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We provide evidence of the impact of the COVID-19 pandemic on racial hate crime in England and Wales. Using various data sources, including unique data collected through Freedom of Information (FOI) requests from UK police forces, a difference-in-difference and event study approaches, we find that racial hate crime against East Asians increased by 70-100%, beginning in early February and persisted until November 2020. This effect was greatest in weeks leading up to the first national lockdown in the UK. The shock was then lower during lockdown, before increasing again in the summer 2020. We present evidence that hate crime increased as COVID-19 cases in China increased and following announcements from the government signalling that China or Chinese individuals posed a public health risk to the UK. This indicates that protectionism played an important role in the observed hate crime spike. The hate crime shock was also positively correlated with the salience of the national lockdown and government policies restricting certain freedoms. The effect was driven largely by changes in London. This suggests that retaliation further contributed to the rise in hate crime.

In May 2018, Scotland introduced a minimum unit price on alcohol. We examine the impact of this policy on traffic fatalities and drunk driving accidents. Using administrative data on the universe of vehicle collisions in Britain and a range of quasi-experimental modeling approaches, we do not find that the policy had an effect on road crash deaths and drunk driving collisions. The results are robust to several sensitivity exercises. There is no evidence of effect heterogeneity by income and other predictors of alcohol consumption or cross-border effects. A brief discussion of the policy implications of our findings is provided.

We provide evidence of the impact of the COVID-19 pandemic on racial hate crime in England and Wales. Using various data sources, including unique data collected through Freedom of Information (FOI) requests from UK police forces, a difference-in-difference and event study approaches, we find that racial hate crime against East Asians increased by 70-100%, beginning in early February and persisted until November 2020. This increase was greatest in the weeks leading up to the first national lockdown in the UK. The shock was then lower during lockdown, before increasing again in the summer 2020. We present evidence that hate crime increased as COVID-19 cases in China increased and following announcements from the government signalling that China or Chinese individuals posed a public health risk to the UK. This indicates that protectionism played an important role in the observed hate crime spike. The hate crime shock was also positively correlated with the salience of the national lockdown and government policies restricting certain freedoms. The effect was driven largely by changes in London. This suggests that retaliation for lockdown contributed to the rise in hate crime.

A partir de uma perspectiva interdiscursiva e interdisciplinar, este trabalho aborda diferentes representacoes com as quais o povo mapuche do Gulumapu construiu seus processos de diferenciacao cultural e territorial em tensao com o Estado nacional chileno. Atraves de discursos heterogeneos - historico, literario, midiatico, testemunhal e das organizacoes politicas - , expressa-se um processo que parte de uma visao unitaria ancestral para assumir estrategicamente concepcoes modernas, tipicas de novos cenarios geopoliticos e supranacionais, como as de Estado e / ou nacao. Conclui-se que este processo transversaliza seus discursos, os quais, em conjunto, representam um imaginario coletivo compartilhado que relaciona a nocao ancestral- Wallmapu - com a visao moderna e / ou Estado mapuche.

From an interdiscoursive and interdisciplinary perspective, this paper explores different representations with which the Mapuche People of the Gulumapu constructed their processes of cultural and territorial differentiation in tension with the Chilean Nation State. Through heterogeneous discourses -historical, literary, media, testimonial and of political organizations-, a process is expressed that moves from an ancestral unitary vision to strategically assumed modern conceptions, typical of new geopolitical and supranational scenarios, such as those of the State and/or nation. It is concluded that this process mainstream their discourses, which as a whole represent a shared collective imaginary that relates the ancestral notion -Wallmapu- with the modern vision -nation and/or Mapuche State.

Background Chronic inflammation caused by ulcerative colitis (UC) causes a pro-neoplastic drive in the inflamed colon, leading to a markedly greater risk of invasive malignancy compared to the general population. Despite surveillance protocols, 50% of cases proceed to cancer before neoplasia is detected. The Enhanced Neoplasia Detection and Cancer Prevention in Chronic Colitis (ENDCaP-C) trial is an observational multi-centre test accuracy study to ascertain the role of molecular markers in improving the detection of dysplasia. We aimed to validate previously identified biomarkers of neoplasia in a retrospective cohort and create predictive models for later validation in a prospective cohort. Methods A retrospective analysis using bisulphite pyrosequencing of an 11 marker panel (SFRP1, SFRP2, SRP4, SRP5, WIF1, TUBB6, SOX7, APC1A, APC2, MINT1, RUNX3) in samples from 35 patients with cancer, 78 with dysplasia and 343 without neoplasia undergoing surveillance for UC associated neoplasia across 6 medical centres. Predictive models for UC associated cancer/dysplasia were created in the setting of neoplastic and non-neoplastic mucosa. Findings For neoplastic mucosa a five marker panel (SFRP2, SFRP4, WIF1, APC1A, APC2) was accurate in detecting pre-cancerous and invasive neoplasia (AUC = 0.83; 95% CI: 0.79, 0.88), and dysplasia (AUC = 0.88; (0.84, 0.91). For non-neoplastic mucosa a four marker panel (APC1A, SFRP4, SFRP5, SOX7) had modest accuracy (AUC = 0.68; 95% CI: 0.62,0.73) in predicting associated bowel neoplasia through the methylation signature of distant non-neoplastic colonic mucosa. Interpretation This multiplex methylation marker panel is accurate in the detection of ulcerative colitis associated dysplasia and neoplasia and is currently being validated in a prospective clinical trial. Funding The ENDCAP-C study was funded by the National Institute for Health Research Efficacy and Mechanism Evaluation (EME) Programme (11/100/29).

Reducing drink drive limits is generally regarded an effective strategy to save lives on the road. Using several new administrative data sources, we evaluate the effect of a stricter limit introduced in Scotland in 2014. This reduction had no effect on drink driving and road collisions. Estimates from a supply-of-offenses function suggests that the reform did not have much ex-ante scope for sizeable effects. The unavailability of cheaper alternative means of transportation and weak law enforcement seem to have been the main channels behind the lack of an impact. We find no externality on a wide range of domains, from alcohol consumption to criminal activities other than drink driving.

BACKGROUND Youper is a widely used, commercially available mobile app that uses artificial intelligence therapy for the treatment of anxiety and depression. OBJECTIVE Our study examined the acceptability and effectiveness of Youper. Further, we tested the cumulative regulation hypothesis, which posits that cumulative emotion regulation successes with repeated intervention engagement will predict longer-term anxiety and depression symptom reduction. METHODS We examined data from paying Youper users (N=4517) who allowed their data to be used for research. To characterize the acceptability of Youper, we asked users to rate the app on a 5-star scale and measured retention statistics for users’ first 4 weeks of subscription. To examine effectiveness, we examined longitudinal measures of anxiety and depression symptoms. To test the cumulative regulation hypothesis, we used the proportion of successful emotion regulation attempts to predict symptom reduction. RESULTS Youper users rated the app highly (mean 4.36 stars, SD 0.84), and 42.66% (1927/4517) of users were retained by week 4. Symptoms decreased in the first 2 weeks of app use (anxiety: d=0.57; depression: d=0.46). Anxiety improvements were maintained in the subsequent 2 weeks, but depression symptoms increased slightly with a very small effect size (d=0.05). A higher proportion of successful emotion regulation attempts significantly predicted greater anxiety and depression symptom reduction. CONCLUSIONS Youper is a low-cost, completely self-guided treatment that is accessible to users who may not otherwise access mental health care. Our findings demonstrate the acceptability and effectiveness of Youper as a treatment for anxiety and depression symptoms and support continued study of Youper in a randomized clinical trial.

Au cours des trois dernières décennies, plusieurs modèles théoriques de l’homicide sexuel ont été proposés. Ces modèles ont suggéré qu’il existe une diversité de facteurs associés à la commission d’un ou de plusieurs homicides sexuels, notamment des facteurs développementaux, psychologiques et de l’événement criminel et ont permis de proposer un profil des individus ayant commis un homicide sexuel. Cependant, aucun de ces profils n’a intégré l’ensemble de ces facteurs en un tout cohérent. De plus, ces modèles et profils, à l’exception du modèle proposé par des chercheurs associés au Federal Bureau of Investigation, ont été réalisés à partir d’échantillons d’individus ayant commis un seul homicide sexuel. En conséquence, bien que ces modèles et profils proposent une explication de l’émergence de ces comportements, ils ne permettent pas d’expliquer dans quelles circonstances ceux-ci se répètent et prennent fin. Étant donné que ces modèles et profils n’ont pas pris en considération les caractéristiques du parcours de vie de l’individu après la commission du premier homicide sexuel, ceux-ci n’intègrent pas de paramètres post-homicides, tels que les paramètres de l’enquête criminelle. En conséquence, il existe actuellement peu de certitudes concernant les caractéristiques du profil des individus pouvant constituer des facteurs permettant potentiellement d’expliquer pourquoi certains individus commettront une série d’homicides sexuels tandis que d’autres n’en commettront qu’un. L’objectif principal de cette thèse est d’identifier les caractéristiques distinctives des individus ayant commis une série d’homicides sexuels, afin de proposer des profils d’individus sériels et non-sériels. Afin d’atteindre cet objectif, une série d’études comparatives entre des individus ayant commis des homicides sexuels en série (HSS; n = 33) et des individus ayant commis un seul homicide sexuel (HS; n = 87) ont été réalisées. Les résultats de cette étude mettent en évidence que les caractéristiques qui distinguent les sériels des non-sériels ne se limitent pas à des facteurs individuels ou à la façon dont les individus commettent leur crime, mais aussi à l’échec des intervenants de l’enquête criminelle à appliquer les pratiques considérées comme étant indispensables à la résolution rapide d’un homicide. D’autre part, les résultats de cette étude mettent en évidence qu’il existe deux principaux profils d’individus ayant commis un homicide sexuel, celui des HSS et celle des HS. Finalement, les résultats de cette étude ont servi de fondations au développement d’un modèle conceptuel théorique de l’homicide sexuel sériel et non-sériel qui permet d’expliquer dans quelles circonstances le phénomène semblerait émerger, se répéter et prendre fin., Over the last three decades, many theoretical models of sexual homicide have been proposed, which have made it possible to propose a profile of individuals. Although these models and profiles have suggested associations between the commission of one or more sexual homicides and a wide variety of factors—notably developmental, psychological, and crime-phase—none has produced a unified vision of sexual homicide that takes into account all factors. Moreover, these models and profiles, with the exception of that of the US Federal Bureau of Investigation, have been based on samples of individuals having committed a single homicide. As a result, although they propose explanations of the emergence of sexual homicide, current models and profiles are silent on the determinants of its repetition and cessation. Additionally, these models and profiles do not address post-homicide parameters, such as those related to the criminal investigation, since they do not take into account the sexual murderer’s life course following the commission of the homicide. For all these reasons, considerable uncertainty remains about why some individuals commit a series of sexual homicides while others commit only one. The principal objective of this thesis’s research was therefore to identify the distinctive characteristics of individuals having committed a series of sexual homicides, in order to proposed profiled of serial and nonserial sexual murderers. To this end, comparative analyses of serial sexual murderers (HSSs; n = 33) and nonserial sexual murderers (HSs n = 87) were conducted. The results indicate that the two groups of participants in this sample can be distinguished not only on individual factors and the manner in which the homicide was committed, but also on the failure of criminal investigators to apply best practices and rapidly resolve the homicides. Finally, this thesis’ research establishes a foundation for the development of theoretical models of serial and nonserial sexual homicide that explain the circumstances responsible for the emergence, repetition, and cessation of this phenomenon.

PurposeTo compare an individual’s Personal Performance in Mammographic Screening (PERFORMS) score with their Breast Screening Information System (BSIS) real-life performance data and determine which parameters in the PERFORMS scheme offer the best reflection of BSIS real-life performance metrics.Materials and MethodsIn this retrospective study, the BSIS real-life performance metrics of individual readers (n = 452) in the National Health Service Breast Screening Program (NHSBSP) in England were compared with performance in the test set–based assessment scheme over a 3-year period from 2013 to 2016. Cancer detection rate (CDR), recall rate, and positive predictive value (PPV) were calculated for each reader, for both real-life screening and the PERFORMS test. For each metric, real-life and test set versions were compared using a Pearson correlation. The real-life CDR, recall rate, and PPV of outliers were compared against other readers (nonoutliers) using analysis of variance.ResultsBSIS real-life CDRs, recall rates, and PPVs showed positive correlations with the equivalent PERFORMS measures (P < .001, P = .002, and P < .001, respectively). The mean real-life CDR of PERFORMS outliers was 7.2 per 1000 women screened and was significantly lower than other readers (nonoutliers) where the real-life CDR was 7.9 (P = .002). The mean real-life screening PPV of PERFORMS outliers was 0.14% and was significantly lower than the nonoutlier group who had a mean PPV of 0.17% (P = .006).ConclusionThe use of test set–based assessment schemes in a breast screening program has the potential to predict and identify poor performance in real life.

In this paper we examine the impact of a tailored health warning on health outcomes. We exploit the design of a household panel survey that provided feedback to participants on their blood-pressure levels as a quasi-experiment. We find that many participants who were told their blood-pressure was high went on to get a formal diagnosis of hypertension from a medical practitioner. The effect of getting a formal hypertension diagnosis was to reduce the incidence of smoking and improve the quality of diets. However, we do not find changes in monthly alcohol spending. The behavioural changes (plus any prescribed medications) were large enough to reduce the incidence of cardiovascular disease.

We provide causal evidence of the impact of the Brexit referendum vote on hate crime in the United Kingdom (UK). Using various data sources, including unique data collected from the UK Police Forces by Freedom of Information (FOI) requests, and various estimation methods (difference-in-differences, event-study analysis and synthetic control methods), we find that the Brexit referendum led to an increase in hate crime by around 15-25%. This effect was concentrated in the first quarter after the referendum and was larger in areas that voted to leave the European Union (EU). We also provide evidence against the hypotheses that this was due to victims' greater willingness to report crimes or due to changes in police behaviour and perceptions of the victims. We also present suggestive evidence that the media and social media played a small but significant role in the increase in hate crime.

We investigate whether short-term everyday stressors leads to unhealthier dietary choices among low socioeconomic status mothers. We propose a novel stress protocol that aims to mimic everyday stressors experienced by this population, involving time and financial pressure. We evaluate the impact of stress on immediate and planned food choices, comparing a group exposed to our stress protocol relative to a control group. Immediate consumption is measured with in-laboratory consumption of low calorie and high calorie snacks; planned consumption is measured with an incentivized food shopping task. The stressfulness of the stress protocol is evaluated using subjective assessments, as well as physiological measurements (heart rate and salivary cortisol levels). We find no evidence of an effect of stress on the nutritional content of immediate or planned food consumption, thus no support for the hypothesis that everyday stressors are a likely explanation for unhealthy food choices.

We examine the impact of financial distress conditions at the individual firm level, the operating industry level, and economy-wide, on the stock price reaction to divestment announcements. This allows us to isolate distinct fire sale and financing theoretical explanations of asset divestments. We find that abnormal returns are significantly lower when firms divest assets during periods of industry-wide distress. During these periods the natural buyers of the divested assets are likely to have liquidity constraints, and so selling firms receive a lower price (Shleifer and Vishny, 1992). Fire sale effects from divestments are driven by financially constrained firms, firms selling core assets, small firms, and increase with deal size. We find some support for the financing explanation of the stock price response to divestments during periods of overlapping firm-level and economy-wide financial distress conditions, suggesting that divesting assets reduce the expected value of bankruptcy costs for selling firms under these conditions.

Background and aims Ulcerative colitis (UC) is associated with a higher background risk of dysplasia and/or neoplasia due to chronic inflammation. There exist few biomarkers for identification of patients with dysplasia, and targeted biopsies in this group of patients are inaccurate in reliably identifying dysplasia. We aimed to examine the epigenome of UC dysplasia and to identify and validate potential biomarkers Methods Colonic samples from patients with UC-associated dysplasia or neoplasia underwent epigenome-wide analysis on the Illumina 450K methylation array. Markers were validated by bisulphite pyrosequencing on a secondary validation cohort and accuracy calculated using logistic regression and receiver-operator curves. Results Twelve samples from 4 patients underwent methylation array analysis and 6 markers (GNG7, VAV3, KIF5C, PIK3R5, TUBB6, and ZNF583) were taken forward for secondary validation on a cohort of 71 colonic biopsy samples consisting of normal uninflamed mucosa from control patients, acute and chronic colitis, “field” mucosa in patients with dysplasia/neoplasia, dysplasia, and neoplasia. Methylation in the beta-tubulin TUBB6 correlated with the presence of dysplasia (P < 0.0001) and accurately discriminated between dysplasia and nondysplastic tissue, even in the apparently normal field mucosa downstream from dysplastic lesions (AUC 0.84, 95% CI 0.81–0.87). Conclusions Methylation in TUBB6 is a potential biomarker for UC- associated dysplasia. Further validation is needed and is ongoing as part of the ENDCAP-C study.

Background Youper is a widely used, commercially available mobile app that uses artificial intelligence therapy for the treatment of anxiety and depression. Objective Our study examined the acceptability and effectiveness of Youper. Further, we tested the cumulative regulation hypothesis, which posits that cumulative emotion regulation successes with repeated intervention engagement will predict longer-term anxiety and depression symptom reduction. Methods We examined data from paying Youper users (N=4517) who allowed their data to be used for research. To characterize the acceptability of Youper, we asked users to rate the app on a 5-star scale and measured retention statistics for users’ first 4 weeks of subscription. To examine effectiveness, we examined longitudinal measures of anxiety and depression symptoms. To test the cumulative regulation hypothesis, we used the proportion of successful emotion regulation attempts to predict symptom reduction. Results Youper users rated the app highly (mean 4.36 stars, SD 0.84), and 42.66% (1927/4517) of users were retained by week 4. Symptoms decreased in the first 2 weeks of app use (anxiety: d=0.57; depression: d=0.46). Anxiety improvements were maintained in the subsequent 2 weeks, but depression symptoms increased slightly with a very small effect size (d=0.05). A higher proportion of successful emotion regulation attempts significantly predicted greater anxiety and depression symptom reduction. Conclusions Youper is a low-cost, completely self-guided treatment that is accessible to users who may not otherwise access mental health care. Our findings demonstrate the acceptability and effectiveness of Youper as a treatment for anxiety and depression symptoms and support continued study of Youper in a randomized clinical trial.

Supplemental Digital Content is available in the text, Objective: To investigate differences in methylation between patients with nondysplastic Barrett esophagus who progress to invasive adenocarcinoma and those who do not. Background: Identifying patients with nondysplastic Barrett esophagus who progress to invasive adenocarcinoma remains a challenge. Previous studies have demonstrated the potential utility of epigenetic markers for identifying this group. Methods: A whole genome methylation interrogation using the Illumina HumanMethylation 450 array of patients with nondysplastic Barrett esophagus who either develop adenocarcinoma or remain static, with validation of findings by bisulfite pyrosequencing. Results: In all, 12 patients with “progressive” versus 12 with “nonprogressive” nondysplastic Barrett esophagus were analyzed via methylation array. Forty-four methylation markers were identified that may be able to discriminate between nondysplastic Barrett esophagus that either progress to adenocarcinoma or remain static. Hypomethylation of the recently identified tumor suppressor OR3A4 (probe cg09890332) validated in a separate cohort of samples (median methylation in progressors 67.8% vs 96.7% in nonprogressors; P = 0.0001, z = 3.85, Wilcoxon rank-sum test) and was associated with the progression to adenocarcinoma. There were no differences in copy number between the 2 groups, but a global trend towards hypomethylation in the progressor group was observed. Conclusion: Hypomethylation of OR3A4 has the ability to risk stratify the patient with nondysplastic Barrett esophagus and may form the basis of a future surveillance program.

This paper tests an intervention aimed at facilitating (cognitively) the adoption of healthy dietary habits. We provide easy-to-understand information about the risks of developing diabetes or heart diseases and give easy-to-follow dietary recommendations to minimize these risks. We implement two variations, one consisting of generic information, the other consisting of information tailored to the individual, the latter resembling newly developed on-line health assessment tools. On top of the information treatment, we implement a second experimental variation nudging people into spending more time thinking about their dietary choices. We find evidence that the information intervention leads to healthier choices in the short run, but mostly in the generic treatment. Surprisingly, we find that people are on average pessimistic about their health, and therefore receive good news on average when the information is tailored to them. We find no evidence that increasing the time available to make choices leads to healthier choices, and find no evidence of long-term changes in habits. These results do not support a bounded rationality explanation for poor dietary choices.

We present and evaluate a new incentive-based tool to measure people’s dietarychoices in a low-cost and time effective manner. Respondents are asked to allocatea fixed monetary budget across a choice of around a hundred grocery items with theprospect of receiving these items with some probability delivered to their home by areal supermarket. The tool has the advantage of offering a broad coverage of dietarychoices, allows inference of macro-nutrients and calorie, and allows the researcher to fixthe choice set participants can choose from. We compare the information derived fromour incentivized tool, and compare it to alternative low-cost ways of measuring dietaryintake, namely the food frequency questionnaire and a one-shot version of the 24hour dietary recall, which are both based on self-reports. We invited 255 low incomeparticipants to our laboratory and collected measures using these three alternativetools. We compare the calorie intake indicators derived from each tool with a numberof biometric measures for each subject, namely weight, body-mass-index (BMI) andwaist size. The results show that the dietary information collected is only weaklycorrelated across the three tools. We also find that only the calorie intake measure fromour incentivized tool is positively and significantly related to each of these biometricindicators. By contrast, we find no significant correlations for either of the two measuresbased on self-reports. We therefore argue that our tool may be useful for researchconducted with limited time and budget.

This paper examines the effect of education on the timing of fertility. First,we use an institutional rule that led to women obtaining qualifications due to theirmonth of birth (Easter Leaving Rule). Second, we exploit a large expansion ofpost-compulsory schooling that occurred from the late 1980s to the early 1990s.This expansion resulted in the proportion of 18 year olds in full time educationrising from around 17% in 1985 to over 35% in the late 1990s. We find that neitherthe exogenous increase in qualifications as a result of the Easter Leaving Rule northe expansion in post-compulsory schooling led to a reduction in the probability ofhaving a child as a teenager. However, we do find that both sources of variation ineducation led to delays in having a child. There is no evidence that the mechanismdriving these findings are due to an incapacitation effect. Instead the results pointto both a direct human capital effect and an improvement in labour market oppor-tunities as a result of holding qualifications.

Background:\ud Highly sensitive and specific urine-based tests to detect either primary or recurrent bladder cancer have proved elusive to date. Our ever increasing knowledge of the genomic aberrations in bladder cancer should enable the development of such tests based on urinary DNA.\ud \ud Methods:\ud DNA was extracted from urine cell pellets and PCR used to amplify the regions of the TERT promoter and coding regions of FGFR3, PIK3CA, TP53, HRAS, KDM6A and RXRA which are frequently mutated in bladder cancer. The PCR products were barcoded, pooled and paired-end 2 x 250 bp sequencing performed on an Illumina MiSeq. Urinary DNA was analysed from 20 non-cancer controls, 120 primary bladder cancer patients (41 pTa, 40 pT1, 39 pT2+) and 91 bladder cancer patients post-TURBT (89 cancer-free).\ud \ud Results:\ud Despite the small quantities of DNA extracted from some urine cell pellets, 96% of the samples yielded mean read depths >500. Analysing only previously reported point mutations, TERT mutations were found in 55% of patients with bladder cancer (independent of stage), FGFR3 mutations in 30% of patients with bladder cancer, PIK3CA in 14% and TP53 mutations in 12% of patients with bladder cancer. Overall, these previously reported bladder cancer mutations were detected in 86 out of 122 bladder cancer patients (70% sensitivity) and in only 3 out of 109 patients with no detectable bladder cancer (97% specificity).\ud \ud Conclusion:\ud This simple, cost-effective approach could be used for the non-invasive surveillance of patients with non-muscle-invasive bladder cancers harbouring these mutations. The method has a low DNA input requirement and can detect low levels of mutant DNA in a large excess of normal DNA. These genes represent a minimal biomarker panel to which extra markers could be added to develop a highly sensitive diagnostic test for bladder cancer.

BackgroundHighly sensitive and specific urine-based tests to detect either primary or recurrent bladder cancer have proved elusive to date. Our ever increasing knowledge of the genomic aberrations in bladder cancer should enable the development of such tests based on urinary DNA.MethodsDNA was extracted from urine cell pellets and PCR used to amplify the regions of the TERT promoter and coding regions of FGFR3, PIK3CA, TP53, HRAS, KDM6A and RXRA which are frequently mutated in bladder cancer. The PCR products were barcoded, pooled and paired-end 2 x 250 bp sequencing performed on an Illumina MiSeq. Urinary DNA was analysed from 20 non-cancer controls, 120 primary bladder cancer patients (41 pTa, 40 pT1, 39 pT2+) and 91 bladder cancer patients post-TURBT (89 cancer-free).ResultsDespite the small quantities of DNA extracted from some urine cell pellets, 96% of the samples yielded mean read depths >500. Analysing only previously reported point mutations, TERT mutations were found in 55% of patients with bladder cancer (independent of stage), FGFR3 mutations in 30% of patients with bladder cancer, PIK3CA in 14% and TP53 mutations in 12% of patients with bladder cancer. Overall, these previously reported bladder cancer mutations were detected in 86 out of 122 bladder cancer patients (70% sensitivity) and in only 3 out of 109 patients with no detectable bladder cancer (97% specificity).ConclusionThis simple, cost-effective approach could be used for the non-invasive surveillance of patients with non-muscle-invasive bladder cancers harbouring these mutations. The method has a low DNA input requirement and can detect low levels of mutant DNA in a large excess of normal DNA. These genes represent a minimal biomarker panel to which extra markers could be added to develop a highly sensitive diagnostic test for bladder cancer.

SNAPPSâ Survey instrument for Natural history, Aetiology and Prevalence of Patellofemoral pain Studies. (DOCX 111Â kb)

Much is known about the effects and costs of sustained heavy drinking, such as the increased risk of chronic disease and injury to individuals, the damage to social relationships and the additional burden on public services (such as healthcare and policing). However, little is known about the economic and social effects of binge drinking. This brief, by Dr Jonathan James (University of Bath) and Professor Marco Francesconi (University of Essex) estimates the additional cost to the economy generated by binge drinking by examining its effects on Accident and Emergency (A&E) admissions, road accidents, arrests and the number of police officers on duty. This estimate is then used to assess the likely effectiveness of policies designed to discourage binge drinking and mitigate its effects and costs. The three potential policy interventions considered are minimum unit pricing, alcohol excise taxes and a higher minimum legal drinking age (MLDA).

We estimate the effect of binge drinking on accident and emergency attendances, road accidents, arrests, and the number of police officers on duty using a variety of unique data from Britain and a two-sample minimum distance estimation procedure. Our estimates, which reveal sizeable effects of bingeing on all outcomes, are then used to monetize the short-term externalities of binge drinking. We find that these externalities are on average £4.9 billion per year ($7 billion), about £80 for each man, woman, and child living in the UK. The price that internalizes this externality is equivalent to an additional 9p per alcoholic unit, implying a 20% increase with respect to the current average price.

We conduct a field experiment in 31 primary schools in England to test the effectiveness of different temporary incentive schemes, an individual based incentive scheme and a competitive scheme, on increasing the choice and consumption of fruit and vegetables at lunchtime. The individual scheme has a weak positive effect whereas all pupils respond to positively to the competitive scheme. For our sample of interest, the competitive scheme increases choice of fruit and vegetables by 33% and consumption of fruit and vegetables by 48%, twice and three times as much as the individual incentive scheme, respectively. The positive effects generally carry over to the week immediately following the treatment but we find little evidence of any effects six months later. Our results show that incentives can work, at least temporarily, to increase healthy eating but there are large differences in effectiveness between schemes and across demographics such as age and gender.

We estimate the effect of binge drinking on accident and emergency attendances, road accidents, arrests, and the number of police officers on duty using a variety of unique data from Britain and a two-sample minimum distance estimation procedure. Our estimates, which reveal sizeable effects of bingeing on all outcomes, are then used to monetize the short-term externalities of binge drinking. We find that these externalities are on average £4.9 billion per year ($7 billion), about £80 for each man, woman, and child living in the UK. The price that internalizes this externality is equivalent to an additional 9p per alcoholic unit, implying a 20% increase with respect to the current average price.

We conduct a field experiment in 31 primary schools in England to test the effectiveness of different temporary incentive schemes, a standard individual based incentive scheme and a competitive scheme, on increasing the choice and consumption of healthy items at lunchtime. The individual scheme has a weak positive effect that masks significantly differential effects by age whereas all students respond to positively to the competitive scheme. For our sample of interest, the competitive scheme increases choice of healthy items by 33% and consumption of healthy items by 48%, twice and three times as much as in the individual incentive scheme, respectively. The positive effects generally carry over to the week immediately following the treatment but we find little evidence of any effects six months later. Our results show that incentives can work, at least temporarily, to increase healthy eating but that there are large differences in effectiveness between schemes. Furthermore it is important to analyse things at the individual level as average effects appear to be masking significant heterogeneous effects that are predicted by the health literature.

Eculizumab, marketed as ‘Soliris’ by Alexion Pharmaceuticals Inc., is a humanised, Fc-engineered (low effector function), IgG2/4 hybrid monoclonal antibody that blocks the activity of human complement factor C5. This activity enables eculizumab to potently suppress the pro-inflammatory and cytolytic effects of the terminal complement system, which are key factors in the pathology of the rare haemolytic disease paroxysmal nocturnal haemoglobinuria (PNH). This antibody therapeutic has become an important example of a potential therapeutic molecule that was originally developed for a series of common inflammatory diseases (rheumatoid arthritis, lupus, etc.), but was repurposed with great success to become a first-in-class complement inhibitor in the rare disease space.

There is a growing interest from both academics and policy makers in the use of incentives to change health behaviours; especially of children.In October 2011, Michèle Belot (University of Edinburgh), Jonathan James (University of Bath) and Patrick Nolen (University of Essex) carried out a randomised controlled field experiment in 31 schools across England.The aim was to assess the effect of schemes that reward children with stickers, small toys and stationery for choosing fruit and vegetables at lunch time. Two incentive schemes (individual based and competition) were compared to a control group where no incentives were provided.The effects on choice and consumption were examined over the course of the four week intervention, immediately after the incentives were removed and six months later. In both incentive schemes pupils were given a sticker if they chose a fruit or vegetable at lunch time, or brought one in their packed lunch. Pupils in the individual treatment were given an additional reward on each Friday if they had collected four or more stickers over the week. In the competition scheme pupils were randomly assigned into groups of four, however the groups were only revealed at the end of the week and the pupil with the most stickers was given an additional reward.Although results differ by age, gender and socio-economic background, the research found that the incentives increased the choice and consumption of fruit and vegetables, particularly among the group who were previously identified as not regularly eating fruit and vegetables.

This study investigates the issue of self-selection of stakeholders into participation and collaboration in policy-relevant experiments. We document and test the implications of self-selection in the context of randomised policy experiment we conducted in primary schools in the UK. The main questions we ask are (1) is there evidence of selection on key observable characteristics likely to matter for the outcome of interest and (2) does selection matter for the estimates of treatment effects. The experimental work consists in testing the effects of an intervention aimed at encouraging children to make more healthy choices at lunch. We recruited schools through local authorities and randomised schools across two incentive treatments and a control group. We document the selection taking place both at the level of local authorities and at the school level. Overall we find mild evidence of selection on key observables such as obesity levels and socio-economic characteristics. We find evidence of selection along indicators of involvement in healthy lifestyle programmes at the school level, but the magnitude is small. Moreover, We do not find significant differences in the treatment effects of the experiment between variableswhich, albeit to a mild degree, are correlated with selection into the experiment. To our knowledge, this is the first study providing direct evidence on the magnitude of self-selection in field experiments.

Protein engineering techniques can facilitate the direct de-convolution of specific domains, regions, and particular amino acids that contribute to protein function. Many tools are available to aid this enterprise and herein we describe one such tool, a technique we term "Molecular Scanning" (MS). MS is analogous to previously described alanine scanning in that it samples potentially functional sequence space, but differs in that it uses Error-Prone polymerase chain reaction to randomly introduce all amino acids across the sequence space, as opposed to simply introducing alanine at each desired position. We commonly use MS in conjunction with ribosome-display, selecting for specific character traits (e.g., improved affinity) which allows us to sample functionally relevant diversity on a reasonably large scale. This approach is amenable to a variety of different mutational techniques and display technologies as dictated by user requirements or needs. In this chapter we present a general outline of the process as we have previously successfully applied it.

This paper investigates peer effects in the take up of a welfare programme, free school meals, using the Pupil Level Annual School Census (PLASC) which collects data on every child attending school in England. To explore the nature of the peer effect, I examine two potential channels: stigma, and information. To disentangle these channels I first exploit the fact that in a number of schools cashless catering systems have been implemented which remove the stigma associated with claiming the benefit; to investigate the impact of this innovation, telephone interviews were conducted with over 400 schools to ascertain whether and when such systems had been introduced. Second, I test whether information plays a role by comparing the peer effect for those who have claimed in previous years with those who have not. The results suggest the presence of stigma dampens the peer effect and information makes it larger. Information is found to be a more important part of the peer effect for those living in areas of greater deprivation and stigma is more important for those in the least deprived regions. The policy implication of this is that in areas of greater deprivation information campaigns will have a greater marginal impact than those that attempt to remove visible stigma.

This paper provides field evidence on the effects of diet on educational outcomes, exploiting a campaign lead in the UK in 2004, which introduced drastic changes in the meals, offered in the schools of one Borough – Greenwich - shifting from low-budget processed meals towards healthier options. We evaluate the effect of the campaign on educational outcomes in primary schools using a difference in differences approach; comparing educational outcomes in primary schools (key stage 2 outcomes more specifically) before and after the reform, using the neighbouring Local Education Authorities as a control group. We find evidence that educational outcomes did improve significantly in English and Science. We also find that the campaign lead to a 15% fall in authorised absences – which are most likely linked to illness and health.

This paper uses the Jamie Oliver Feed Me Better campaign to evaluate the impact of healthy school meals on educational outcomes. The campaign introduced drastic changes in the meals offered in the schools of one Borough, shifting from low-budget processed meals towards healthier options. We evaluate the effect of the campaign on educational outcomes using a difference in differences approach; comparing key stage 2 outcomes in primary schools before and after the reform, using the neighbouring Local Education Authorities as a control group. We find evidence that healthy school meals did improve educational outcomes, in particular in English and Science.

The entomopathogenic nematode Steinernema feltiae (Filipjev) has been shown to offer much potential for tank-mixing with chemical insecticides in a range of pest control situations. This preliminary study investigated the compatibility of S. feltiae with selected insecticides commonly used for the control of aphid pests in UK glasshouse environments. Steinernema feltiae showed a level of direct compatibility with both dimethoate and imidacloprid. Cypermethrin proved non-compatible for direct mixing with S. feltiae. The potential for tank-mixing nematodes with chemical insecticides for aphid control in UK glasshouses is discussed.

This thesis investigates the occurrence, characteristics and effects of Very Fast Transients (VFTs) associated with disconnector switching operations in Gas Insulated \ud Substations. VFTs are analysed and efforts are made to elucidate their behaviour through advanced simulation techniques. \ud The initial motivation for this work was the occurrence of a surface flashover at a spacer, leading to a prolonged outage of the circuit in question and a significant repair \ud effort. While post failure investigations were carried out by the manufacturer and yielded no significant observations, through modelling and measurements efforts while working towards this thesis, a phenomenon that could have led or contributed to the failure. \ud VFTs at a live, operational 400kV Substation (un-named for confidentiality but termed throughout as Substation ‘A’) are quantified through both modelling and measurements. \ud Significant progress in the modelling of VFTs and TEVs is demonstrated. Numerical Electromagnetic Analysis is shown to be most effective method in studying the behaviour of the GIS and earthing systems. Multiple NEA techniques are utilised, all solving a full-Maxwell’s equations through a Wave equation. The behaviour of the system (both internally and externally) is captured with great accuracy and lucidity, without the need to use analytic approximations or assumed parameters, which has traditionally been the case. Detailed models were built using equipment drawings from \ud Substation ‘A’ for the GIB, spacer-flange assembly, double-elbow assembly, disconnector, gas to air bushing. Frequency and time domain behaviour is analysed and a potential contributor to the failure at Substation ‘A’ is identified. Furthermore, elements of the earthing system were evaluated for effectiveness in mitigating TEVs.\ud The methods highlight some of flaws and inaccuracies that are present with existing ‘standard practice’ modelling efforts. The need for circuit-based modelling for VFT \ud studies is apparent, as NEA techniques at very high frequencies are limited in their interaction with the wider system. Efforts are therefore made to enhance circuit-based\ud models; utilising NEA methods and Vector Fitting to produce accurate, large bandwidth equivalent circuits, which demonstrate the computed frequency responses of the various GIS equipment types studied. Vector Fit models at lower orders of approximation are prone to unstable time domain responses, leading to numerical oscillations or even a \ud complete divergence from a solution. A method was developed to identify model orders that demonstrate stability in the time domain, allowing the lowest model order of approximation to be selected, thereby reducing the additional computational requirements of very high orders of approximation, while retaining accuracy and \ud stability in the time and frequency domains. The conversion process is augmented with a new method for identifying model orders that will be stable in the time domain.\ud Several measurement techniques and sensors were developed to capture the entire cycle of transients associated with disconnector operations. Device prototypes were designed \ud and optimised through NEA/circuit-based modelling, prior to undergoing laboratory-based measurements. Laboratory based testing was conducted using a custom built, half \ud scale GIB, with impedance matching cones at each end to allow measurement and signal generating equipment to be connected with minimal interference. While, essential, laboratory-based measurements will never replicate the transient and high EMI environmental conditions seen at a live GIS, therefore, the bulk of the measurement efforts were focused on live measurements at Substation ‘A’. Throughout the course of this project several opportunities to undertake measurements were presented and a significant amount of data was recorded. Each measurement also \ud identified areas for improvement of the measurement systems