'Dear Doctor': a randomised controlled trial of a text message intervention to reduce burnout in trainee anaesthetists.

One in four doctors in training in the UK reports feeling 'burnt out' due to their work and similar figures are reported in other countries. This two-group non-blinded randomised controlled trial aimed to determine if a novel text message intervention could reduce burnout and increase well-being in UK trainee anaesthetists. A total of 279 trainee anaesthetists (Core Training Year 2, Specialty Training Years 3 or 4) were included.

Deformations and Ruptures in Human Lenses With Cortical Cataract Subjected to Ex Vivo Simulated Accommodation.

Purpose: Human cortical opacities are most commonly accompanied by changes in lens fiber structure in the equatorial region at the lens nucleus-cortex interface. Cortex and nucleus have different elastic properties, which change with age. We therefore subjected ex vivo lenses to simulated accommodation and studied the internal deformations to better understand the mechanism of cortical cataract formation.

Identifying the predictors of avoidable emergency department attendance after contact with the NHS 111 phone service: analysis of 16.6 million calls to 111 in England in 2015-2017.

Objectives: To measure the frequency of patients making avoidable emergency department (ED) attendances after contact with NHS 111 and to examine whether these attendances can be predicted reliably.

Design: Analysis of 16 563 946 calls made to 111, where each call was linked with a record of whether the patient attended ED within 24 hours.

Setting: All regions of England from March 2015 to October 2017.

Anterior lens capsule strains during simulated accommodation in porcine eyes.

Experimental protocols have been developed to measure the spatial variation of the mechanical strains induced in the lens capsule during ex vivo lens stretching. The paper describes the application of these protocols to porcine lenses. The deformations and mechanical strains developed in the anterior capsule during each experiment were determined using full field digital image correlation techniques, by means of a speckle pattern applied to the lens surface.

Equatorial wrinkles in the human lens capsule.

Equatorial wrinkles, or crenations, have been previously observed around the equator in coronal images of the human ocular lens. However, wrinkles are typically not apparent when the lens is viewed from saggital directions. In the current paper, the existence and geometry of these wrinkles is shown to be consistent with a mechanical model of the isolated lens, in which the capsule is held in a state of residual tension by a spatially uniform internal pressure.

Finite element modelling of radial lentotomy cuts to improve the accommodation performance of the human lens.

Purpose: The use of a femtosecond laser to form planes of cavitation bubbles within the ocular lens has been proposed as a potential treatment for presbyopia. The intended purpose of these planes of cavitation bubbles (referred to in this paper as 'cutting planes') is to increase the compliance of the lens, with a consequential increase in the amplitude of accommodation. The current paper describes a computational modelling study, based on three-dimensional finite element analysis, to investigate the relationship between the geometric arrangement of the cutting planes and the resulting improvement in lens accommodation performance.

The mechanical response of the porcine lens to a spinning test.

The pig lens has been used as a model for presbyopia as pigs lack accommodative ability. Previous studies using microindentation have indicated that the shear modulus distribution is qualitatively similar to that of the aged human lens and that the lens does not alter its refractive power due to equatorial stretching. A lens spinning test was used to determine whether prior lens stiffness data obtained from a sectioned porcine lens were reliable and whether the testing conditions significantly influence the lens' mechanical properties.

Experimental protocols for ex vivo lens stretching tests to investigate the biomechanics of the human accommodation apparatus.

Purpose: To explore alternative experimental protocols to investigate the biomechanical behavior of the crystalline lens and zonules using ex vivo stretching.

Methods: Radial stretching tests were conducted on the anterior segment (consisting of lens, zonules, ciliary body, and sclera) of four pairs of presbyopic human donor eyes. A simple mechanical model is used to describe the behavior of the anterior segment when tested in this way.

Finite element implementation of a multiscale model of the human lens capsule.

An axisymmetric finite element implementation of a previously described structural constitutive model for the human lens capsule (Burd in Biomech Model Mechanobiol 8(3):217-231, 2009) is presented. This constitutive model is based on a hyperelastic approach in which the network of collagen IV within the capsule is represented by an irregular hexagonal planar network of hyperelastic bars, embedded in a hyperelastic matrix. The paper gives a detailed specification of the model and the periodic boundary conditions adopted for the network component.

The genome of Shigella dysenteriae strain Sd1617 comparison to representative strains in evaluating pathogenesis.

We sequenced and analyzed Shigella dysenteriae strain Sd1617 serotype 1 that is widely used as model strain for vaccine design, trials and research. A combination of next-generation sequencing platforms and assembly yielded two contigs representing a chromosome size of 4.34 Mb and the large virulence plasmid of 177 kb.

Substantial improvements in methyl ketone production in E. coli and insights on the pathway from in vitro studies.

We previously reported development of a metabolic pathway in Escherichia coli for overproduction of medium-chain methyl ketones (MK), which are relevant to the biofuel and flavor-and-fragrance industries. This MK pathway was a re-engineered version of β-oxidation designed to overproduce β-ketoacyl-CoAs and involved overexpression of the fadM thioesterase gene. Here, we document metabolic engineering modifications that have led to a MK titer of 3.

Discovery of microorganisms and enzymes involved in high-solids decomposition of rice straw using metagenomic analyses.

High-solids incubations were performed to enrich for microbial communities and enzymes that decompose rice straw under mesophilic (35°C) and thermophilic (55°C) conditions. Thermophilic enrichments yielded a community that was 7.5 times more metabolically active on rice straw than mesophilic enrichments.

Engineering of Ralstonia eutropha H16 for autotrophic and heterotrophic production of methyl ketones.

Ralstonia eutropha is a facultatively chemolithoautotrophic bacterium able to grow with organic substrates or H2 and CO2 under aerobic conditions. Under conditions of nutrient imbalance, R. eutropha produces copious amounts of poly[(R)-3-hydroxybutyrate] (PHB).

HipA-triggered growth arrest and β-lactam tolerance in Escherichia coli are mediated by RelA-dependent ppGpp synthesis.

Persistence is a phenomenon whereby a subpopulation of bacterial cells enters a transient growth-arrested state that confers antibiotic tolerance. While entrance into persistence has been linked to the activities of toxin proteins, the molecular mechanisms by which toxins induce growth arrest and the persistent state remain unclear. Here, we show that overexpression of the protein kinase HipA in Escherichia coli triggers growth arrest by activating synthesis of the alarmone guanosine tetraphosphate (ppGpp) by the enzyme RelA, a signal typically associated with amino acid starvation.

Shear modulus measurements on isolated human lens nuclei.

The use of a spinning lens test to determine ex vivo the shear modulus of 22 isolated human lens nuclei with ages ranging from 34 to 63 years is described. In this test procedure, the lens nucleus is spun about its polar axis. Images of the nucleus viewed from directions perpendicular to the polar axis are collected; these are used to quantify the deformations induced in the nucleus by the rotational motion.

Thermophilic enrichment of microbial communities in the presence of the ionic liquid 1-ethyl-3-methylimidazolium acetate.

Aims: The aim of the study was to develop an approach to enrich ionic liquid tolerant micro-organisms that efficiently decompose lignocellulose in a thermophilic and high-solids environment.

Methods And Results: High-solids incubations were conducted, using compost as an inoculum source, to enrich for thermophilic communities that decompose switchgrass in the presence of the ionic liquid 1-ethyl-3-methylimidazolium acetate ([C2mim][OAc]). Ionic liquid levels were increased from 0 to 6% on a total weight basis incrementally.

Carotenoid-based phenotypic screen of the yeast deletion collection reveals new genes with roles in isoprenoid production.

Beside their essential cellular functions, isoprenoids have value as pharmaceuticals, nutriceuticals, pesticides, and fuel alternatives. Engineering microorganisms for production of isoprenoids is relatively easy, sustainable, and cost effective in comparison to chemical synthesis or extraction from natural producers. We introduced genes encoding carotenoid biosynthetic enzymes into the haploid yeast deletion collection to identify gene deletions that improved isoprenoid production.

A thermophilic ionic liquid-tolerant cellulase cocktail for the production of cellulosic biofuels.

Generation of biofuels from sugars in lignocellulosic biomass is a promising alternative to liquid fossil fuels, but efficient and inexpensive bioprocessing configurations must be developed to make this technology commercially viable. One of the major barriers to commercialization is the recalcitrance of plant cell wall polysaccharides to enzymatic hydrolysis. Biomass pretreatment with ionic liquids (ILs) enables efficient saccharification of biomass, but residual ILs inhibit both saccharification and microbial fuel production, requiring extensive washing after IL pretreatment.

Shear modulus data for the human lens determined from a spinning lens test.

The paper describes a program of mechanical testing on donated human eye bank lenses. The principal purpose of the tests was to obtain experimental data on the shear modulus of the lens for use in future computational models of the accommodation process. Testing was conducted using a procedure in which deformations are induced in the lens by spinning it about its polar axis.

Modular engineering of L-tyrosine production in Escherichia coli.

Efficient biosynthesis of L-tyrosine from glucose is necessary to make biological production economically viable. To this end, we designed and constructed a modular biosynthetic pathway for L-tyrosine production in E. coli MG1655 by encoding the enzymes for converting erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP) to L-tyrosine on two plasmids.

An improved spinning lens test to determine the stiffness of the human lens.

It is widely accepted that age-related changes in lens stiffness are significant for the development of presbyopia. However, precise details on the relative importance of age-related changes in the stiffness of the lens, in comparison with other potential mechanisms for the development of presbyopia, have not yet been established. One contributing factor to this uncertainty is the paucity and variability of experimental data on lens stiffness.

Production of tranilast [N-(3',4'-dimethoxycinnamoyl)-anthranilic acid] and its analogs in yeast Saccharomyces cerevisiae.

Biological synthesis of therapeutic drugs beneficial for human health using microbes offers an alternative production strategy to the methods that are commonly employed such as direct extraction from source organisms or chemical synthesis. In this study, we evaluated the potential for yeast (Saccharomyces cerevisiae) to be used as a catalyst for the synthesis of tranilast and various tranilast analogs (cinnamoyl anthranilates). Several studies have demonstrated that these phenolic amides have antioxidant properties and potential therapeutic benefits including antiinflammatory, antiproliferative, and antigenotoxic effects.

Comparative genome-scale metabolic reconstruction and flux balance analysis of multiple Staphylococcus aureus genomes identify novel antimicrobial drug targets.

Mortality due to multidrug-resistant Staphylococcus aureus infection is predicted to surpass that of human immunodeficiency virus/AIDS in the United States. Despite the various treatment options for S. aureus infections, it remains a major hospital- and community-acquired opportunistic pathogen.

Induction of multiple pleiotropic drug resistance genes in yeast engineered to produce an increased level of anti-malarial drug precursor, artemisinic acid.

Background: Due to the global occurrence of multi-drug-resistant malarial parasites (Plasmodium falciparum), the anti-malarial drug most effective against malaria is artemisinin, a natural product (sesquiterpene lactone endoperoxide) extracted from sweet wormwood (Artemisia annua). However, artemisinin is in short supply and unaffordable to most malaria patients. Artemisinin can be semi-synthesized from its precursor artemisinic acid, which can be synthesized from simple sugars using microorganisms genetically engineered with genes from A.