Correspondence between Lionel Wharrard and David de Verteuil: Part 2

Correspondence about acquiring promotional copies of the winning nove

Letter from D.J. de Verteuil to John Murphy

Papers relating to Booker Prize publicity, including promotional materials: 2 Feb -11 May 197

Mission Today

Send us brothers and sisters, Michel de VerteuilRemembering Michel, Lucy Klein-Gebbinc

Economic evaluation of laparoscopic surgery for colorectal cancer

Objectives: To assess the cost-effectiveness of laparoscopic surgery compared with open surgery for the treatment of colorectal cancer. Methods: A Markov model was developed to model cost-effectiveness over 25 years. Data on the clinical effectiveness of laparoscopic and open surgery for colorectal cancer were obtained from a systematic review of the literature. Data on costs came from a systematic review of economic evaluations and from published sources. The outcomes of the model were presented as the incremental cost per life year gained and using cost-effectiveness acceptability curves (CEACs) to illustrate the likelihood that a treatment was cost-effective at various threshold values for society’s willingness to pay for an additional life year. Results: Laparoscopic surgery was on average £300 more costly and slightly less effective than open surgery and had a 30% chance of being cost-effective if society is willing to pay £30,000 for a life year. One interpretation of the available data suggests equal survival and disease-free survival. Making this assumption, laparoscopic surgery had a greater chance of being considered cost-effective. Presenting the results as incremental cost per quality adjusted life year (QALY) made no difference to the results, as utility data were poor. Evidence suggests short-term benefits following laparoscopic repair. This benefit would have to be at least 0.01 of a QALY for laparoscopic surgery to be considered cost-effective. Conclusions: Laparoscopic surgery is likely to be associated with short-term quality of life benefits, similar long-term outcomes and an additional £300 per patient. A judgement is required as to whether the short-term benefits are worth this extra cost.Peer reviewedAuthor versio

Co-operatives, Work, and the Digital Economy: A Knowledge Synthesis Report

This report surveys recent literature on co-operative approaches to improving work and livelihoods in the digital economy, specifically in the gig economy, the tech sector, and digital creative industries. It introduces concepts that update co-operative theory and practice for the digital age, including platform cooperativism, open cooperativism, distributed co-operative organizations, and Exit to Community. It outlines how the co-operative model has been adopted by and for self-employed workers, platform workers, technologists and communication professionals, and data subjects. While the report presents evidence of co-ops’ potential to improve working conditions and mitigate power asymmetries in the digital economy, it also addresses challenges co-ops face. It explores perspectives on the infrastructure necessary to overcome these challenges and expand worker co-ops’ presence in the digital economy, including the formation of co-operative federations for sharing technology across co-ops. Despite the promise of co-ops in the digital economy, the literature cautions against viewing them as a panacea. Stressing that individual co-ops are not, on their own, a sufficient response to problems of work and inequality, several authors position co-ops as one among a diversity of worker-centered organizations and strategies necessary to improve work and livelihoods in the digital economy. The report concludes with suggestions for future research and policy recommendations

Systematic review of economic evaluations of laparoscopic surgery for colorectal cancer

Objective Colorectal cancer is one of the most common cancers and the standard surgical treatment for this cancer is open resection (OS), but laparoscopic surgery (LS) may be an alternative treatment. In 2000, a Health Technology Assessment (HTA) review found little evidence on costs and cost-effectiveness in comparing the two methods. The evidence base has since expanded and this study systematically reviews the economic evaluations on the subject published since 2000. Method Systematic review of studies reporting costs and outcomes of LS vs OS for colorectal cancer. National Health Service Economic Evaluation Database (NHS EED) methods for abstract writing were followed. Studies were summarized and incremental cost-effectiveness ratios (ICER) for common outcomes were calculated. Results Five studies met the inclusion criteria. LS generally had higher healthcare costs. Most studies reported longer operational time and shorter length of stay and similar long-term outcomes with LS vs OS. Only one outcome, complications, was common across all studies but results lacked consistency (e.g. in two studies, OS was less costly but more effective; in another study, LS was less costly but more effective; and in the further two studies, LS could potentially be cost effective depending on the decision-makers' willingness to pay for the health gain). Conclusion The evidence on cost-effectiveness is not consistent. LS was generally more costly than OS. However, the effectiveness data used in individual economic evaluation were imprecise and unreliable when compared with data from systematic reviews of effectiveness. Nevertheless, short-term benefits of LS (e.g. shorter recovery) may make LS appear less costly when productivity gains are considered.Department of Health, National Coordinating Centre for Health Technology Assessment, Chief Scientist Office of the Scottish Government Health DirectoratesPeer reviewedAuthor versio

L’immunoprotéasome : producteur de peptides-CMH I et régulateur de l’expression génique

Le système ubiquitine-protéasome est le principal mécanisme par lequel les protéines intracellulaires sont dégradées. Le protéasome dit constitutif (PC) est donc essentiel à l’homéostasie mais aussi à la régulation de la majorité des processus cellulaires importants. La découverte d’un deuxième type de protéasome, appelé immunoprotéasome (IP), soulève toutefois de nouvelles questions. Pourquoi existe-t-il plus d’un type de protéasome ? L’IP a-t-il des rôles redondants ou complémentaires avec le PC ? L’IP étant présent principalement dans les cellules immunitaires ou stimulées par des cytokines, plusieurs groupes ont tenté de définir son rôle dans la réponse immunitaire. Or, l’implication de son homologue constitutif dans un éventail de processus non spécifiquement immunitaires nous laisse croire que l’IP pourrait lui aussi avoir un impact beaucoup plus large. L’objectif de cette thèse était donc de caractériser certains rôles cellulaires de l’IP dans les cellules dendritiques. Nous avons d’abord étudié l’impact global de l’IP sur la présentation antigénique de classe I. Ce faisant, nous avons pu déterminer ses deux contributions principales, soit l’augmentation drastique du nombre et de la diversité des peptides présentés sur les complexes majeurs d’histocompatibilité de classe I. Les différences de clivage entre le PC et l’IP pourraient expliquer en partie cette diversité du répertoire peptidique, notamment par l’affinité apparente de l’IP pour les régions protéiques non structurées. Dans un deuxième temps, nous avons dévoilé un nouveau rôle de l’IP sur un processus dépassant le cadre immunitaire : la transcription. Nous avons découvert que l’IP modifie l’abondance des ARNm en agissant principalement au niveau de leur synthèse. L’impact de l’IP sur le transcriptome est majeur et serait dû en partie à une dégradation différente de facteurs de transcription des familles IRF, STAT et NF-kB. Les cellules dendritiques IP-déficientes activent moins efficacement les lymphocytes T CD8+ et nous croyons que cette défaillance est causée (du moins en partie) par la perturbation transcriptomique provoquée par l’absence d’IP. Il importe donc de comprendre les différents rôles moléculaires de l’IP afin de mieux définir sa contribution globale au fonctionnement de la cellule et comprendre l’avantage évolutif, au niveau de l’organisme, procuré par une telle plasticité du système ubiquitine-protéasome.The ubiquitin-proteasome system is the major mechanism by which intracellular proteins get degraded. Constitutive proteasomes (CPs) are thus essential for cellular homeostasis but also to regulate the majority of important cellular processes. However, the discovery of a second type of proteasome, named immunoproteasome (IP), raises new questions. Why are there more than one type of proteasome? Does the IP perform redundant or complementary roles with the CP? The IP is predominantly expressed in immune or cytokine-stimulated cells and several groups worked at defining its role during the immune response. Yet, the implication of its constitutive homolog in a variety of processes suggests that the IP may also have a much broader impact. The objective was to characterize cellular roles of the IP in dendritic cells. We first studied the global impact of the IP on class I antigen presentation. We discovered that the IP drastically increases the number and the diversity of peptide presented by class I major histocompatibility complexes. Cleavage differences between the CP and the IP are likely part of the explanation for this peptide repertoire diversity, notably due to IP’s apparent affinity for unstructured protein regions. Second, we discovered a new role for the IP in a process unrestricted to the immune system: transcription. We found that the IP affects transcript abundance mostly at the level of mRNA synthesis. The impact of IPs on the transcriptome is major and would be partly based on a different degradation of IRF, STAT and NF-kB transcription factor family members by the two types of proteasomes. IP-deficient dendritic cells are less potent activators of CD8+ T cells and we believe that this defect is at least partly caused by the transcriptome alterations induced by the absence of IPs. It is therefore important to understand the different molecular roles of the IP in order to better define its global contribution to cellular functions and to understand the evolutionary advantage, at the level of the organism, brought by such plasticity of the ubiquitin- proteasome system

Economic evaluation of the treatment of grade II haemorrhoids : a comparison of stapled haemorrhoidopexy and rubber band ligation.

The definitive version is available at www3.interscience.wiley.comPeer reviewedPostprin