The self-extinguishing despot: Millian Democratization

Although there is no more iconic, stalwart, and eloquent defender of liberty and representative democracy than J. S. Mill, he sometimes endorses nondemocratic forms of governance. This article explains the reasons behind this seeming aberration and shows that Mill actually has complex and nuanced views of the transition from nondemocratic to democratic government, including the comprehensive and parallel material, cultural, institutional, and character reforms that must occur, and the mechanism by which they will be enacted. Namely, an enlightened despot must cultivate democratic virtues such as obedience, industriousness, spirit of nationality, and resistance to tyranny in the population and simultaneously prepare the way for his own demise and secure his own legitimacy by transitioning to the rule of law. This challenges recent scholarship that paints Mill's nondemocratic views as crudely and uncritically imperialist, because it fails to recognize and engage seriously with his sophisticated (if ultimately problematic) theory of individual and institutional development under enlightened colonialism. © Copyright Southern Political Science Association 2011.published_or_final_versio

Predictors of pain relief following spinal cord stimulation in chronic back and leg pain and failed back surgery syndrome: a systematic review and meta-regression analysis

This is the final version of the article. Available from the publisher via the DOI in this record.We sought to assess the extent to which pain relief in chronic back and leg pain (CBLP) following spinal cord stimulation (SCS) is influenced by patient-related factors, including pain location, and technology factors. A number of electronic databases were searched with citation searching of included papers and recent systematic reviews. All study designs were included. The primary outcome was pain relief following SCS, we also sought pain score (pre- and post-SCS). Multiple predictive factors were examined: location of pain, history of back surgery, initial level of pain, litigation/worker's compensation, age, gender, duration of pain, duration of follow-up, publication year, continent of data collection, study design, quality score, method of SCS lead implant, and type of SCS lead. Between-study association in predictive factors and pain relief were assessed by meta-regression. Seventy-four studies (N = 3,025 patients with CBLP) met the inclusion criteria; 63 reported data to allow inclusion in a quantitative analysis. Evidence of substantial statistical heterogeneity (P < 0.0001) in level of pain relief following SCS was noted. The mean level of pain relief across studies was 58% (95% CI: 53% to 64%, random effects) at an average follow-up of 24 months. Multivariable meta-regression analysis showed no predictive patient or technology factors. SCS was effective in reducing pain irrespective of the location of CBLP. This review supports SCS as an effective pain relieving treatment for CBLP with predominant leg pain with or without a prior history of back surgery. Randomized controlled trials need to confirm the effectiveness and cost-effectiveness of SCS in the CLBP population with predominant low back pain.This study was sponsored by Medtronic, Inc

Board Roles in Nonprofit Sport Organisations with a Dual Board System

Governance is a critical component of the effective management of a nonprofit sport organisation. Boards in this governance system play an important role to guide their organisations. While a number of agencies have provided documents of what boards should perform in their organisations, these documents remain descriptive. Empirical research on board roles particularly in a dual board system has been deficient. The purpose of this research therefore was to empirically investigate board roles in nonprofit sport organisations with a dual board system in Taiwan. 158 directors and 103 supervisors from 24 nonprofit sport organisations completed questionnaire regarding board roles. Two factor analyses were conducted. A 20-variable/4-factor scale of roles of directors and a 9-variable/2-factor scale of roles of supervisors were generated. Several conclusions were made based on results of this stud

Changes in the severity and subtype of Guillain-Barré syndrome admitted to a specialist Neuromedical ICU over a 25 year period

We report a retrospective review of 110 patients with acute Guillain-Barré syndrome (GBS) admitted to a specialised intensive care unit (ICU) in a tertiary referral centre over a 25 year period, the start of which coincided with the widespread introduction of plasma exchange (PE) and intravenous immunoglobulin (IVIG). The results were analysed by comparing 52 patients admitted in the first decade (1991-2000; Group 1) with 58 patients admitted between 2001-2014 (Group 2). Patients in both groups were comparable with respect to age and sex, and had a similar incidence and range of ICU complications. They received a comparable range of immunomodulatory treatments including IVIG and PE. However, the delay from presentation to referral to the tertiary ICU was longer in patients in Group 2. They also required mechanical ventilation for a longer duration, and had longer ICU and hospital stays. In Group 2, there was a higher incidence of axonal neuropathy (51%, compared to 24% in Group 1). Despite the longer delay to referral, the prevalence of axonal neuropathy and the duration of ventilation, overall mortality showed a downward trend (Group 1: 13.5%; Group 2: 5.2%). There was no late mortality in either group after step-down to neuro-rehabilitation or following discharge home or to the referring hospital. The rehabilitation outcomes were similar. This data show a shift in the pattern of referral to a tertiary referral ICU between the first and second decades following the wider availability of IVIG and PE for the treatment of GBS. The possible causes and implications of these findings are discussed

Impact of the National Institute for Health and Care Excellence (NICE) guidance on medical technology uptake: analysis of the uptake of spinal cord stimulation in England 2008-2012.

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: The National Institute for Health and Care Excellence (NICE) Technology Appraisal Guidance on spinal cord stimulation (SCS) was published in 2008 and updated in 2012 with no change. This guidance recommends SCS as a cost-effective treatment for patients with neuropathic pain. OBJECTIVE: To assess the impact of NICE guidance by comparing SCS uptake in England pre-NICE (2008-2009) and post-NICE (2009-2012) guidance. We also compared the English SCS uptake rate with that of Belgium, the Netherlands, France and Germany. DESIGN: SCS implant data for England was obtained from the Hospital Episode Statistics (HES) database and compared with other European countries where comparable data were available. RESULTS: The HES data showed small increases in SCS implantation and replacement/revision procedures, and a large increase in SCS trials between 2008 and 2012. The increase in the total number of SCS procedures per million of population in England is driven primarily by revision/replacements and increased trial activity. Marked variability in SCS uptake at both health regions and primary care trust level was observed. CONCLUSIONS: Despite the positive NICE recommendation for the routine use of SCS, we found no evidence of a significant impact on SCS uptake in England. Rates of SCS implantation in England are lower than many other European countries.Access to the QUANTIS database to extract the relevant Hospital Episode Statistics data was funded by Medtronic UK

True Neutrality as a New Type of Flavour

A classification of leptonic currents with respect to C-operation requires the separation of elementary particles into the two classes of vector C-even and axial-vector C-odd character. Their nature has been created so that to each type of lepton corresponds a kind of neutrino. Such pairs are united in families of a different C-parity. Unlike the neutrino of a vector type, any C-noninvariant Dirac neutrino must have his Majorana neutrino. They constitute the purely neutrino families. We discuss the nature of a corresponding mechanism responsible for the availability in all types of axial-vector particles of a kind of flavour which distinguishes each of them from others by a true charge characterized by a quantum number conserved at the interactions between the C-odd fermion and the field of emission of the corresponding types of gauge bosons. This regularity expresses the unidenticality of truly neutral neutrino and antineutrino, confirming that an internal symmetry of a C-noninvariant particle is described by an axial-vector space. Thereby, a true flavour together with the earlier known lepton flavour predicts the existence of leptonic strings and their birth in single and double beta decays as a unity of flavour and gauge symmetry laws. Such a unified principle explains the availability of a flavour symmetrical mode of neutrino oscillations.Comment: 19 pages, LaTex, Published version in IJT

Percutaneous pulmonary valve implantation in humans - Results in 59 consecutive patients

Background - Right ventricular outflow tract (RVOT) reconstruction with valved conduits in infancy and childhood leads to reintervention for pulmonary regurgitation and stenosis in later life.Methods and Results - Patients with pulmonary regurgitation with or without stenosis after repair of congenital heart disease had percutaneous pulmonary valve implantation (PPVI). Mortality, hemodynamic improvement, freedom from explantation, and subjective and objective changes in exercise tolerance were end points. PPVI was performed successfully in 58 patients, 32 male, with a median age of 16 years and median weight of 56 kg. The majority had a variant of tetralogy of Fallot (n = 36), or transposition of the great arteries, ventricular septal defect with pulmonary stenosis (n = 8). The right ventricular (RV) pressure (64.4 +/- 17.2 to 50.4 +/- 14 mm Hg, P < 0.001), RVOT gradient (33 +/- 24.6 to 19.5 +/- 15.3, P < 0.001), and pulmonary regurgitation ( PR) (grade 2 of greater before, none greater than grade 2 after, P < 0.001) decreased significantly after PPVI. MRI showed significant reduction in PR fraction (21 +/- 13% versus 3 +/- 4%, P < 0.001) and in RV end-diastolic volume (EDV) (94 +/- 28 versus 82 +/- 24 mL (.) beat(-1) (.) m(-2), P < 0.001) and a significant increase in left ventricular EDV ( 64 +/- 12 versus 71 +/- 13 mL (.) beat(-1.) m(-2), P = 0.005) and effective RV stroke volume ( 37 +/- 7 versus 42 +/- 9 mL (.) beat(-1) (.) m(-2), P = 0.006) in 28 patients (age 19 +/- 8 years). A further 16 subjects, on metabolic exercise testing, showed significant improvement in V(O2)max (26 +/- 7 versus 29 +/- 6 mL (.) kg(-1) (.) min(-1), P < 0.001). There was no mortality.Conclusions - PPVI is feasible at low risk, with quantifiable improvement in MRI-defined ventricular parameters and pulmonary regurgitation, and results in subjective and objective improvement in exercise capacity

The association between air travel and deep vein thrombosis: systematic review & meta-analysis.

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Air travel has been linked with the development of deep vein thrombosis (DVT) since the 1950s with a number of plausible explanations put forward for causation. No systematic review of the literature exploring this association has previously been published. METHODS: A comprehensive search was undertaken (Data bases searched were: MEDLINE, EMBASE, Cochrane Library) for studies that estimated both the incidence and the risk of DVT in air travellers relative to non-air travellers. RESULTS: In total 254 studies were identified but only six incidence studies and four risk studies met inclusion criteria justifying their use in a systematic review. Incidence of symptomatic DVT ranged from (0%) in one study to (0.28%) which was reported in pilots over ten years. The incidence of asymptomatic DVT ranged from (0%) to (10.34%). Pooled odds ratios for the two case control studies examining the risk of DVT following air travel were 1.11 (95% CI: 0.64-1.94). Pooled odds ratios for all models of travel including two studies of prolonged air travel (more than three hours) were 1.70 (95% CI: 0.89-3.22). CONCLUSION: We found no definitive evidence that prolonged (more than 3-hours) travel including air travel, increases the risk of DVT. There is evidence to suggest that flights of eight hours or more increase the risk of DVT if additional risk factors exist.All funding for this project came from the regional or national (UK) NHS

Meta-analyses of randomized controlled trials show suboptimal validity of surrogate outcomes for overall survival in advanced colorectal cancer

Comparative StudyMeta-AnalysisReviewValidation StudiesThis is the final version of the article. Available from Elsevier via the DOI in this record.OBJECTIVES: To quantify and compare the treatment effects on three surrogate end points, progression-free survival (PFS), time to progression (TTP), and tumor response rate (TR) vs. overall survival (OS) based on a meta-analysis of randomized controlled trials (RCTs) of drug interventions in advanced colorectal cancer (aCRC). STUDY DESIGN AND SETTING: We systematically searched for RCTs of pharmacologic therapies in aCRC between 2003 and 2013. Trial characteristics, risk of bias, and outcomes were recorded based on a predefined form. Univariate and multivariate random-effects meta-analyses were used to estimate pooled summary treatment effects. The ratio of hazard ratios (HRs)/odds ratios (ORs) and difference in medians were used to quantify the degree of difference in treatment effects on the surrogate end points and OS. Spearman ρ, surrogate threshold effect (STE), and R(2) were also estimated across predefined trial-level covariates. RESULTS: We included 101 RCTs. In univariate and multivariate meta-analyses, we found larger treatment effects for the surrogates than for OS. Compared with OS, treatment effects were on average 13% higher when HRs were measured and 3% to 45% higher when ORs were considered; differences in median PFS/TTP were higher than on OS by an average of 0.5 month. Spearman ρ ranged from 0.39 to 0.80, mean R(2) from 0.06 to 0.65, and STE was 0.8 for HRPFS, 0.64 for HRTTP, or 0.28 for ORTR. The stratified analyses revealed high variability across all strata. CONCLUSION: None of the end points in this study were found to achieve the level of evidence (ie, mean R(2)trial > 0.60) that has been set to select high or excellent correlation levels by common surrogate evaluation tools. Previous surrogacy relationships observed between PFS and TTP vs. OS in selected settings may not apply across other classes or lines of therapy

Health technology assessment of medical devices: a survey of non-European union agencies.

PublishedJournal ArticleResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from Cambridge University Press via the DOI in this record.OBJECTIVES: The aim of this study was to review and compare current health technology assessment (HTA) activities for medical devices across non-European Union HTA agencies. METHODS: HTA activities for medical devices were evaluated from three perspectives: organizational structure, processes, and methods. Agencies were primarily selected upon membership of existing HTA networks. The data collection was performed in two stages: stage 1-agency Web-site assessment using a standardized questionnaire, followed by review and validation of the collected data by a representative of the agency; and stage 2-semi-structured telephone interviews with key informants of a sub-sample of agencies. RESULTS: In total, thirty-six HTA agencies across twenty non-EU countries assessing medical devices were included. Twenty-seven of thirty-six (75 percent) agencies were judged at stage 1 to have adopted HTA-specific approaches for medical devices (MD-specific agencies) that were largely organizational or procedural. There appeared to be few differences in the organization, process and methods between MD-specific and non-MD-specific agencies. Although the majority (69 percent) of both categories of agency had specific methods guidance or policy for evidence submission, only one MD-specific agency had developed methodological guidelines specific to medical devices. In stage 2, many MD-specific agencies cited insufficient resources (budget, skilled employees), lack of coordination (between regulator and reimbursement bodies), and the inability to generalize findings from evidence synthesis to be key challenges in the HTA of medical devices. CONCLUSIONS: The lack of evidence for differentiation in scientific methods for HTA of devices raises the question of whether HTA needs to develop new methods for medical devices but rather adapt existing methodological approaches. In contrast, organizational and/or procedural adaptation of existing HTA agency frameworks to accommodate medical devices appear relatively commonplace.This study was supported by a research grant from the European Community’s Seventh Framework Program (FP7 - HEALTH Grant Agreement no. 305694). The sponsor had no role in the study design, collection and analysis of data, writing of the report, or submission of the paper for publication. The authors wish to thank all interviewees and agencies’ assessment forms verifiers for their invaluable contribution to the completion of this study