualisations of access to health care are limited, framed in terms of speed and supply. The Candidacy Framework offers a more comprehensive approach, identifying diverse influences on how access is accomplished.

Aim: To characterise how the Candidacy Framework can explain access to general practice - an increasingly fraught area of public debate and policy.

Understanding the stability of a plastic-degrading Rieske iron oxidoreductase system.

Rieske oxygenases (ROs) are a diverse metalloenzyme class with growing potential in bioconversion and synthetic applications. We postulated that ROs are nonetheless underutilized because they are unstable. Terephthalate dioxygenase (TPA PDB ID 7Q05) is a structurally characterized heterohexameric αβ RO that, with its cognate reductase (TPA), catalyzes the first intracellular step of bacterial polyethylene terephthalate plastic bioconversion.

Photophysical image analysis: Unsupervised probabilistic thresholding for images from electron-multiplying charge-coupled devices.

We introduce the concept photophysical image analysis (PIA) and an associated pipeline for unsupervised probabilistic image thresholding for images recorded by electron-multiplying charge-coupled device (EMCCD) cameras. We base our approach on a closed-form analytic expression for the characteristic function (Fourier-transform of the probability mass function) for the image counts recorded in an EMCCD camera, which takes into account both stochasticity in the arrival of photons at the imaging camera and subsequent noise induced by the detection system of the camera. The only assumption in our method is that the background photon arrival to the imaging system is described by a stationary Poisson process (we make no assumption about the photon statistics for the signal).

Geometry-Dependent Elastic Flow Dynamics in Micropillar Arrays.

Regular device-scale DNA waves for high DNA concentrations and flow velocities have been shown to emerge in quadratic micropillar arrays with potentially strong relevance for a wide range of microfluidic applications. Hexagonal arrays constitute another geometry that is especially relevant for the microfluidic pulsed-field separation of DNA. Here, we report on the differences at the micro and macroscopic scales between the resulting wave patterns for these two regular array geometries and one disordered array geometry.

Injury Profile in Youth Female Athletes: A Systematic Review and Meta-Analysis.

Background: An increasing number of epidemiological studies assessing the incidence, prevalence and severity of injury in youth female sport are available. However, no study has sought to synthesise the current evidence base across all youth female sport. As such, a systematic review and meta-analysis of injury in this cohort is necessary to understand the diversity of injury and its associated burden between sports in addition to identifying the density of research available.

Quantification of growth and nutrient consumption of bacterial and fungal cultures in microfluidic microhabitat models.

Understanding microbes in nature requires consideration of their microenvironment. Here, we present a protocol for quantifying biomass and nutrient degradation of bacterial and fungal cultures (Pseudomonas putida and Coprinopsis cinerea, respectively) in microfluidics. We describe steps for mask design and fabrication, master printing, polydimethylsiloxane chip fabrication, and chip inoculation and imaging using fluorescence microscopy.

Contrasting terrestrial and marine ecospace dynamics after the end-Triassic mass extinction event.

Mass extinctions have fundamentally altered the structure of the biosphere throughout Earth's history. The ecological severity of mass extinctions is well studied in marine ecosystems by categorizing marine taxa into functional groups based on 'ecospace' approaches, but the ecological response of terrestrial ecosystems to mass extinctions is less well understood due to the lack of a comparable methodology. Here, we present a new terrestrial ecospace framework that categorizes fauna into functional groups as defined by tiering, motility and feeding traits.

Using symmetry to control viscoelastic waves in pillar arrays.

Solutions of macromolecules exhibit viscoelastic properties and unlike Newtonian fluids, they may break time-reversal symmetry at low Reynolds numbers resulting in elastic turbulence. Furthermore, under some conditions, instead of the chaotic turbulence, the result is large-scale waves in the form of cyclic spatial and temporal concentration variations, as has been shown for macromolecular DNA flowing in microfluidic pillar arrays. We here demonstrate how altering the symmetry of the individual pillars can be used to influence the symmetry of these waves.

Fluorescence Microscopy of Nanochannel-Confined DNA.

Stretching of DNA in nanoscale confinement allows for several important studies. The genetic contents of the DNA can be visualized on the single DNA molecule level, and the polymer physics of confined DNA and also DNA/protein and other DNA/DNA-binding molecule interactions can be explored. This chapter describes the basic steps to fabricate the nanostructures, perform the experiments, and analyze the data.

Exposure to polystyrene nanoplastics reduces bacterial and fungal biomass in microfabricated soil models.

Nanoplastics have been proven to induce toxicity in diverse organisms, yet their effect on soil microbes like bacteria and fungi remains largely unexplored. In this paper, we used micro-engineered soil models to investigate the effect of polystyrene (PS) nanospheres on Pseudomonas putida and Coprinopsis cinerea. Specifically, we explored the effects of increasing concentrations of 60 nm carboxylated bovine serum albumin (BSA) coated nanospheres (0, 0.

An optimized IL-12-Fc expands its therapeutic window, achieving strong activity against mouse tumors at tolerable drug doses.

Background: Interleukin-12 (IL-12) has emerged as one of the most potent cytokines for tumor immunotherapy due to its ability to induce interferon γ (IFNγ) and polarize Th1 responses. Clinical use of IL-12 has been limited by a short half-life and narrow therapeutic index.

Methods: We generated a monovalent, half-life-extended IL-12-Fc fusion protein, mDF6006, engineered to retain the high potency of native IL-12 while significantly expanding its therapeutic window.

Habitat complexity affects microbial growth in fractal maze.

The great variety of earth's microorganisms and their functions are attributed to the heterogeneity of their habitats, but our understanding of the impact of this heterogeneity on microbes is limited at the microscale. In this study, we tested how a gradient of spatial habitat complexity in the form of fractal mazes influenced the growth, substrate degradation, and interactions of the bacterial strain Pseudomonas putida and the fungal strain Coprinopsis cinerea. These strains responded in opposite ways: complex habitats strongly reduced fungal growth but, in contrast, increased the abundance of bacteria.

Short and long-range cyclic patterns in flows of DNA solutions in microfluidic obstacle arrays.

We observe regular patterns emerging across multiple length scales with high-concentration DNA solutions in microfluidic pillar arrays at low Reynolds numbers and high Deborah numbers. Interacting vortices between pillars lead to long-range order in the form of large travelling waves consisting of DNA at high concentration and extension. Waves are formed in quadratic arrays of pillars, while randomizing the position of the pillar in each unit cell of a quadratic array leads to suppression of the long-range patterns.

Use of dielectrophoresis for directing T cells to microwells before nanostraw transfection: modelling and experiments.

Nanostraw substrates have great potential for achieving minimally invasive cell transfection. Cells located on the nanostraw substrate are subjected to mild DC electric pulses applied across the nanostraw substrate, which open pores in the cell membrane on top of the nanostraws and drives charged cargo through these pores electrophoresis. However, with this method, the current may leak through uncovered nanostraws, thereby decreasing the desired effect in the cell-covered nanostraws.

High-Throughput Separation of Long DNA in Deterministic Lateral Displacement Arrays.

Length-based separation of DNA remains as relevant today as when gel electrophoresis was introduced almost 100 years ago. While new, long-read genomics technologies have revolutionised accessibility to powerful genomic data, the preparation of samples has not proceeded at the same pace, with sample preparation often constituting a considerable bottleneck, both in time and difficulty. Microfluidics holds great potential for automated, sample-to-answer analysis via the integration of preparatory and analytical steps, but for this to be fully realised, more versatile, powerful and integrable unit operations, such as separation, are essential.

The incidence and burden of injuries in elite English youth female soccer players.

This study aimed to investigate the incidence, severity and burden of injury in English elite youth female soccer players. Qualified therapists at six English girls' academies prospectively recorded all injuries that required medical attention or caused time loss for matches and training in 375 elite youth female soccer players (under-10 [U10], U12, U14 and U16) during the 2019/2020 season. One hundred- and eleven time-loss injuries (52 from training, 59 from matches) were sustained, resulting in 1,946 days absent (779 days from training injuries, 1,167 days from match injuries) from soccer activities.

Nanoscale binding site localization by molecular distance estimation on native cell surfaces using topological image averaging.

Antibody binding to cell surface proteins plays a crucial role in immunity, and the location of an epitope can altogether determine the immunological outcome of a host-target interaction. Techniques available today for epitope identification are costly, time-consuming, and unsuited for high-throughput analysis. Fast and efficient screening of epitope location can be useful for the development of therapeutic monoclonal antibodies and vaccines.

The anthropometric and physical qualities of women's rugby league Super League and international players; identifying differences in playing position and level.

Participation in women's rugby league has been growing since the foundation of the English women's rugby league Super League in 2017. However, the evidence base to inform women's rugby league remains sparse. This study provides the largest quantification of anthropometric and physical qualities of women's rugby league players to date, identifying differences between positions (forwards & backs) and playing level (Women's Super League [WSL] vs.

Habitat geometry in artificial microstructure affects bacterial and fungal growth, interactions, and substrate degradation.

Microhabitat conditions determine the magnitude and speed of microbial processes but have been challenging to investigate. In this study we used microfluidic devices to determine the effect of the spatial distortion of a pore space on fungal and bacterial growth, interactions, and substrate degradation. The devices contained channels differing in bending angles and order.

Microfluidic Obstacle Arrays Induce Large Reversible Shape Change in Red Blood Cells.

Red blood cell (RBC) shape change under static and dynamic shear stress has been a source of interest for at least 50 years. High-speed time-lapse microscopy was used to observe the rate of deformation and relaxation when RBCs are subjected to periodic shear stress and deformation forces as they pass through an obstacle. We show that red blood cells are reversibly deformed and take on characteristic shapes not previously seen in physiological buffers when the maximum shear stress was between 2.

A simple, open and extensible gating Control unit for cardiac and respiratory synchronisation control in small animal MRI and demonstration of its robust performance in steady-state maintained CINE-MRI.

Prospective cardiac gating during MRI is hampered by electromagnetic induction from the rapidly switched imaging gradients into the ECG detection circuit. This is particularly challenging in small animal MRI, as higher heart rates combined with a smaller myocardial mass render routine ECG detection challenging. We have developed an open-hardware system that enables continuously running MRI scans to be performed in conjunction with cardio-respiratory gating such that the relaxation-weighted steady state magnetisation is maintained throughout the scan.

Cell Sorting Using Electrokinetic Deterministic Lateral Displacement.

We show that by combining deterministic lateral displacement (DLD) with electrokinetics, it is possible to sort cells based on differences in their membrane and/or internal structures. Using heat to deactivate cells, which change their viability and structure, we then demonstrate sorting of a mixture of viable and non-viable cells for two different cell types. For the size change due to deactivation is insufficient to allow size-based DLD separation.