Stick or twist? Career decision-making during contractual uncertainty for NHS junior doctors

OBJECTIVES: To examine the extent, and nature, of impact on junior doctors' career decisions, of a proposed new contract and the uncertainty surrounding it. DESIGN: Mixed methods. Online survey exploring: doctors' future training intentions; their preferred specialty training (ST) programmes; whether they intended to proceed immediately to ST; and other plans. Linked qualitative interviews to explore more fully how and why decisions were affected. SETTING: Doctors (F2s) in second year of Foundation School (FS) Programmes in England. PARTICIPANTS: Invitations sent by FSs. Open to all F2s November 2015-February 2016. All FSs represented. Survey completed by 816 F2s. Sample characteristics broadly similar to national F2 cohort. MAIN OUTCOME MEASURES: Proportions of doctors intending to proceed to ST posts in the UK, to defer or to exit UK medicine. Proportion of doctors indicating changes in training and career plans as a result of the contract and/or resulting uncertainty. Distribution of changes across training programmes. Explanations of these intentions from interviews and free text comments. RESULTS: Among the responding junior doctors, 20% indicated that issues related to the contract had prompted them to switch specialty and a further 20% had become uncertain about switching specialty. Switching specialty choice was more prevalent among those now choosing a community-based, rather than hospital-based specialty. 30% selecting general practice had switched choice because of the new contract. Interview data suggests that doctors felt they had become less valued or appreciated in the National Health Service and in society more broadly. CONCLUSIONS: Doctors reported that contract-related issues have affected their career plans. The most notable effect is a move away from acute to community-based specialities, with the former perceived as more negatively affected by the proposed changes. It is concerning that young doctors feel undervalued, and this requires further investigation

How Does a Photocatalytic Antimicrobial Coating Affect Environmental Bioburden in Hospitals?

BACKGROUND The healthcare environment is recognized as a source for healthcare-acquired infection. Because cleaning practices are often erratic and always intermittent, we hypothesize that continuously antimicrobial surfaces offer superior control of surface bioburden. OBJECTIVE To evaluate the impact of a photocatalytic antimicrobial coating at near-patient, high-touch sites in a hospital ward. SETTING The study took place in 2 acute-care wards in a large acute-care hospital. METHODS A titanium dioxide-based photocatalytic coating was sprayed onto 6 surfaces in a 4-bed bay in a ward and compared under normal illumination against the same surfaces in an untreated ward: right and left bed rails, bed control, bedside locker, overbed table, and bed footboard. Using standardized methods, the overall microbial burden and presence of an indicator pathogen (Staphylococcus aureus) were assessed biweekly for 12 weeks. RESULTS Treated surfaces demonstrated significantly lower microbial burden than control sites, and the difference increased between treated and untreated surfaces during the study. Hygiene failures (>2.5 colony-forming units [CFU]/cm2) increased 2.6% per day for control surfaces (odds ratio [OR], 1.026; 95% confidence interval [CI], 1.009-1.043; P=.003) but declined 2.5% per day for treated surfaces (OR, 0.95; 95% CI, 0.925-0.977;

Binary solvent system used to fabricate fully annealing-free perovskite solar cells

High temperature post-deposition annealing of hybrid lead halide perovskite thin films—typically lasting at least 10 min—dramatically limits the maximum roll-to-roll coating speed, which determines solar module manufacturing costs. While several approaches for “annealing-free” perovskite solar cells (PSCs) have been demonstrated, many are of limited feasibility for scalable fabrication. Here, this work has solvent-engineered a high vapor pressure solvent mixture of 2-methoxy ethanol and tetrahydrofuran to deposit highly crystalline perovskite thin-films at room temperature using gas-quenching to remove the volatile solvents. Using this approach, this work demonstrates p-i-n devices with an annealing-free MAPbI3 perovskite layer achieving stabilized power conversion efficiencies (PCEs) of up to 18.0%, compared to 18.4% for devices containing an annealed perovskite layer. This work then explores the deposition of self-assembled molecules as the hole-transporting layer without annealing. This work finally combines the methods to create fully annealing-free devices having stabilized PCEs of up to 17.1%. This represents the state-of-the-art for annealing-free fabrication of PSCs with a process fully compatible with roll-to-roll manufacture

Human and mouse essentiality screens as a resource for disease gene discovery

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery. Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma

Funder: Galderma; doi: http://dx.doi.org/10.13039/501100009754Funder: NIHR-BRC Cambridge core grantFunder: National Institute for Health Research; doi: http://dx.doi.org/10.13039/501100000272Funder: NHS EnglandAbstract: T-cell non-Hodgkin’s lymphomas develop following transformation of tissue resident T-cells. We performed a meta-analysis of whole exome sequencing data from 403 patients with eight subtypes of T-cell non-Hodgkin’s lymphoma to identify mutational signatures and associated recurrent gene mutations. Signature 1, indicative of age-related deamination, was prevalent across all T-cell lymphomas, reflecting the derivation of these malignancies from memory T-cells. Adult T-cell leukemia-lymphoma was specifically associated with signature 17, which was found to correlate with the IRF4 K59R mutation that is exclusive to Adult T-cell leukemia-lymphoma. Signature 7, implicating UV exposure was uniquely identified in cutaneous T-cell lymphoma (CTCL), contributing 52% of the mutational burden in mycosis fungoides and 23% in Sezary syndrome. Importantly this UV signature was observed in CD4 + T-cells isolated from the blood of Sezary syndrome patients suggesting extensive re-circulation of these T-cells through skin and blood. Analysis of non-Hodgkin’s T-cell lymphoma cases submitted to the national 100,000 WGS project confirmed that signature 7 was only identified in CTCL strongly implicating UV radiation in the pathogenesis of cutaneous T-cell lymphoma

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Transforming Sentiment: Adam Smith, Sentiment and Nation in Eighteenth-Century Transatlantic Literature

This thesis addresses points of connection among sentimental texts of the long eighteenth century that have previously been read as inhabiting distinct national literary traditions. Transforming Sentiment brings together the works of Samuel Richardson, Laurence Sterne, Sarah Robinson Scott, Charles Brockden Brown, Jane Austen, James Fenimore Cooper and Olaudah Equiano in order to demonstrate how seemingly disparate texts can be productively read to destabilize homogenous nationalist literary histories. Transforming Sentiment argues that these British and American sentimental authors can be understood and linked together in light of theories of sympathy and disinterestedness articulated in Adam Smith’s Theory of Moral Sentiments (1759) and specifically embodied by his figure of the impartial spectator. However, these theories resist being confined within national boundaries, and, consequently, these texts may be newly read as part of a transatlantic exchange, an exchange that alters the way we read sentimental texts: not as ineffective effusions of feeling but as possible alternate histories with transcultural potential. This thesis demonstrates how these authors adapt and interrogate the figure of the impartial spectator to think about the individual and the nation’s relationship to the other—from questioning imperial conquest, through models of benevolent paternalism, to more cosmopolitan views of global citizenship. By situating these texts within a transatlantic context, this thesis reveals the internal tensions within these authors’ texts that stem from an awareness of their global membership. It also demonstrates how this transatlantic intellectual exchange shapes the way these authors think about identity, the scope of moral obligation, and politics of empire. Transforming Sentiment argues that these authors share a collective discourse of sentiment that helps them reimagine traditional hierarchies of power and reductive social categories —for instance, these texts question the divisions between those who are recognized by the state as political participants with legal rights from those who are not. However, they mould the concepts of sympathy and disinterestedness to promote social reform according to the needs of their historical moment. By adapting Smith’s sentimental theories, these authors question constructions of nation and embrace the potential for a global theory of morality that the transatlantic offers

Jane Austen: second impressions

Bibliography: p. 154-16