The Problem of Political Credibility: Epistemic Realism and Cautious Liberalism

In this dissertation, I transform the problem of political authority into the problem of political credibility. In my terminology, credible political authorities satisfy the “confidence tenet,” which requires that the public can become reasonably confident that political authorities are legitimate. So, I defend a new type of realism “epistemic realism.” A conception of legitimacy should concede to the epistemic limits of reasonable citizens. It should avoid normative political principles that reasonable citizens will probably never become reasonably confident that political authorities do satisfy. In search of political credibility, I argue against “highly moralised” conceptions of legitimacy that make legitimacy depend on promoting justice in some sense. In particular, I primarily argue against the political theorist David Estlund’s epistemic proceduralism. Estlund says liberal democratic states are legitimate political authorities because democratic mechanisms are fair or otherwise reasonably acceptable procedures and democratic decisions publicly reveal what promotes justice and the common good. However, I argue that epistemic proceduralism makes liberal democratic states lack credible political authority because reasonable citizens should lack confidence in whether democratic decisions do publicly reveal what promotes justice and the common good and if democratic mechanisms are fair procedures. In search of a solution, I introduce “cautious liberalism.” A cautious conception of legitimacy prioritises avoiding harm over promoting justice for primarily epistemic reasons. Reasonable citizens can become reasonably confident liberal democratic states do avoid harm in some sense. In particular, a “peaceful instrumentalist” conception of legitimacy makes legitimacy depend on the preservation of a mutually beneficial peace. Liberal democratic states can become credible political authorities that reasonable citizens are reasonably confident are legitimate with peaceful instrumentalism. Reasonable citizens can publicly observe that liberal democratic states tend to make the vote remain more politically attractive than the pitchfork

Evaluation of the strategic positioning of IOC-UNESCO

he Intergovernmental Oceanographic Commission (IOC-UNESCO) has functional autonomy within UNESCO. It is the only UN body specializing exclusively in ocean science, ocean observation, ocean data and information exchange and dedicated ocean services such as Tsunami Early Warning Systems. In 2019, UNESCO’s Intergovernmental Oceanographic Commission was tasked to lead the UN Decade of the Ocean. This opportunity, combined with a fast-evolving ecosystem of international actors in an expanding and increasingly crowded ocean policy and marine science space, prompted IOC-UNESCO to request an evaluation of IOC-UNESCO with a focus on its strategic positioning within the UN system and the broader landscape of ocean-related actors and programmes to meet the high demand for sound ocean science in an oceanographic space. The evaluation found that IOC-UNESCO is a valued partner for Member States as well as other international and national actors, and indispensable for strengthening capacities and providing the data and technical information on ocean science policy that serves as a basis for national level data. IOC-UNESCO has been most successful in providing contributions to UN Frameworks and Conventions (e.g. UNFCCC, Sendai and CBD), in acting as a neutral platform to discuss the increasingly relevant issue of ocean health and climate change, in bringing Member States together and fostering exchanges between governments and scientists, as well as in providing to the extended oceanographic community access to data, information and science. However, strategic advocacy at the national level, engagement at the regional level, and resourcing and visibility of gender equality and women’s empowerment in the ocean space within and outside IOC-UNESCO are among the areas where further improvements are required. The establishment of the Decade of Ocean Science for Sustainable Development is the most important strategic institutional achievement of IOC-UNESCO in recent years. It is an important opportunity, but the absence of a clearly defined results framework and inadequate resources could jeopardize its success. Furthermore, it still needs to be determined how to best exploit IOC-UNESCO’s data and knowledge base and how UNESCO can best support the Decade, among other through intersectoral work

Attitudes of pregnant women and healthcare professionals towards clinical trials and routine implementation of antenatal vaccination against respiratory syncytial virus : a multicenter questionnaire study

Introduction: Respiratory syncytial virus (RSV) is a common cause of infant hospitalization and mortality. With multiple vaccines in development, we aimed to determine: (1) the awareness of RSV among pregnant women and healthcare professionals (HCPs), and (2) attitudes toward clinical trials and routine implementation of antenatal RSV vaccination.Methods: Separate questionnaires for pregnant women and HCPs were distributed within 4 hospitals in South England (July 2017–January 2018).Results: Responses from 314 pregnant women and 204 HCPs (18% obstetricians, 75% midwives, 7% unknown) were analyzed. Most pregnant women (88%) and midwives (66%) had no/very little awareness of RSV, unlike obstetricians (14%). Among pregnant women, 29% and 75% would likely accept RSV vaccination as part of a trial, or if routinely recommended, respectively. Younger women (16–24 years), those of 21–30 weeks’ gestation, and with experience of RSV were significantly more likely to participate in trials [odds ratio (OR): 1.42 (1.72–9.86); OR: 2.29 (1.22–4.31); OR: 9.07 (1.62–50.86), respectively]. White-British women and those of 21–30 weeks’ gestation were more likely to accept routinely recommended vaccination [OR: 2.16 (1.07–4.13); OR: 2.10 (1.07–4.13)]. Obstetricians were more likely than midwives to support clinical trials [92% vs. 68%, OR: 2.50 (1.01–6.16)] and routine RSV vaccination [89% vs. 79%, OR: 4.08 (1.53–9.81)], as were those with prior knowledge of RSV, and who deemed it serious.Conclusions: RSV awareness is low among pregnant women and midwives. Education will be required to support successful implementation of routine antenatal vaccination. Research is needed to understand reasons for vaccine hesitancy among pregnant women and HCPs, particularly midwives.<br/

The impact of bone mineral density and disc degeneration on shear strength and stiffness of the lumbar spine following laminectomy

Purpose Laminectomy is a standard surgical procedure for elderly patients with symptomatic degenerative lumbar stenosis. The procedure aims at decompression of the affected nerves, but it also causes a reduction of spinal shear strength and shear stiffness. The magnitude of this reduction and the influence of bone mineral density (BMD) and disc degeneration are unknown. We studied the influence of laminectomy, BMD, and disc degeneration on shear force to failure (SFF) and shear stiffness (SS). Methods Ten human cadaveric lumbar spines were obtained (mean age 72.1 years, range 53-89 years). Laminectomy was performed either on L2 or L4, equally divided within the group of ten spines. BMD was assessed by dual X-ray absorptiometry (DXA). Low BMD was defined as a BMD value below the median. Intervertebral discs were assessed for degeneration by MRI (Pfirrmann) and scaled in mild and severe degeneration groups. Motion segments L2-L3 and L4-L5 were isolated from each spine. SFF and SS were measured, while loading simultaneously with 1,600 N axial compression. Results Low BMD had a significant negative effect on SFF. In addition, a significant interaction between low BMD and laminectomy was found. In the high BMD group, SFF was 2,482 N (range 1,678-3,284) and decreased to 1,371 N (range 940-1,886) after laminectomy. In the low BMD group, SFF was 1,339 N (range 909-1,628) and decreased to 761 N (range 561-1,221). Disc degeneration did not affect SFF, nor did it interact with laminectomy. Neither low BMD nor the interaction of low BMD and laminectomy did affect SS. Degeneration and its interaction with laminectomy did not significantly affect SS. Conclusions In conclusion, low BMD significantly decreased SFF before and after lumbar laminectomy. Therefore, DXA assessment may be an important asset to preoperative screening. Lumbar disc degeneration did not affect shear properties of lumbar segments before or after laminectomy. © 2012 Springer-Verlag

Anterior shear strength of the porcine lumbar spine after laminectomy and partial facetectomy

Degenerative lumbar spinal stenosis is the most common reason for lumbar surgery in patients in the age of 65 years and older. The standard surgical management is decompression of the spinal canal by laminectomy and partial facetectomy. The effect of this procedure on the shear strength of the spine has not yet been investigated in vitro. In the present study we determined the ultimate shear force to failure, the displacement and the shear stiffness after performing a laminectomy and a partial facetectomy. Eight lumbar spines of domestic pigs (7 months old) were sectioned to obtain eight L2–L3 and eight L4–L5 motion segments. All segments were loaded with a compression force of 1,600 N. In half of the 16 motion segments a laminectomy and a 50% partial facetectomy were applied. The median ultimate shear force to failure with laminectomy and partial facetectomy was 1,645 N (range 1,066–1,985) which was significantly smaller (p = 0.012) than the ultimate shear force to failure of the control segments (median 2,113, range 1,338–2,659). The median shear stiffness was 197.4 N/mm (range 119.2–216.7) with laminectomy and partial facetectomy which was significantly (p = 0.036) smaller than the stiffness of the control specimens (median 216.5, 188.1–250.2). It was concluded that laminectomy and partial facetectomy resulted in 22% reduction in ultimate shear force to failure and 9% reduction in shear stiffness. Although relatively small, these effects may explain why patients have an increased risk of sustaining shear force related vertebral fractures after spinal decompression surgery

Cost-effectiveness of replacing versus discarding the nail in children with nail bed injury

Every year in the UK, around 10 000 children need to have operations to mend injuries to the bed of their fingernails. Currently, most children have their fingernail placed back on the injured nail bed after the operation. The NINJA trial found that children were slightly less likely to have an infection if the nail was thrown away rather than being put back, but the difference between groups was small and could have be due to chance. This study looked at whether replacing the nail is cost-effective compared with throwing it away. Using data from the NINJA trial, we compared costs, healthcare use, and quality of life and assessed the cost-effectiveness of replacing the nail. It was found that throwing the nail away after surgery would save the National Health Service (NHS) £75 (€85) per operation compared with placing the nail back on the nail bed. Changing clinical practice could save the NHS in England £720 000 (€819 000) per year

Effectiveness of nail bed repair in children with or without replacing the fingernail : NINJA multicentre randomized clinical trial

Background Surgery for nail bed injuries in children is common. One of the key surgical decisions is whether to replace the nail plate following nail bed repair. The aim of this RCT was to assess the clinical effectiveness and cost-effectiveness of nail bed repair with fingernail replacement/substitution compared with repair without fingernail replacement. Methods A two-arm 1 : 1 parallel-group open multicentre superiority RCT was performed across 20 secondary-care hospitals in the UK. The co-primary outcomes were surgical-site infection at around 7 days after surgery and cosmetic appearance summary score at a minimum of 4 months. Results Some 451 children presenting with a suspected nail bed injury were recruited between July 2018 and July 2019; 224 were allocated to the nail-discarded arm, and 227 to the nail-replaced arm. There was no difference in the number of surgical-site infections at around 7 days between the two interventions or in cosmetic appearance. The mean total healthcare cost over the 4 months after surgery was €84 (95 per cent c.i. 34 to 140) lower for the nail-discarded arm than the nail-replaced arm (P < 0.001). Conclusion After nail bed repair, discarding the fingernail was associated with similar rates of infection and cosmesis ratings as replacement of the finger nail, but was cost saving

Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002)

Background COVID-19 vaccine supply shortages are causing concerns about compromised immunity in some countries as the interval between the first and second dose becomes longer. Conversely, countries with no supply constraints are considering administering a third dose. We assessed the persistence of immunogenicity after a single dose of ChAdOx1 nCoV-19 (AZD1222), immunity after an extended interval (44–45 weeks) between the first and second dose, and response to a third dose as a booster given 28–38 weeks after the second dose. Methods In this substudy, volunteers aged 18–55 years who were enrolled in the phase 1/2 (COV001) controlled trial in the UK and had received either a single dose or two doses of 5 × 1010 viral particles were invited back for vaccination. Here we report the reactogenicity and immunogenicity of a delayed second dose (44–45 weeks after first dose) or a third dose of the vaccine (28–38 weeks after second dose). Data from volunteers aged 18–55 years who were enrolled in either the phase 1/2 (COV001) or phase 2/3 (COV002), single-blinded, randomised controlled trials of ChAdOx1 nCoV-19 and who had previously received a single dose or two doses of 5 × 1010 viral particles are used for comparison purposes. COV001 is registered with ClinicalTrials.gov, NCT04324606, and ISRCTN, 15281137, and COV002 is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137, and both are continuing but not recruiting. Findings Between March 11 and 21, 2021, 90 participants were enrolled in the third-dose boost substudy, of whom 80 (89%) were assessable for reactogenicity, 75 (83%) were assessable for evaluation of antibodies, and 15 (17%) were assessable for T-cells responses. The two-dose cohort comprised 321 participants who had reactogenicity data (with prime-boost interval of 8–12 weeks: 267 [83%] of 321; 15–25 weeks: 24 [7%]; or 44–45 weeks: 30 [9%]) and 261 who had immunogenicity data (interval of 8–12 weeks: 115 [44%] of 261; 15–25 weeks: 116 [44%]; and 44–45 weeks: 30 [11%]). 480 participants from the single-dose cohort were assessable for immunogenicity up to 44–45 weeks after vaccination. Antibody titres after a single dose measured approximately 320 days after vaccination remained higher than the titres measured at baseline (geometric mean titre of 66·00 ELISA units [EUs; 95% CI 47·83–91·08] vs 1·75 EUs [1·60–1·93]). 32 participants received a late second dose of vaccine 44–45 weeks after the first dose, of whom 30 were included in immunogenicity and reactogenicity analyses. Antibody titres were higher 28 days after vaccination in those with a longer interval between first and second dose than for those with a short interval (median total IgG titre: 923 EUs [IQR 525–1764] with an 8–12 week interval; 1860 EUs [917–4934] with a 15–25 week interval; and 3738 EUs [1824–6625] with a 44–45 week interval). Among participants who received a third dose of vaccine, antibody titres (measured in 73 [81%] participants for whom samples were available) were significantly higher 28 days after a third dose (median total IgG titre: 3746 EUs [IQR 2047–6420]) than 28 days after a second dose (median 1792 EUs [IQR 899–4634]; Wilcoxon signed rank test p=0·0043). T-cell responses were also boosted after a third dose (median response increased from 200 spot forming units [SFUs] per million peripheral blood mononuclear cells [PBMCs; IQR 127–389] immediately before the third dose to 399 SFUs per milion PBMCs [314–662] by day 28 after the third dose; Wilcoxon signed rank test p=0·012). Reactogenicity after a late second dose or a third dose was lower than reactogenicity after a first dose. Interpretation An extended interval before the second dose of ChAdOx1 nCoV-19 leads to increased antibody titres. A third dose of ChAdOx1 nCoV-19 induces antibodies to a level that correlates with high efficacy after second dose and boosts T-cell responses. Funding UK Research and Innovation, Engineering and Physical Sciences Research Council, National Institute for Health Research, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research Oxford Biomedical Research Centre, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Thames Valley and South Midlands NIHR Clinical Research Network, AstraZeneca, and Wellcome

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.

BACKGROUND: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. METHODS: We present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 1010 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). FINDINGS: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4-74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3-85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59-0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3-91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0-69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18-55 years (GMR 2·32 [2·01-2·68]). INTERPRETATION: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose. FUNDING: UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca