Search

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource.

Made available in DSpace on 2022-04-28T19:29:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-07-01 Medical Research Council Canada National Institute for Health Research Objectives: To develop consensus definitions for the core outcome set for pre-eclampsia. Study design: Potential definitions for individual core outcomes were identified across four formal definition development initiatives, nine national and international guidelines, 12 Cochrane systematic reviews, and 79 randomised trials. Eighty-six definitions were entered into the consensus development meeting. Ten healthcare professionals and three researchers, including six participants who had experience of conducting research in low- and middle-income countries, participated in the consensus development process. The final core outcome set was approved by an international steering group. Results: Consensus definitions were developed for all core outcomes. When considering stroke, pulmonary oedema, acute kidney injury, raised liver enzymes, low platelets, birth weight, and neonatal seizures, consensus definitions were developed specifically for low- and middle-income countries because of the limited availability of diagnostic interventions including computerised tomography, chest x-ray, laboratory tests, equipment, and electroencephalogram monitoring. Conclusions: Consensus on measurements for the pre-eclampsia core outcome set will help to ensure consistency across future randomised trials and systematic reviews. Such standardization should make research evidence more accessible and facilitate the translation of research into clinical practice. Video abstract can be available at: www.dropbox.com/s/ftrgvrfu0u9glqd/6.%20Standardising%20definitions%20in%20teh%20pre-eclampsia%20core%20outcome%20set%3A%20a%20consensus%20development%20study.mp4?dl=0. Nuffield Department of Primary Care Health Sciences University of Oxford Institute for Women’s Health University College London Department of Women and Children’s Health School of Life Course Sciences King’s College London Department of Obstetrics and Gynecology Amsterdam UMC Academic Medical Center Academic Neonatal Medicine Imperial College London Department of Renal Medicine St George Hospital and University of New South Wales Department of Obstetrics and Gynaecology Feinberg School of Medicine Northwestern University Health Services Research Unit Nuffield Department of Population Health University of Oxford Cedars-Sinai Medical Center London North West University Healthcare NHS Trust Women’s Health Care Research Group Department of Obstetrics and Gynaecology Monash University Department of Obstetrics and Gynaecology University of Adelaide Women’s Health Research Unit Barts and The London School of Medicine and Dentistry School of Health and Related Research University of Sheffield MRC North West Hub for Trials Methodology Research Department of Biostatistics University of Liverpool Centro Rosarino de Estudios Perinatales Chelsea and Westminster Hospital NHS Foundation Trust Babcock University Ailem Academic Counselling KU Leuven Universidad Nacional de Colombia Northwell Health University of Oxford Université de Montréal University of Montreal Hospital Centre Ondokuz Mayıs University Prince Sultan Military Medical City Postgraduate Institute of Medical Education and Research King's Fertility Fetal Medicine Research Institute University Hospital Limerick Drexel University University of Aberdeen University of Groningen University of Auckland Haaglanden Medisch Centrum Nottingham University Medical School Utrecht University King Edward Memorial Hospital for Women Imperial College Healthcare NHS Trust Jean-Verdier Hospital Downland Practice University of Campinas Université Lyon University of North Carolina School of Medicine South Ural State Medical University Stellenbosch University Irish Neonatal Health Alliance University of Rzeszow Royal Brisbane and Women’s Hospital Nottingham University Hospitals NHS Trust University Hospitals of Leicester North Bristol NHS Trust University of Nottingham Soroka University Medical Center Ben Gurion University of the Negev St George’s University Hospitals NHS Foundation Trust Hospitalsenhed Midt University of Glasgow Amsterdam Universitair Medische Centra All India Institute of Medical Sciences Patna Luton and Dunstable University Hospital Khyber Medical University Institution of Medical Sciences Midwife Mid Essex Hospitals NHS Trust University of Oulu University of Michigan Bastyr University Irish Nurses and Midwives Organisation University of Toronto Barts Health NHS Trust University Hospitals Plymouth NHS Trust Burnet Institute Aga Khan University Medical University of Graz Homerton University Hospital NHS Foundation Trust Mount Royal University Université de Paris Royal Surrey County Hospital University Hospital Southampton NHS Foundation Trust University of Washington School of Nursing Evelina London Children's Hospital Neonatal Unit University of Sydney University of Leicester Academic Hospital of Udine NHS Borders Weill Cornell Medical College University of Dundee University of Edinburgh South Australian Health and Medical Research Institute University of Sheffield Monash University and Monash Health United Lincolnshire Hospitals NHS Trust University of Kwa Zulu-Natal Beatrix Hospital Keele University Government Medical College Institut Catala de la Salut. IdiapJgol University College London National Center for Child Health and Development Basavatarakam Indo-American Cancer Hospital and Research Institute Axon Anaesthesia Associates Pennine Acute Hospitals NHS Trust St George's University of London Norfolk and Norwich University Hospital Jichi Medical University School of Medicine São Paulo State University National Institute of Public Health University of Kyrenia King Edward Memorial Hospital Amsterdam University Centres University of British Columbia Chulalongkorn University University of Brescia University Of British Columbia University of Montreal Women's Clinic of Tartu University Hospital Universidade Federal de São Paulo Université de Sherbrooke University Hospital of Wales University of Iowa King's College London Westmead Hospital Princess Royal Maternity Leipzig University Centre Hospitalier Public du Cotentin Lewisham and Greenwich NHS Trust Juntendo University Faculty of Medicine Western Sydney University National Institute of Health Research University of Washington Baylor College of Medicine Capelle aan den Ijssel Sanatorio Anchorena Oxford University Hospitals NHS Foundation Trust University of Leeds Institute of Medical Sciences UPMC Magee Womens Hospital Penn Medicine Princeton Health University of North Carolina at Chapel Hill São Paulo State University

Background\ud \ud No phase 3 trial has yet shown improved survival for patients with pleural or peritoneal malignant mesothelioma who have progressed following platinum-based chemotherapy. The aim of this study was to assess the efficacy and safety of nivolumab, an anti-PD-1 antibody, in these patients.\ud \ud \ud Methods\ud \ud This was a multicentre, placebo-controlled, double-blind, parallel group, randomised, phase 3 trial done in 24 hospitals in the UK. Adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1, with histologically confirmed pleural or peritoneal mesothelioma, who had received previous first-line platinum-based chemotherapy and had radiological evidence of disease progression, were randomly assigned (2:1) to receive nivolumab at a flat dose of 240 mg every 2 weeks over 30 min intravenously or placebo until disease progression or a maximum of 12 months. The randomisation sequence was generated within an interactive web response system (Alea); patients were stratified according to epithelioid versus non-epithelioid histology and were assigned in random block sizes of 3 and 6. Participants and treating clinicians were masked to group allocation. The co-primary endpoints were investigator-assessed progression-free survival and overall survival, analysed according to the treatment policy estimand (an equivalent of the intention-to-treat principle). All patients who were randomly assigned were included in the safety population, reported according to group allocation. This trial is registered with Clinicaltrials.gov, NCT03063450.\ud \ud \ud Findings\ud \ud Between May 10, 2017, and March 30, 2020, 332 patients were recruited, of whom 221 (67%) were randomly assigned to the nivolumab group and 111 (33%) were assigned to the placebo group). Median follow-up was 11·6 months (IQR 7·2–16·8). Median progression-free survival was 3·0 months (95% CI 2·8–4·1) in the nivolumab group versus 1·8 months (1·4–2·6) in the placebo group (adjusted hazard ratio [HR] 0·67 [95% CI 0·53–0·85; p=0·0012). Median overall survival was 10·2 months (95% CI 8·5–12·1) in the nivolumab group versus 6·9 months (5·0–8·0) in the placebo group (adjusted HR 0·69 [95% CI 0·52–0·91]; p=0·0090). The most frequently reported grade 3 or worse treatment-related adverse events were diarrhoea (six [3%] of 221 in the nivolumab group vs two [2%] of 111 in the placebo group) and infusion-related reaction (six [3%] vs none). Serious adverse events occurred in 90 (41%) patients in the nivolumab group and 49 (44%) patients in the placebo group. There were no treatment-related deaths in either group.\ud \ud \ud Interpretation\ud \ud Nivolumab represents a treatment that might be beneficial to patients with malignant mesothelioma who have progressed on first-line therapy.\ud \ud \ud Funding\ud \ud Stand up to Cancer–Cancer Research UK and Bristol Myers Squibb.

Made available in DSpace on 2022-04-28T19:28:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-01 National Institute for Health Research Barts Charity Objective: To develop a core outcome set for pre-eclampsia. Design: Consensus development study. Setting: International. Population: Two hundred and eight-one healthcare professionals, 41 researchers and 110 patients, representing 56 countries, participated. Methods: Modified Delphi method and Modified Nominal Group Technique. Results: A long-list of 116 potential core outcomes was developed by combining the outcomes reported in 79 pre-eclampsia trials with those derived from thematic analysis of 30 in-depth interviews of women with lived experience of pre-eclampsia. Forty-seven consensus outcomes were identified from the Delphi process following which 14 maternal and eight offspring core outcomes were agreed at the consensus development meeting. Maternal core outcomes: death, eclampsia, stroke, cortical blindness, retinal detachment, pulmonary oedema, acute kidney injury, liver haematoma or rupture, abruption, postpartum haemorrhage, raised liver enzymes, low platelets, admission to intensive care required, and intubation and ventilation. Offspring core outcomes: stillbirth, gestational age at delivery, birthweight, small-for-gestational-age, neonatal mortality, seizures, admission to neonatal unit required and respiratory support. Conclusions: The core outcome set for pre-eclampsia should underpin future randomised trials and systematic reviews. Such implementation should ensure that future research holds the necessary reach and relevance to inform clinical practice, enhance women's care and improve the outcomes of pregnant women and their babies. Tweetable abstract: 281 healthcare professionals, 41 researchers and 110 women have developed #preeclampsia core outcomes @HOPEoutcomes @jamesmnduffy. [Correction added on 29 June 2020, after first online publication: the order has been corrected.]. Nuffield Department of Primary Care Health Sciences University of Oxford Institute for Women's Health University College London Department of Obstetrics and Gynaecology Amsterdam UMC Academic Medical Centre Academic Neonatal Medicine Imperial College London Department of Renal Medicine St George Hospital and University of New South Wales Department of Women and Children's Health School of Life Course Sciences King's College London Department of Obstetrics and Gynecology Feinberg School of Medicine Northwestern University Health Services Research Unit Nuffield Department of Population Health University of Oxford Cedars-Sinai Medical Center Vascular Biology Research Centre Molecular and Clinical Sciences Research Institute St George's University of London London North West University Healthcare NHS Trust Department of Obstetrics and Gynaecology Monash University Department of Obstetrics and Gynaecology University of Adelaide Women's Health Research Unit Barts and the London School of Medicine and Dentistry School of Health and Related Research University of Sheffield MRC North West Hub for Trials Methodology Research Department of Biostatistics University of Liverpool Centro Rosarino de Estudios Perinatales Chelsea and Westminster Hospital NHS Foundation Trust Babcock University Ailem Academic Counselling KU Leuven Universidad Nacional de Colombia Northwell Health University of Oxford Université de Montréal University of Montreal Hospital Centre Ondokuz Mayis University Prince Sultan Military Medical City Postgraduate Institute of Medical Education and Research Chandigarh University Hospital Limerick Drexel University University of Aberdeen University of Groningen University of Auckland Haaglanden Medisch Centrum Nottingham University Medical School Utrecht University King Edward Memorial Hospital for Women Imperial College Healthcare NHS Trust Jean-Verdier Hospital Downland Practice University of Campinas Université Lyon University of North Carolina School of Medicine South Ural State Medical University Stellenbosch University Irish Neonatal Health Alliance University of Rzeszow Royal Brisbane and Women's Hospital Nottingham University Hospitals NHS Trust University Hospitals of Leicester North Bristol NHS Trust University of Nottingham Soroka University Medical Centre Ben Gurion University of the Negev St George's University Hospitals NHS Foundation Trust Hospitalsenhed Midt University of Glasgow Postgraduate Institute of Medical Education and Research Amsterdam Universitair Medische Centra All India Institute of Medical Sciences Patna Luton and Dunstable University Hospital Khyber Medical University Institution of Medical Sciences Midwife Mid Essex Hospitals NHS Trust University of Oulu University of Michigan Bastyr University Irish Nurses and Midwives Organisation University of Toronto Barts Health NHS Trust University Hospitals Plymouth NHS Trust Burnet Institute Aga Khan University Medical University of Graz Homerton University Hospital NHS Foundation Trust Mount Royal University Université de Paris Royal Surrey County Hospital University Hospital Southampton NHS Foundation Trust University of Washington School of Nursing Evelina London Children's Hospital Neonatal Unit University of Sydney University of Leicester Academic Hospital of Udine NHS Borders Weill Cornell Medical College University of Dundee University of Edinburgh South Australian Health and Medical Research Institute University of Sheffield Monash University and Monash Health United Lincolnshire Hospitals NHS Trust University of Kwa Zulu-Natal Beatrix Hospital Keele University Government Medical College Nagpur Institut Catala de la Salut. IdiapJgol University College London National Centre for Child Health and Development Basavatarakam Indo-American Cancer Hospital and Research Institute Axon Anaesthesia Associates Pennine Acute Hospitals NHS Trust St George's University of London Norfolk and Norwich University Hospital Jichi Medical University School of Medicine São Paulo State University National Institute of Public Health University of Kyrenia King Edward Memorial Hospital Amsterdam University Centres University of British Columbia Chulalongkorn University University of Brescia University of Montreal Women's Clinic of Tartu University Hospital Universidade Federal de São Paulo Université de Sherbrooke University Hospital of Wales University of Iowa King's College London Westmead Hospital Princess Royal Maternity Leipzig University Centre Hospitalier Public du Cotentin Lewisham and Greenwich NHS Trust Juntendo University Faculty of Medicine Western Sydney University National Institute of Health Research University of Washington Baylor College of Medicine Capelle aan den Ijssel Sanatorio Anchorena Oxford University Hospitals NHS Foundation Trust University of Leeds Institute of Medical Sciences Lahore UPMC Magee Womens Hospital Penn Medicine Princeton Health University of North Carolina at Chapel Hill USA and Dr Arnold G. Zermansky University of Leeds São Paulo State University

We investigate the relationship between deposit growth and branch deposit competitiveness. We introduce a new measure of competitiveness focused at the branch level that utilizes granular product data. We find more competitive branches have higher rates of deposit growth that vary across product types and local market structures. The new measure of competitiveness at the branch level is intended to complement existing bank and market-level measures of competition and opens up a number of new opportunities for banking research and policy investigation.

Background: Young people (aged 16-24 years) with long-term health conditions can disengage from health services, resulting in poor health outcomes, but clinicians in the UK National Health Service (NHS) are using digital communication to try to improve engagement. Evidence of effectiveness of this digital communication is equivocal. There are gaps in evidence as to how it might work, its cost, and ethical and safety issues.Objective: Our objective was to understand how the use of digital communication between young people with long-term conditions and their NHS specialist clinicians changes engagement of the young people with their health care; and to identify costs and necessary safeguards.Methods: We conducted mixed-methods case studies of 20 NHS specialist clinical teams from across England and Wales and their practice providing care for 13 different long-term physical or mental health conditions. We observed 79 clinical team members and interviewed 165 young people aged 16-24 years with a long-term health condition recruited via case study clinical teams, 173 clinical team members, and 16 information governance specialists from study NHS Trusts. We conducted a thematic analysis of how digital communication works, and analyzed ethics, safety and governance, and annual direct costs.Results: Young people and their clinical teams variously used mobile phone calls, text messages, email, and voice over Internet protocol. Length of clinician use of digital communication varied from 1 to 13 years in 17 case studies, and was being considered in 3. Digital communication enables timely access for young people to the right clinician at the time when it can make a difference to how they manage their health condition. This is valued as an addition to traditional clinic appointments and can engage those otherwise disengaged, particularly at times of change for young people. It can enhance patient autonomy, empowerment and activation. It challenges the nature and boundaries of therapeutic relationships but can improve trust. The clinical teams studied had not themselves formally evaluated the impact of their intervention. Staff time is the main cost driver, but offsetting savings are likely elsewhere in the health service. Risks include increased dependence on clinicians, inadvertent disclosure of confidential information, and communication failures, which are mostly mitigated by young people and clinicians using common-sense approaches.Conclusions: As NHS policy prompts more widespread use of digital communication to improve the health care experience, our findings suggest that benefit is most likely, and harms are mitigated, when digital communication is used with patients who already have a relationship of trust with the clinical team, and where there is identifiable need for patients to have flexible access, such as when transitioning between services, treatments, or lived context. Clinical teams need a proactive approach to ethics, governance, and patient safety.

BACKGROUND: To evaluate safety and efficacy of ipilimumab combined with standard first-line chemotherapy for patients with extensive stage SCLC.METHODS: Chemotherapy-naïve extensive stage SCLC patients were treated with carboplatin and etoposide up to six cycles. Ipilimumab 10 mg/kg was given on day 1 of cycles 3-6 and every 12 weeks. Response was assessed by RECIST v1.0 and immune related response criteria (irRC). The primary endpoint was 1-year progression-free survival (PFS) according to RECIST. Secondary endpoints included PFS by irRC (irPFS) and overall survival (OS). Autoantibody serum levels were evaluated and correlated with clinical outcomes.RESULTS: 42 patients were enrolled between September 2011-April 2014, 39 evaluable for safety and 38 for efficacy. 6/38 patients (15.8% [95% CI: 7.4%-30.4%]) were alive and progression-free at 1-year by RECIST. Median PFS was 6.9 months (95%CI: 5.5-7.9). Median irPFS was 7.3 months (95% CI: 5.5-8.8). Median OS was 17.0 months (95% CI: 7.9-24.3). In patients evaluable for response, 21/29 patients (72.4%) achieved an objective response by RECIST and 28/33 (84.8%) by irRC. All patients experienced at least one adverse event; 35/39 (89.7%) patients developed at least one toxicity ? Grade 3; in 27 (69.2%) this was related to ipilimumab. Five deaths were reported to be related to ipilimumab. The positivity of an autoimmune profile at baseline was associated with improved outcomes and severe neurological toxicity.CONCLUSION: Ipilimumab in combination with carboplatin and etoposide might benefit a subgroup of patients with advanced SCLC. Autoantibody analysis correlates with treatment benefit and toxicity and warrants further investigation.

Effective systemic therapies for patients with advanced, progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce. We aimed to assess the efficacy and safety of everolimus compared with placebo in this patient population.In the randomised, double-blind, placebo-controlled, phase 3 RADIANT-4 trial, adult patients (aged ≥18 years) with advanced, progressive, well-differentiated, non-functional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide. Eligible patients were randomly assigned in a 2:1 ratio by an interactive voice response system to receive everolimus 10 mg per day orally or identical placebo, both with supportive care. Patients were stratified by tumour origin, performance status, and previous somatostatin analogue treatment. Patients, investigators, and the study sponsor were masked to treatment assignment. The primary endpoint was progression-free survival assessed by central radiology review, analysed by intention to treat. Overall survival was a key secondary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01524783.Between April 3, 2012, and Aug 23, 2013, a total of 302 patients were enrolled, of whom 205 were allocated to everolimus 10 mg per day and 97 to placebo. Median progression-free survival was 11·0 months (95% CI 9·2-13·3) in the everolimus group and 3·9 months (3·6-7·4) in the placebo group. Everolimus was associated with a 52% reduction in the estimated risk of progression or death (hazard ratio [HR] 0·48 [95% CI 0·35-0·67], p0·00001). Although not statistically significant, the results of the first pre-planned interim overall survival analysis indicated that everolimus might be associated with a reduction in the risk of death (HR 0·64 [95% CI 0·40-1·05], one-sided p=0·037, whereas the boundary for statistical significance was 0·0002). Grade 3 or 4 drug-related adverse events were infrequent and included stomatitis (in 18 [9%] of 202 patients in the everolimus group vs 0 of 98 in the placebo group), diarrhoea (15 [7%] vs 2 [2%]), infections (14 [7%] vs 0), anaemia (8 [4%] vs 1 [1%]), fatigue (7 [3%] vs 1 [1%]), and hyperglycaemia (7 [3%] vs 0).Treatment with everolimus was associated with significant improvement in progression-free survival in patients with progressive lung or gastrointestinal neuroendocrine tumours. The safety findings were consistent with the known side-effect profile of everolimus. Everolimus is the first targeted agent to show robust anti-tumour activity with acceptable tolerability across a broad range of neuroendocrine tumours, including those arising from the pancreas, lung, and gastrointestinal tract.Novartis Pharmaceuticals Corporation.

This document presents the conclusions of the Optimising ICT study into the effects of ICT on the policy process. The remit of the study has evolved to examine the disjunction between physical markets and their online counterparts caused by the presence of ICT factors that either elude policymakers altogether or cannot be avoided. The report traces the study from its inception and intellectual origins in the Eco Search initiative to optimise online energy labelling through to conclusions and recommendations in the form of a tool box. The starting point is the recognition that ICTs profoundly influence policy formulation and effectiveness across a range of domains. This linkage is (potentially) two-way: ICTs may contribute to or help address problems in ‘non-ICT’ areas; conversely, ‘non-ICT’ considerations may need to be taken into specific account when formulating ostensibly ICT-centric policy. One source of this linkage is the emergence of on-line substitutes or complements for off-line activities; another is the potential of data generated and mediated by this on-line migration to expose incorrect or obsolete assumptions and to indicate where interventions could be improved, reduced, cross-linked or reoriented. The potential of these links is limited by the fact that institutions with specific policy responsibilities tend to collect information of most relevance to their own obligations and perspectives and are sometimes reluctant to share information, collect data on behalf of others or collaborate in developing solutions. We use the term ‘Internet-ready’ to denote areas with the potential for more effective and appropriate interventions based on the on-line migration of off-line activities – and especially where existing instruments and legal frameworks allow as-yet-unrealised adaptation in interventions and policy processes. This report considers their identification, prioritisation and management. The document should and must be read as a first foray into the domain; therefore we have used three indicative examples (Deep Dives) in order to develop a general approach and a series of conclusions. The first part of the document discusses the intellectual and operational context of the study.

This report was commissioned to provide background information and advice on Smart Cities in the European Union (EU) and to explain how existing mechanisms perform. In exploring this, a working definition of a Smart City is established and the cities fitting this definition across the Member States are mapped. An analysis of the objectives and Europe 2020 targets of Smart City initiatives finds that despite their early stage of development, Smart City objectives should be more explicit, well defined and clearly aligned to city development, innovation plans and Europe 2020 in order to be successful.

Ubiquitous solutions providing access from anywhere at any time are a next step for government and commercial services, and are expected to result in lower costs, increased flexibility, and an enhanced user experience. These solutions, based on modern cloud technologies, may facilitate re-use across borders, avoid duplication and achieve scale economics as well as cross-border interoperability for e-government services.

The Committee on Industry, Research and Energy (ITRE) has requested an ad hoc briefing paper to provide its Members with information and advice regarding the proposed General Data Protection Regulation (2012/0011(COD)). This document presents a rapid assessment of the innovation and competitiveness impacts of the measures affecting: automated processing; control of data processing; and data transfers. It considers a variety of perspectives: profiling; big data; cloud computing; and privacy-friendly technologies and identifies a variety of impacts, and areas for improvement. LIST OF ABBREVIATIONS 5 LIST OF TABLES 7 LIST OF FIGURES 7 EXECUTIVE SUMMARY 8 1. INTRODUCTION 15 1.1. Why this study is relevant 15 1.2. Problem statement 16 1.2.1. Automated data processing and profiling 17 1.2.2. Data controllers’ obligation to control data processing 17 1.2.3. Data migration 17 1.3. Objectives 18 1.3.1. General objectives 18 1.3.2. Specific objectives 18 1.4. Options 19 1.5. Structure of this report 19 2. BACKGROUND AND CONTEXT 21 2.1. Introduction 21 2.2. Economic and market framing 23 2.2.1. The relation between privacy, competitiveness and innovation 23 2.2.2. The data processing value network 25 2.2.3. How data protection provisions affect market outcomes 26 2.2.4. Measuring these effects 28 2.3. Legal and Regulatory context 34 2.3.1. The current Directive and its implementation across Member States 34 2.3.2. The proposed new Regulation 37 2.3.3. Comparison to the US 42 3. CASE STUDIES 46 3.1. Introduction 46 3.2. Case Study Selection 47 3.3. Profiling, Behavioural Advertising, Cookies and Social Media 47 3.3.1. Introduction 47 3.3.2. Impact by provision 48 3.3.3. Impacts on competitiveness and innovation 50 3.3.4. Tensions and concluding remarks 51 PE 492.463 3 Policy Department A: Economic and Scientific Policy 3.4. Big Data (BD) 51 3.4.1. Introduction 51 3.4.2. Impact by provision 52 3.4.3. Impacts on competitiveness and innovation 53 3.4.4. Tensions and concluding remarks 55 3.5. Cloud Computing 56 3.5.1. Introduction 56 3.5.2. Impact by provision 57 3.5.3. Impacts on competitiveness and innovation 59 3.5.4. Tensions and concluding remarks 60 3.6. Privacy Friendly Technologies (PETs) 60 3.6.1. Introduction 60 3.6.2. Impact by provision 60 3.6.3. Impacts on competitiveness and innovation 61 3.6.4. Tensions and concluding remarks 62 4. EMERGING FINDINGS AND PRELIMINARY RECOMMENDATIONS 63 4.1. Introduction 63 4.2. Conclusions from the cases 64 4.2.1. Impacts related to the specific provisions of the options 65 4.2.2. More general impacts arising in the value network 66 4.3. Lessons regarding competitiveness 70 4.3.1. Implications arising from compliance costs 71 4.3.2. Implications arising from innovation 72 4.3.3. Implications arising from regulatory and market uncertainty 72 4.4. Lessons regarding innovation 74 4.5. Comparing the options 74 4.5.1. Option 0 74 4.5.2. Option 1 76 4.5.3. Option 2 76 4.5.4. Summary Table 77 4.5.5. Preferred option 79 REFERENCES 81 Annex A. Interview Protocol 86 Annex B. Anonymised List of Interviewees 91 Annex C. Comparison of relevant terms of Directive 95/46/EC and proposed Regulation 92

This study investigates the interplay between Internet innovation and privacy. We propose working definitions of innovation and privacy and review the literature about their interaction. We interpret the possible tensions and problems in terms of market and system failures and analyse the relevant legal and policy aspects in relation to examples of privacy invasion and/or protection by innovating companies. Using a four issue framework we analyse relevant case studies such as cloud computing and online behavioural advertising. Following a gap analysis according to our model of failure, we present a series of recommendations aimed at different stakeholders. The study was based on desk research, key informant interviews, case studies and an interactive expert consultation held in Brussels in June 2011. CONTENTS Contents 3 LIST OF ABBREVIATIONS 6 LIST OF TABLES 8 LIST OF FIGURES 8 Executive SUMMARY 9 1. Introduction 18 1.1. The research behind this study 19 1.2. Structure of this report 19 2. Background 20 2.1. Working definitions of Internet innovation and privacy 20 2.1.1. Internet innovation 20 2.1.2. Privacy 22 2.2. Main elements of current regulations applying directly to those in the Internet economy 26 2.2.1. Directive 95/46/EC - the General Data Protection Directive 27 2.2.2. Revised EU telecom regulatory framework 2009 30 2.2.3. Directive 2006/24/EC (Data Retention Directive) 32 2.2.4. A comprehensive approach on personal data protection in the European Union: Communication of the European Commission (2010)609 33 2.2.5. Privacy regulations and innovation 34 2.3. The supranational European context 36 2.3.1. The EU Charter on Fundamental Rights 37 2.3.2. Treaty on the Functioning of the European Union (TFEU) 38 2.3.3. European Convention on Human Rights 39 2.4. Examples of EU Member State policy initiatives 39 2.4.1. Consent 40 2.4.2. The right to be forgotten 40 2.4.3. Public & private spaces 42 3 PE 464.462 Policy Department A: Economic and Scientific Policy 2.4.4. Responsibility for Privacy and security 43 2.4.5. Towards a more stringent consent test for cookies 43 3. Current and future tensions 46 3.1. Who cares about privacy? 46 3.2. What do Internet innovators do to protect and/or abuse privacy? 51 3.2.1. Classification of activities 51 3.2.2. Why use personal data? 52 3.2.3. A framework for economically valuing privacy 54 3.2.4. Information Protection 55 3.2.5. Information disclosure 56 3.2.6. Privacy enhancing technologies (PETs) 58 4. Empirical findings 62 4.1. Radio Frequency Identification (RFID) 63 4.2. Biometrics 69 4.3. Online behavioural advertising 73 4.4. Location based services (LBS) 77 4.5. Cloud computing 81 5. Key findings and Recommendations 87 5.1. Introduction 88 5.2. Conclusions on privacy and Internet innovation 88 5.2.1. Generic conclusions 88 5.2.2. Conclusions on emerging technologies 89 5.2.3. Conclusions on business practices 90 5.2.4. Conclusions on user behaviour and attitudes 91 5.2.5. Conclusions on legal and regulatory issues 92 5.3. Recommendations 94 5.3.1. Privacy rights and responsibilities 94 5.3.2. Rules and regulations 94 5.3.3. Coping with change 95 4 PE 464.462 Does it help or hinder? Promotion of Innovation on the Internet and Citizens' Right to Privacy 5.4. Recommendations in detail 97 5.4.1. Privacy rights and responsibilities 97 5.4.2. Rules and regulations 100 5.4.3. Coping with change 101 References 104 Annex - Interviewees 111 Consultation Meeting 113

BACKGROUND There are concerns regarding whether antibiotic therapy confers significant benefit in the treatment of acute bacterial conjunctivitis. OBJECTIVES The aim of this review is to assess the benefit and harm of antibiotic therapy in the management of acute bacterial conjunctivitis. SEARCH STRATEGY We searched the Cochrane Eyes and Vision Group specialised register, the Cochrane Controlled Trials Register - Central, MEDLINE and the reference lists of identified trial reports. We used the Science Citation Index to look for articles that cited the relevant studies, and we contacted investigators and pharmaceutical companies for information about additional trials. The most recent searches were carried out in September 1998. SELECTION CRITERIA We included double masked randomised controlled trials in which any form of antibiotic treatment had been compared with placebo in the management of acute bacterial conjunctivitis. This included topical, systemic and combination (for example, antibiotics and steroids) antibiotic usage. DATA COLLECTION AND ANALYSIS One reviewer extracted data and the accuracy was checked by a second reviewer. Relative risks were summarised. We tested for heterogeneity between studies. MAIN RESULTS Six published trials were identified of which three fulfilled the eligibility criteria for inclusion in this review. One trial was single masked and therefore excluded. A second report, when translated, was found to have no placebo group and was therefore excluded. One trial is currently 'awaiting assessment'. This has been published in abstract form and has yet to be fully reported. All the trials thus far identified appear to have been conducted on a selected specialist care patient population. The trials were heterogeneous in terms of their inclusion and exclusion criteria, the nature of the intervention, and the outcome measures assessed. Meta-analysis indicates that acute bacterial conjunctivitis is frequently a self-limiting condition, as clinical remission (cure or significant improvement) occurred by days two to five in 64% (95% confidence interval (CI) 57% to 71%) of those treated with placebo. Treatment with antibiotics was, however, associated with significantly better rates of clinical remission (days two to five: relative risk (RR) 1.31 95% CI 1.11 to 1.55, NNT=5) with a suggestion that this benefit was maintained for late clinical remission (days six to 10: RR 1.27 95% CI 1.00 to 1.61, NNT=5). Antibiotic treatment was associated with rates of microbiological remission (pathogen eradication or reduction). No serious outcomes were reported in either the active or placebo arms of these trials, indicating that important sight-threatening complications are an infrequent occurrence. REVIEWER'S CONCLUSIONS Acute bacterial conjunctivitis is frequently a self-limiting condition but the use of antibiotics is associated with significantly improved rates of early clinical remission and early and late microbiological remission. Since trials to-date have been conducted in selected specialist care patient populations these results may not necessarily be generalisable to a primary care based population. A trial based in primary care designed to assess the cost-effectiveness of commonly prescribed antibiotic(s) versus placebo in acute bacterial conjunctivitis is warranted.

The interactions of partially melted Er-Ba-Cu-O superconductors with various substrates including MgO, TiO₂, SiC and PSZ were studied with the objective of finding an adequate buffer layer for a nickel-HTSC composite. Bulk ErBa₂Cu₃Oₓ pellets were melt-textured on the substrates and the superconductive properties of the composites were assessed by AC susceptibility. In the present paper, microstructure of the textured superconductors and the interfaces are described. Contamination of 123 grains by the various materials and the composition of the reaction products are presented.

n/a

Introduction: Neuroendocrine tumors of the lung (Lung-NETs) make up a heterogenous family of neoplasms showing neuroendocrine differentiation and encompass carcinoids and neuroendocrine carcinomas. On molecular grounds, they considered two completely distinct and separate tumor groups with no overlap of molecular alterations nor common developmental mechanisms. Areas covered: Two perspectives were evaluated based on an extensive review and rethinking of literature: (1) the current classification as an instrument to obtaining clinical and molecular insights into the context of Lung-NETs; and (2) an alternative and innovative interpretation of these tumors, proposing a tripartite separation into early aggressive primary high-grade neuroendocrine tumors (HGNET), differentiating or secondary HGNET, and indolent NET. Expert opinion: We herein provide an alternative outlook on Lung-NETs, which is a paradigm shift to current pathogenesis models and expands the understanding of these tumors.

Item does not contain fulltext