Spatial confinement of muonium atoms

We report the achievement of spatial confinement of muonium atoms (the bound state of a positive muon and an electron). Muonium emitted into vacuum from mesoporous silica reflects between two SiO$_2$ confining surfaces separated by 1 mm. From the data, one can extract that the reflection probability on the confining surfaces kept at 100 K is about 90% and the reflection process is well described by a cosine law. This technique enables new experiments with this exotic atomic system and is a very important step towards a measurement of the 1S-2S transition frequency using continuous wave laser spectroscopy.Comment: 5 pages, 6 figure

Enhanced Trabeculectomy: The Moorfields Safer Surgery System

Trabeculectomy with antifibrotic treatment is still the most popular incisional procedure for glaucoma filtration surgery (GFS) worldwide. The advent of antifibrotic agents reduced failure due to scarring but resulted in increased complications. Advances in trabeculectomy surgery have been driven by the need to minimise the risk of: (1) complications and (2) surgical failure. This chapter covers preoperative, intraoperative, and postoperative strategies, which improve the outcome of GFS. Strategies to reduce the risk of complications centre on the prevention of postoperative hypotony by minimising the risk of overdrainage, postoperative wound leaks, and poor bleb morphology. Surgical techniques to reduce the risk of postoperative fibrosis by the use of antifibrotic agents (including mitomycin C) are discussed in detail. These techniques are based on a combination of considerable clinical experience, observation, and laboratory research. The need to address pre-, intra-, and postoperative issues in each individual patient is emphasised. These changes are embodied in the system we call the "Moorfields Safer Surgery System." The use of these strategies has considerably reduced the incidence of major complications, including hypotony, cystic blebs, and endophthalmitis in practices around the world. Most of these techniques are simple, require minimal equipment, and can be easily mastered. They are associated with an improvement in overall outcome and it is hoped that this chapter will help the reader benefit from these advances

The interplay between inflammation, immunity and commensal microflora in glaucomatous neurodegeneration

This investigation sheds some light on intersecting mechanistic pathways in glaucomatous neurodegeneration. Progressive degeneration of retinal ganglion cells (RGCs) resulting in optic nerve head cupping and visual loss are characteristic features of glaucoma. The pathophysiological causes of this degeneration are not clearly defined but most certainly involves multifactorial and polygenic mechanisms. Large genome-wide association studies suggest a role of angiopoietin-receptor tyrosine kinase signalling, lipid metabolism, mitochondrial function, and developmental processes as underlying risks for elevated intraocular pressure (IOP) and primary open angle glaucoma (POAG)(8). Although age and raised IOP remain the most prominent risk factors for glaucoma, disease phenotypes of normal tension glaucoma suggest mechanisms beyond pressure-mediated neurodegeneration

Sociodemographic and lifestyle predictors of incident hospital admissions with multimorbidity in a general population, 1999-2019: the EPIC-Norfolk cohort.

BACKGROUND:The ageing population and prevalence of long-term disorders with multimorbidity are a major health challenge worldwide. The associations between comorbid conditions and mortality risk are well established; however, few prospective community-based studies have reported on prior risk factors for incident hospital admissions with multimorbidity. We aimed to explore the independent associations for a range of demographic, lifestyle and physiological determinants and the likelihood of subsequent hospital incident multimorbidity. METHODS:We examined incident hospital admissions with multimorbidity in 25 014 men and women aged 40-79 in a British prospective population-based study recruited in 1993-1997 and followed up until 2019. The determinants of incident multimorbidity, defined as Charlson Comorbidity Index ≥3, were investigated using multivariable logistic regression models for the 10-year period 1999-2009 and repeated with independent measurements in a second 10-year period 2009-2019. RESULTS:Between 1999 and 2009, 18 179 participants (73% of the population) had a hospital admission. Baseline 5-year and 10-year incident multimorbidities were observed in 6% and 12% of participants, respectively. Age per 10-year increase (OR 2.19, 95% CI 2.06 to 2.33) and male sex (OR 1.32, 95% CI 1.19 to 1.47) predicted incident multimorbidity over 10 years. In the subset free of the most serious diseases at baseline, current smoking (OR 1.86, 95% CI 1.60 to 2.15), body mass index >30 kg/m² (OR 1.48, 95% CI 1.30 to 1.70) and physical inactivity (OR 1.16, 95% CI 1.04 to 1.29) were positively associated and plasma vitamin C (a biomarker of plant food intake) per SD increase (OR 0.86, 95% CI 0.81 to 0.91) inversely associated with incident 10-year multimorbidity after multivariable adjustment for age, sex, social class, education, alcohol consumption, systolic blood pressure and cholesterol. Results were similar when re-examined for a further time period in 2009-2019. CONCLUSION:Age, male sex and potentially modifiable lifestyle behaviours including smoking, body mass index, physical inactivity and low fruit and vegetable intake were associated with increased risk of future incident hospital admissions with multimorbidity

Fc-fusion mimetics

The Fc-fusion mimetic RpR 2 was prepared by disulfide bridging conjugation using a PEG in the place of the Fc. RpR 2 displayed higher affinity for VEGF than aflibercept caused primarily by a slower dissociation rate, which can prolong a drug at its site of action. RpRs have considerable potential for development as stable, organ specific therapeutics

Dual acting therapeutic proteins for intraocular use

Antibody-based medicines that target vascular endothelial growth factor (VEGF) are administered by intravitreal injection to treat chronic neovascular retinal diseases. Much ongoing effort is focused on enhancing therapeutic outcome of these medicines. One strategy is the use of dual acting drugs (e.g. bispecific antibodies) to simultaneously bind to more than one intraocular biological target. A dual acting molecule targeting components within the vitreal cavity could also potentially extend vitreous residence time. In this review, the applications of bispecific antibodies within the eye are described with consideration to potential targets, applications and suitable bispecific formats

Residential area deprivation and risk of subsequent hospital admission in a British population: the EPIC-Norfolk cohort.

OBJECTIVES:To investigate whether residential area deprivation index predicts subsequent admissions to hospital and time spent in hospital independently of individual social class and lifestyle factors. DESIGN:Prospective population-based study. SETTING:The European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) study. PARTICIPANTS:11 214 men and 13 763 women in the general population, aged 40-79 years at recruitment (1993-1997), alive in 1999. MAIN OUTCOME MEASURE:Total admissions to hospital and time spent in hospital during a 19-year time period (1999-2018). RESULTS:Compared to those with residential Townsend Area Deprivation Index lower than the average for England and Wales, those with a higher than average deprivation index had a higher likelihood of spending >20 days in hospital multivariable adjusted OR 1.18 (95% CI 1.07 to 1.29) and having 7 or more admissions OR 1.11 (95% CI 1.02 to 1.22) after adjustment for age, sex, smoking status, education, social class and body mass index. Occupational social class and educational attainment modified the association between area deprivation and hospitalisation; those with manual social class and lower education level were at greater risk of hospitalisation when living in an area with higher deprivation index (p-interaction=0.025 and 0.020, respectively), while the risk for non-manual and more highly educated participants did not vary greatly by area of residence. CONCLUSION:Residential area deprivation predicts future hospitalisations, time spent in hospital and number of admissions, independently of individual social class and education level and other behavioural factors. There are significant interactions such that residential area deprivation has greater impact in those with low education level or manual social class. Conversely, higher education level and social class mitigated the association of area deprivation with hospital usage

Structural and electrical properties of bismuth magnesium tantalate pyrochlores.

The subsolidus cubic pyrochlore phases in the Bi2O3–MgO–Ta2O5 (BMT) system were prepared with the proposed formula, Bi3+(5/2)xMg2−xTa3−(3/2)xO14−x (0.12 ≤ x ≤ 0.22). Replacement of smaller cations, Mg2+ and Ta5+ by larger Bi3+ cations with considerable oxygen non-stoichiometry within structure was proposed. The synthesised samples were confirmed phase pure by X-ray powder diffraction and their refined lattice parameters were in the range of 10.5532(4)–10.5672(9) Å. The grain sizes of the samples determined by SEM analysis were in the range of 0.6–10.60 μm and their average relative densities were more than 80%. Five infrared-active modes were also observed in their FTIR spectra due to their metalsingle bondoxygen bonds. The BMT pyrochlores were highly electrical resistive with high dielectric constants, ɛ′ in the range of ∼70–85; dielectric losses, tan δ in the order of 10−3 at frequency 1 MHz and a negative temperature coefficient of permittivities, TCɛ′ of ∼−158 to −328 ppm/°C

The Association of Ambient Air Pollution With Cataract Surgery in UK Biobank Participants: Prospective Cohort Study

Purpose: Air pollution is associated with chronic diseases of later life. Cataract is the most common cause of blindess globally. It is biologically plausible that cataract risk is increased by pollution exposure. Therefore, the relationship between air pollution and incident cataract surgery was examined. Methods: This was a prospective, observational study involving 433,727 UK Biobank participants. Ambient air pollution measures included particulates, nitrogen dioxide (NO2) and nitrogen oxides (NOx). Outdoor air pollution was estimated based on land use regression models. Participants undergoing cataract surgery in either eye were ascertained via data linkage to the National Health Service procedure statistics. Those undergoing cataract surgery within 1 year of baseline assessment and those reporting cataract at baseline were excluded. Cox proportional hazards models were used to examine the associations between air pollutants and incident cataract surgery, adjusting for sociodemographic and lifestyle factors. Results: There were 16,307 incident cases of cataract surgery. Higher exposure to PM2.5 was associated with a 5% increased risk of incident cataract surgery (per interquartile range [IQR] increase). Compared to the lowest quartile, participants with exposures to PM2.5, NO2, and NOx in the highest quartile were 14%, 11%, and 9% more likely to undergo cataract surgery, respectively. A continuous exposure-response relationship was observed, with the likelihood of undergoing cataract surgery being progressively higher with greater levels of PM2.5, NO2, and NOx (P for trend P < 0.001). Conclusions: Although the results of our study showed a 5% increased risk of future cataract surgery following an exposure to PM2.5, NO2, and NOx, the effect estimates were relatively small. Further research is required to determine if the associations identified are causal