Some aspects of the editorial policy of L'Avenir from 16 October 1830 to 15 November 1831

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Learning for life:educational provision at Cadbury, 1831-1981

Cadbury showed concern for the welfare of its labour force in a variety of ways and not least in the provision of educational and educative-recreational facilities. The firm regarded the education of employees as having a positive effect on the efficiency of the business at the same time as being of benefit to the individual, the local community and the nation. The life-long education of people was seen as essential for personal fulfilament, social improvement, economic competitiveness and the proper functioning of democratic procedures. The educational system built up at Cadbury, and the philosophy on which it was founded, acquired both a domestic and international reputation. Its main components were the day continuation education of juniors; the Bournville Works Evening Institute; vocational and non-vocational scholarships; emphasis on the primary importance of general education as a basis for life, work and technical training; stress on equality of educational opportunity for females; and leisure and sporting amenities which the firm felt to be educative in the sense that they contributed to personal psychological and physical development and social skills. The system was primarily shaped and constructed in the first three decades of the twentieth century and went into decline and eventual demise in the 1960's and 1970's as a result of economic pressures, social changes, enhanced state arrangements for education, shifts in Cadbury management thinking and the merger with Schweppes in 1969.

Ranibizumab versus Bevacizumab to treat neovascular age-related macular degeneration:one-year findings from the IVAN Randomized Trial

PURPOSE: To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration (nAMD). DESIGN: Multicenter, noninferiority factorial trial with equal allocation to groups. The noninferiority limit was 3.5 letters. This trial is registered (ISRCTN92166560). PARTICIPANTS: People >50 years of age with untreated nAMD in the study eye who read =25 letters on the Early Treatment Diabetic Retinopathy Study chart. METHODS: We randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with monthly review. MAIN OUTCOME MEASURES: The primary outcome is at 2 years; this paper reports a prespecified interim analysis at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure. Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion morphology, serum vascular endothelial growth factor (VEGF) levels, and costs. RESULTS: Between March 27, 2008 and October 15, 2010, we randomized and treated 610 participants. One year after randomization, the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab -1.99 letters, 95% confidence interval [CI], -4.04 to 0.06). Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous -0.35 letters; 95% CI, -2.40 to 1.70). Foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI, 0.86 to 0.97; P = 0.005). Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; P = 0.03). There was no difference between drugs in the proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; P = 0.25). Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P

Changes in intraocular pressure in study and fellow eyes in the IVAN trial

PURPOSE: To describe changes in intraocular pressure (IOP) in the 'alternative treatments to Inhibit VEGF in Age-related choroidal Neovascularisation (IVAN)' trial (registered as ISRCTN92166560). DESIGN: Randomised controlled clinical trial with factorial design. PARTICIPANTS: Patients (n=610) with treatment naïve neovascular age-related macular degeneration were enrolled and randomly assigned to receive either ranibizumab or bevacizumab and to two regimens, namely monthly (continuous) or as needed (discontinuous) treatment. METHODS: At monthly visits, IOP was measured preinjection in both eyes, and postinjection in the study eye. OUTCOME MEASURES: The effects of 10 prespecified covariates on preinjection IOP, change in IOP (postinjection minus preinjection) and the difference in preinjection IOP between the two eyes were examined. RESULTS: For every month in trial, there was a statistically significant rise in both the preinjection IOP and the change in IOP postinjection during the time in the trial (estimate 0.02 mm Hg, 95% CI 0.01 to 0.03, p<0.001 and 0.03 mm Hg, 95% CI 0.01 to 0.04, p=0.002, respectively). There was also a small but significant increase during the time in trial in the difference in IOP between the two eyes (estimate 0.01 mm Hg, 95% CI 0.005 to 0.02, p<0.001). There were no differences between bevacizumab and ranibizumab for any of the three outcomes (p=0.93, p=0.22 and p=0.87, respectively). CONCLUSIONS: Anti-vascular endothelial growth factor agents induce increases in IOP of small and uncertain clinical significance.