What are the priorities for improving cataract surgical outcomes in Africa? Results of a Delphi exercise.

PURPOSE: The quality of cataract surgery delivered in sub-Saharan Africa (SSA) is a significant constraint to achieving the elimination of avoidable blindness. No published reports from routine SSA cataract services attain the WHO benchmarks for visual outcomes; poor outcomes (<6/60) often comprise 20% in published case series. This Delphi exercise aimed to identify and prioritise potential interventions for improving the quality of cataract surgery in SSA to guide research and eye health programme development. METHODS: An initial email open-question survey created a ranked list of priorities for improving quality of surgical services. A second-round face-to-face discussion facilitated at a Vision 2020 Research Mentorship Workshop in Tanzania created a refined list for repeated ranking. RESULTS: Seventeen factors were agreed that might form target interventions to promote quality of cataract services. Improved training of surgeons was the top-ranked item, followed by utilisation of biometry, surgical equipment availability, effective monitoring of outcomes of cataract surgery by the surgeon, and well-trained support staff for the cataract pathway (including nurses seeing post-operative cases). CONCLUSION: Improving the quality of cataract surgery in SSA is a clinical, programmatic and public health priority. In the absence of other evidence, the collective expert opinion of those involved in ophthalmic services regarding the ranking of factors to promote quality improvement, refined through this Delphi exercise, provides us with candidate intervention areas to be evaluated

The simulated ocular surgery (SOS) trials: randomised-controlled trials comparing intense simulation-based surgical edication for cataract and glaucoma surgery to conventional training alone in East and Southern Africa

Cataract remains the most common cause of blindness globally, and glaucoma is the third after uncorrected refractive error. Surgical management remains a priority, yet surgical training of ophthalmologists continues in the outdated apprentice model. Simulation-based surgical education is yet to be tested to the level of a randomised-controlled trial in ophthalmology. We designed two separate and independent multi-centre multi-country investigator-masked randomised controlled educational-intervention parallel group efficacy trials. Post-graduate doctors in ophthalmology training programmes at collaborating institutions in five East and Southern African countries were assessed for eligibility for inclusion (not having performed the procedure as primary surgeon) into either the OLIMPICS (ophthalmic learning and improvement initiative in cataract surgery) or GLASS (glaucoma simulated surgery) trials. Fifty-one surgical trainees were recruited into the GLASS trial, and 50 into the OLIMPICS trial. Surgical competency was assessed by video recordings, which were double marked by independent experts who were masked to group assignment and timing of the assessment. The intervention was an intense simulation-based cataract or glaucoma surgical training course over 5 days. Primary outcome measure was surgical competency at three-months assessed with validated simulated surgical competency assessment rubrics, the Sim-OSSCARs (ophthalmic simulation surgical competency assessment rubric), for both trials. The trials were registered in March 2017 on the Pan-African Clinical Trial Registry (PACTR201803002159198) and are currently closed to recruitment. Baseline characteristics of age, sex, year of training, baseline knowledge and competency scores were balanced between both arms, for both trials. In total 1,361 surgical videos from across different time-points were independently graded by two separate graders in both trials. In the OLIMPICS trial, 50 participants were recruited between November 2017 and May 2018 and 49 included in the final intention-to-treat analysis with one dropout from the control group. Intervention group participants increased mean simulated surgical competence scores from a baseline of 10.8 of 40 points (27.0%) to 33.7 (84.2%) at 3-months after the training intervention, an increase of 212%. Control group participants’ mean baseline scores were 12.8 (31.9%) and 3-month scores 17.9 (44.7%). We found strong evidence (linear regression p<0.0001) that those in the intervention arm were estimated to have higher scores at three months than those in the control arm, after adjusting for baseline score. Among individuals with the same baseline score, those who received the training were estimated to have scores 16.6 points higher (95%CI 14.5 to 18.8) at three months, compared to those who had not received the training. Intervention participants performed a mean of 22 cataract surgeries as primary surgeon in the one year following the training intervention, compared to 9 by control participants (Poisson regression p<0.0001). Surgical complications were reported for the one year period, and posterior capsule rupture (PCR) rates were 7.4% for the intervention group compared to 26.2% for controls (p<0.0001). Confidence rating scores were assessed using a ten-point Likert scale anchored at 1=’not confident at all’, and 10=’very confident’. Confidence as cataract surgeons increased from 2.2 (of 10) to 6.3 at three-months in the intervention group, compared to 3.4 at baseline to 4.2 for the control group. Among individuals with the same baseline confidence score, those receiving the training were estimated to have scores 2.7 points higher (95%CI 1.6 to 3.7) (p<0.001). In the GLASS trial, 53 trainee ophthalmologists were assessed for eligibility, and 51 were enrolled and randomised. Forty-nine participants were included in the final intention-to-treat analysis: 23 intervention and 26 control, following two drop outs from the intervention group. Baseline surgical competency scores for intervention were a mean of 9.1/40 (22.6%) [median 7.3, IQR 5.4-12.1]; and for control: 8.7/40 (21.8%) [median 8.2, IQR 6.3-12.0] participants. Mean Sim-OSSCAR scores at three-months were 30.4 (76.1%) [median 30.3 IQR 27.8-33.5] and 9.8 (24.4%) [median 9.2 IQR 7.5-11.7] for intervention and control groups respectively. We found strong evidence (linear regression p<0.0001) that those in the intervention arm were estimated to have higher scores at three months than those in the control arm, after adjusting for baseline score as a fixed effect. Among individuals with the same baseline score, those who received the training were estimated to have scores 20.5 points (of 40) higher (95%CI 18.4 to 22.6) at three months, compared to those who had not received the training (linear regression p<0.0001). Baseline mean self-reported confidence in glaucoma surgical skills was 3.0/10 for intervention and 3.2 for control participants. This increased to mean 6.4 and 3.7 at three months respectively (p=0.002). Trainee participants in the intervention group performed a mean of 3.1 live surgical trabeculectomies as primary surgeon over one year following training (median 2, range 0-15, IQR 0-4). Over the same period (and before their simulation training) the control group performed a mean of 0.15 (only one of the 26 control participants performed any glaucoma surgery, compared to 14 of the 23 intervention participants). These are the first multi-centre ophthalmic simulation surgery educational-intervention randomised controlled trials ever conducted. Intense simulation training affords a rapid and sustained increase in surgical competence, confidence as a surgeon, and impacts the number of live surgeries performed. Simulation education in cataract surgery affords a striking benefit in terms of patient safety

Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism.

Recent studies have identified both recessive and dominant forms of mitochondrial disease that result from ATAD3A variants. The recessive form includes subjects with biallelic deletions mediated by non-allelic homologous recombination. We report five unrelated neonates with a lethal metabolic disorder characterized by cardiomyopathy, corneal opacities, encephalopathy, hypotonia, and seizures in whom a monoallelic reciprocal duplication at the ATAD3 locus was identified. Analysis of the breakpoint junction fragment indicated that these 67 kb heterozygous duplications were likely mediated by non-allelic homologous recombination at regions of high sequence identity in ATAD3A exon 11 and ATAD3C exon 7. At the recombinant junction, the duplication allele produces a fusion gene derived from ATAD3A and ATAD3C, the protein product of which lacks key functional residues. Analysis of fibroblasts derived from two affected individuals shows that the fusion gene product is expressed and stable. These cells display perturbed cholesterol and mitochondrial DNA organization similar to that observed for individuals with severe ATAD3A deficiency. We hypothesize that the fusion protein acts through a dominant-negative mechanism to cause this fatal mitochondrial disorder. Our data delineate a molecular diagnosis for this disorder, extend the clinical spectrum associated with structural variation at the ATAD3 locus, and identify a third mutational mechanism for ATAD3 gene cluster variants. These results further affirm structural variant mutagenesis mechanisms in sporadic disease traits, emphasize the importance of copy number analysis in molecular genomic diagnosis, and highlight some of the challenges of detecting and interpreting clinically relevant rare gene rearrangements from next-generation sequencing data

Multiple hybridization events between Drosophila simulans and Drosophila mauritiana are supported by mtDNA introgression

The study of speciation has advanced considerably in the last decades because of the increased application of molecular tools. In particular, the quantification of gene flow between recently diverged species could be addressed. Drosophila simulans and Drosophila mauritiana diverged, probably allopatrically, from a common ancestor approximately 250 000 years ago. However, these species share one mitochondrial DNA (mtDNA) haplotype indicative of a recent episode of introgression. To study the extent of gene flow between these species, we took advantage of a large sample of D. mauritiana and employed a range of different markers, i.e. nuclear and mitochondrial sequences, and microsatellites. This allowed us to detect two new mtDNA haplotypes (MAU3 and MAU4). These haplotypes diverged quite recently from haplotypes of the siII group present in cosmopolitan populations of D. simulans. The mean divergence time of the most diverged haplotype (MAU4) is approximately 127 000 years, which is more than 100 000 years before the assumed speciation time. Interestingly, we also found some evidence for gene flow at the nuclear level because an excess of putatively neutral loci shows significantly reduced differentiation between D. simulans and D. mauritiana. Our results suggest that these species are exchanging genes more frequently than previously thought

Genetic risk of neurodegenerative diseases is associated with mild cognitive impairment and conversion to dementia

Introduction Neurodegenerative diseases are a major cause of cognitive impairment and can ultimately lead to dementia. Genome-wide association studies have uncovered many genetic variants conferring risk of neurodegenerative diseases, but their role in cognitive impairment remains unexplored. Methods In the prospective, population-based Rotterdam Study, 3605 nondemented persons aged ≥55 years were genotyped, screened for mild cognitive impairment (MCI) in 2002 to 2005 and underwent continuous follow-up for dementia until 2012. Weighted polygenic risk scores of genetic variants for Alzheimer's disease (AD), Parkinson's disease (PD), and the frontotemporal lobar degeneration/amyotrophic lateral sclerosis disease spectrum (FTLD/ALS) were constructed and investigated for association with MCI and the subsequent conversion to dementia. Results In total, 360 (10.0%) persons had MCI, of whom 147 (4.1%) were amnestic and 213 (5.9%) nonamnestic. The AD risk score was associated with both MCI subtypes (odds ratio for all MCI 1.15 [95% CI, 1.03-1.28]), whereas PD and FTLD/ALS risk scores were associated only with nonamnestic MCI (odds ratios 1.15 [1.00-1.32] and 1.19 [1.03-1.37], respectively). The AD risk score, but not PD and FTLD/ALS risk scores, was associated with an increased risk of dementia (hazard ratio 1.55 [1.37-1.77]). Discussion Genetic evidence supports the view that multiple neurodegenerative pathways lead to MCI and that the subsequent conversion to dementia, primarily of the AD subtype, is mainly due to the AD pathway(s)

Artificial graphene as a tunable Dirac material

Artificial honeycomb lattices offer a tunable platform to study massless Dirac quasiparticles and their topological and correlated phases. Here we review recent progress in the design and fabrication of such synthetic structures focusing on nanopatterning of two-dimensional electron gases in semiconductors, molecule-by-molecule assembly by scanning probe methods, and optical trapping of ultracold atoms in crystals of light. We also discuss photonic crystals with Dirac cone dispersion and topologically protected edge states. We emphasize how the interplay between single-particle band structure engineering and cooperative effects leads to spectacular manifestations in tunneling and optical spectroscopies.Comment: Review article, 14 pages, 5 figures, 112 Reference

Time trend and age-period-cohort effect on kidney cancer mortality in Europe, 1981–2000

BACKGROUND: The incorporation of diagnostic and therapeutic improvements, as well as the different smoking patterns, may have had an influence on the observed variability in renal cancer mortality across Europe. This study examined time trends in kidney cancer mortality in fourteen European countries during the last two decades of the 20th century. METHODS: Kidney cancer deaths and population estimates for each country during the period 1981–2000 were drawn from the World Health Organization Mortality Database. Age- and period-adjusted mortality rates, as well as annual percentage changes in age-adjusted mortality rates, were calculated for each country and geographical region. Log-linear Poisson models were also fitted to study the effect of age, death period, and birth cohort on kidney cancer mortality rates within each country. RESULTS: For men, the overall standardized kidney cancer mortality rates in the eastern, western, and northern European countries were 20, 25, and 53% higher than those for the southern European countries, respectively. However, age-adjusted mortality rates showed a significant annual decrease of -0.7% in the north of Europe, a moderate rise of 0.7% in the west, and substantial increases of 1.4% in the south and 2.0% in the east. This trend was similar among women, but with lower mortality rates. Age-period-cohort models showed three different birth-cohort patterns for both men and women: a decrease in mortality trend for those generations born after 1920 in the Nordic countries, a similar but lagged decline for cohorts born after 1930 in western and southern European countries, and a continuous increase throughout all birth cohorts in eastern Europe. Similar but more heterogeneous regional patterns were observed for period effects. CONCLUSION: Kidney cancer mortality trends in Europe showed a clear north-south pattern, with high rates on a downward trend in the north, intermediate rates on a more marked rising trend in the east than in the west, and low rates on an upward trend in the south. The downward pattern observed for cohorts born after 1920–1930 in northern, western, and southern regions suggests more favourable trends in coming years, in contrast to the eastern countries where birth-cohort pattern remains upward

Theoretical study of Oldroyd-b visco-elastic fluid flow through curved pipes with slip effects in polymer flow processing

The characteristics of the flow field of both viscous and viscoelastic fluids passing through a curved pipe with a Navier slip boundary condition have been investigated analytically in the present study. The Oldroyd-B constitutive equation is employed to simulate realistic transport of dilute polymeric solutions in curved channels. In order to linearize the momentum and constitutive equations, a perturbation method is used in which the ratio of radius of cross section to the radius of channel curvature is employed as the perturbation parameter. The intensity of secondary and main flows is mainly affected by the hoop stress and it is demonstrated in the present study that both the Weissenberg number (the ratio of elastic force to viscous force) and slip coefficient play major roles in determining the strengths of both flows. It is also shown that as a result of an increment in slip coefficient, the position of maximum velocity markedly migrates away from the pipe center towards the outer side of curvature. Furthermore, results corresponding to Navier slip scenarios exhibit non-uniform distributions in both the main and lateral components of velocity near the wall which can notably vary from the inner side of curvature to the outer side. The present solution is also important in polymeric flow processing systems because of experimental evidence indicating that the no-slip condition can fail for these flows, which is of relevance to chemical engineers

What are the beliefs of pediatricians and dietitians regarding complementary food introduction to prevent allergy?

<p>Abstract</p> <p>Background</p> <p>The timing of complementary food introduction is controversial. Providing information on the timing of dietary introduction is crucial to the primary prevention of food allergy. The American Academy of Pediatrics offers dietary recommendations that were updated in 2008.</p> <p>Objective</p> <p>Identify the recommendations that general pediatricians and registered dietitians provide to parents and delineate any differences in counselling.</p> <p>Methods</p> <p>A 9-item survey was distributed to pediatricians and dietitians online and by mail. Information on practitioner type, gender, length of practice and specific recommendations regarding complementary food introduction and exposure was collected.</p> <p>Results</p> <p>181 surveys were returned with a 54% response rate from pediatricians. It was not possible to calculate a meaningful dietitian response rate due to overlapping email databases. 52.5% of all respondents were pediatricians and 45.9% were dietitians. The majority of pediatricians and dietitians advise mothers that peanut abstinence during pregnancy and lactation is unnecessary. Dietitians were more likely to counsel mothers to breastfeed their infants to prevent development of atopic dermatitis than pediatricians. Hydrolyzed formulas for infants at risk of developing allergy were the top choice of formula amongst both practitioners. For food allergy prevention, pediatricians were more likely to recommend delayed introduction of peanut and egg, while most dietitians recommended no delay in allergenic food introduction.</p> <p>Conclusions</p> <p>In the prophylaxis of food allergy, pediatricians are less aware than dietitians of the current recommendation that there is no benefit in delaying allergenic food introduction beyond 4 to 6 months. More dietitians than pediatricians believe that breastfeeding decreases the risk of atopic dermatitis. Practitioners may benefit from increased awareness of current guidelines.</p