Ethical and professional issues: Reflections on course evolution, innovation and student engagement.

At INSPIRE 2013 we outlined our efforts to develop a core first year undergraduate course entitled ‘Computing Technology in Society’. A primary course objective is to demonstrate the potential impact that ever more complex, interconnected digital systems may have on the both the individual and on society in general. This provides the backdrop against which we endeavour to foster an ethos in which students are encouraged to establish a personal ethical position in relation to the application and deployment of digital systems. Here we reflect on further progress in developing this course with particular reference to ongoing curriculum development, student evaluation and, most crucially, student engagement. Additionally, we outline developments relating to our integration of technologies into the educational experience. We draw on our experience with the CTIS course to consider broader ramifications of technology infusion, particularly in relation to increased VLE integration and the streaming/recording of lectures.n/

The influence of accurate attenuation correction on quantitative gamma camera imaging

Gamma camera systems are used in a variety of diagnostic applications to image and in some cases measure, the physiological uptake of a radioactive tracer within the body. A number of factors, particularly attenuation and scatter of photons within the body tissues can cause degradation of image quality and inaccuracies in the measurement of tracer uptake. Single photon emission tomography (SPECT) systems which incorporate an xray computed tomography (CT) facility have enabled accurate transmission images of the patient to be obtained. These ‘attenuation maps’ can be used to correct the SPECT images for the effects of attenuation. The aim of this project was to investigate the use of an x-ray CT based attenuation correction (AC) system in SPECT gamma camera imaging. The use of AC with other physical parameters of the imaging process including scatter was firstly examined in order to determine the optimum imaging parameters required to maximise image quality. The influence of attenuation, scatter and other imaging parameters on the accuracy of absolute and relative quantitative measurements was then investigated. The methodology involved using the GE Millenium Hawkeye gamma camera system to obtain images of a range of phantoms filled with various concentrations of radioactivity; from simple point sources to phantoms which simulate organs of the body. An attempt was made to establish SPECT sensitivity values that would allow accurate determination of activity in a region of interest. These sensitivity values were applied to all subsequent measurements and a measure made of quantitative accuracy. The results showed that the sensitivity value used for quantitative SPECT measurements must reflect the reconstruction method and corrections used in the acquisition. Attenuation correction proved to be more significant than scatter correction in quantitative accuracy, with activity results being within 30% of expected values in all cases where AC was used

Lst4, the yeast Fnip1/2 orthologue, is a DENN-family protein.

The folliculin/Fnip complex has been demonstrated to play a crucial role in the mechanisms underlying Birt-Hogg-Dubé (BHD) syndrome, a rare inherited cancer syndrome. Lst4 has been previously proposed to be the Fnip1/2 orthologue in yeast and therefore a member of the DENN family. In order to confirm this, we solved the crystal structure of the N-terminal region of Lst4 from Kluyveromyces lactis and show it contains a longin domain, the first domain of the full DENN module. Furthermore, we demonstrate that Lst4 through its DENN domain interacts with Lst7, the yeast folliculin orthologue. Like its human counterpart, the Lst7/Lst4 complex relocates to the vacuolar membrane in response to nutrient starvation, most notably in carbon starvation. Finally, we express and purify the recombinant Lst7/Lst4 complex and show that it exists as a 1 : 1 heterodimer in solution. This work confirms the membership of Lst4 and the Fnip proteins in the DENN family, and provides a basis for using the Lst7/Lst4 complex to understand the molecular function of folliculin and its role in the pathogenesis of BHD syndrome.AP, BKB and RKN were supported by the Myrovlytis Trust. DBA was supported by a NHMRC CJ Martin Fellowship (APP1072476). LHW was supported by Medical Research Council (MRC) studentship, MR/J006580/1 and TPL by University College London. SD was supported by Fondation de France, La Ligue National contre le Cancer (Comité de Paris / Ile-de-France and Comité de l’Oise); TLB and NZ thank the University of Cambridge and The Wellcome Trust for facilities and support.This is the final version of the article. It was first available from Royal Society Publishing via http://dx.doi.org/10.1098/rsob.15017

Effects of aroma and taste, independently or in combination, on appetite sensation and subsequent food intake

Food flavour is important in appetite control. The effects of aroma and taste, independently or in combination, on appetite sensation and subsequent food intake, were studied. Twenty-six females (24 ± 4 years, 20.9 ± 1.9 kg⋅m-2) consumed, over 15 min period, one of four sample drinks as a preload, followed by an ad libitum consumption of a pasta meal (after 65 min). Sample drinks were: water (S1, 0 kcal), water with strawberry aroma (S2, 0 kcal), water with sucrose and citric acid (S3, 48 kcal) and water with strawberry aroma, sucrose and citric acid (S4, 48 kcal). Appetite sensation did not differ between the S1 (water), S2 (aroma) and S3 (taste) conditions. Compared with S1 (water), S2 (aroma) and S3 (taste), S4 (aroma + taste) suppressed hunger sensation over the 15 min sample drink consumption period (satiation) (p < 0.05). S4 (aroma + taste) further reduced hunger sensation (satiety) more than S1 at 5, 20 and 30 min after the drink was consumed (p < 0.05), more than S2 (aroma) at 5 and 20 min after the drink was consumed (p < 0.05), and more than S3 (taste) at 5 min after the drink was consumed (p < 0.05). Subsequent pasta energy intake did not vary between the sample drink conditions. S4 (aroma + taste) had the strongest perceived flavour. This study suggests that the combination of aroma and taste induced greater satiation and short-term satiety than the independent aroma or taste and water, potentially via increasing the perceived flavour intensity or by enhancing the perceived flavour quality and complexity as a result of aroma-taste cross-modal perception

House Price Volatility and the Housing Ladder

This paper investigates the effects of housing price risk on housing choices over the lifecycle. Housing price risk can be substantial but, unlike other risky assets which people can avoid, the fact that most people will eventually own their home creates an insurance demand for housing assets early in life. Our contribution is to focus on the importance of home ownership and housing wealth as a hedge against future house price risk for individuals moving up the ladder - people living in places with higher housing price risk should own their first home at a younger age, should live in larger homes, and should be less likely to refinance. These predictions are tested and shown to hold using panel data from the United States and Great Britain

Adjusting for unmeasured confounding in nonrandomized longitudinal studies: a methodological review

OBJECTIVE: Motivated by recent calls to use electronic health records for research, we reviewed the application and development of methods for addressing the bias from unmeasured confounding in longitudinal data. DESIGN: Methodological review of existing literature SETTING: We searched MEDLINE and EMBASE for articles addressing the threat to causal inference from unmeasured confounding in nonrandomised longitudinal health data through quasi-experimental analysis. RESULTS: Among the 121 studies included for review, 84 used instrumental variable analysis (IVA), of which 36 used lagged or historical instruments. Difference-in-differences (DiD) and fixed effects (FE) models were found in 29 studies. Five of these combined IVA with DiD or FE to try to mitigate for time-dependent confounding. Other less frequently used methods included prior event rate ratio adjustment, regression discontinuity nested within pre-post studies, propensity score calibration, perturbation analysis and negative control outcomes. CONCLUSIONS: Well-established econometric methods such as DiD and IVA are commonly used to address unmeasured confounding in non-randomised, longitudinal studies, but researchers often fail to take full advantage of available longitudinal information. A range of promising new methods have been developed, but further studies are needed to understand their relative performance in different contexts before they can be recommended for widespread use

Evolution and host-specific adaptation of <i>Pseudomonas aeruginosa</i>.

The major human bacterial pathogen Pseudomonas aeruginosa causes multidrug-resistant infections in people with underlying immunodeficiencies or structural lung diseases such as cystic fibrosis (CF). We show that a few environmental isolates, driven by horizontal gene acquisition, have become dominant epidemic clones that have sequentially emerged and spread through global transmission networks over the past 200 years. These clones demonstrate varying intrinsic propensities for infecting CF or non-CF individuals (linked to specific transcriptional changes enabling survival within macrophages); have undergone multiple rounds of convergent, host-specific adaptation; and have eventually lost their ability to transmit between different patient groups. Our findings thus explain the pathogenic evolution of P. aeruginosa and highlight the importance of global surveillance and cross-infection prevention in averting the emergence of future epidemic clones

Health, education, and social care provision after diagnosis of childhood visual disability

Aim: To investigate the health, education, and social care provision for children newly diagnosed with visual disability.Method: This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vi-sion. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision.Results: BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2p < 0.001), or had an EHCP (11% vs 7%, χ2p < 0 . 01).Interpretation: Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication