Circular Networks from Distorted Metrics

Trees have long been used as a graphical representation of species relationships. However complex evolutionary events, such as genetic reassortments or hybrid speciations which occur commonly in viruses, bacteria and plants, do not fit into this elementary framework. Alternatively, various network representations have been developed. Circular networks are a natural generalization of leaf-labeled trees interpreted as split systems, that is, collections of bipartitions over leaf labels corresponding to current species. Although such networks do not explicitly model specific evolutionary events of interest, their straightforward visualization and fast reconstruction have made them a popular exploratory tool to detect network-like evolution in genetic datasets. Standard reconstruction methods for circular networks, such as Neighbor-Net, rely on an associated metric on the species set. Such a metric is first estimated from DNA sequences, which leads to a key difficulty: distantly related sequences produce statistically unreliable estimates. This is problematic for Neighbor-Net as it is based on the popular tree reconstruction method Neighbor-Joining, whose sensitivity to distance estimation errors is well established theoretically. In the tree case, more robust reconstruction methods have been developed using the notion of a distorted metric, which captures the dependence of the error in the distance through a radius of accuracy. Here we design the first circular network reconstruction method based on distorted metrics. Our method is computationally efficient. Moreover, the analysis of its radius of accuracy highlights the important role played by the maximum incompatibility, a measure of the extent to which the network differs from a tree.Comment: Submitte

The staining pattern of brilliant blue G during macular hole surgery: a clinicopathologic study

Purpose.: To describe the intraoperative staining pattern of the internal limiting membrane (ILM)-specific dye Brilliant Blue G (BBG) in a cohort of patients with idiopathic macular holes; to analyze the associations of the staining pattern with pre- and postoperative variables and to correlate the staining pattern with transmission electron microscopy (TEM) of the excised ILM. Methods.: Fifty-five consecutive patients were studied. The staining pattern was divided into three subtypes based on the intraoperative appearance. The presence of a narrow rim of nonstaining around the macular hole (MH) edge was noted and measured. In the final 21 patients, the excised ILM was examined with TEM. Results.: The pattern of staining observed was categorized as uniform in 33 patients (60%), patchy nonstaining in 17 (31%), and no visible staining in 5 (9%). The staining pattern correlated with the MH stage. In the patients with uniform or patchy staining, a nonstaining rim was observed in 26 (52%) of the 50. The presence of a rim was associated with a greater hole diameter and lower postoperative visual acuity. The stain pattern correlated significantly with the amount of cellular tissue on the vitreous side of the ILM on TEM, with a greater proportion of multicellular layer membranes and new collagen in the incomplete staining groups. Conclusions.: A variety of nonstaining patterns around macular holes can be observed using BBG, and these patterns correlate to the amount of cellular tissue on the vitreous side of the ILM seen histologically. These patterns could be used to guide the ILM peeling requirement or extent in future studies

A minimum specification dataset for liquid ocular endotamponades: recommendations by a European expert panel

\ua9 2023, The Author(s). Purpose: To propose a minimum specification dataset to characterize liquid ocular endotamponades (OEs), namely silicone oil (SO), heavy SO (HSO), perfluorodecalin (PFD), and perfluoro-octane (PFO), in terms of physicochemical properties, purity and available evidence of safety, in line with ISO16672:2020. Methods: An evidence-based consensus using the expert panel technique was conducted. Two facilitators led a committee of 11 European experts. Facilitators prepared a dataset for each compound including the list of specifications relevant for the safety, identified by the group members on the basis of expertise and a comprehensive literature review. Each item was ranked by each member using a 9-point scale from 1 “absolutely to not include” to 9 “absolutely to include” in two rounds followed by discussion. Only items reaching consensus (score ≥ 7 from ≥ 75% of members) were included in the final datasets. Results: For all OEs, consensus was reached to include manufacturer, density, refractive index, chemical composition, dynamic viscosity, interfacial and surface tension, endotoxins, in vitro cytotoxicity assessment, and any evidence from ex vivo and/or in vivo tests for safety assessment. Additional specifications were added for SO (molecular weight distribution, content of oligosiloxanes with MW ≤ 1000 g/mol, spectral transmittance) and PFD/PFO (% of pure PFD/PFO in the final product, vapor pressure, chemical analyses performed for safety assessment). Conclusion: The proposed evidence-based minimum specification datasets for SO, HSO, PFD, and PFO have the potential to provide surgeons and health service purchasers with an easily available overview of the most relevant information for the safety assessment of OEs. [Figure not available: see fulltext.

Surgical interventions for degenerative lamellar macular holes

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effect of surgical interventions on postoperative visual and anatomical outcomes in people with a confirmed degenerative lamellar macular hole

Twenty-seven-gauge vitrectomy: a consecutive, single-centre case series with exclusive use over a 4-year period

\ua9 2023, The Author(s).Background: To assess the safety and effectiveness of the exclusive use of 27-gauge instruments for all vitreoretinal diseases requiring vitrectomy. Methods: In this retrospective study, 1020 consecutive surgeries were performed on 958 eyes of 848 patients using 27-gauge instruments from March 2017 to June 2021. Patients with a minimum follow-up of 3 months were included. Surgical case-mix, best-corrected visual acuity (BCVA), intraocular pressure (IOP), intra- and post-operative complications, and surgery times were recorded. Results: The study patients were followed up for averagely 11 months. Of the 1020 vitrectomies, 958 were primary procedures. Of the 148 retinal detachment (RD) cases, 138 (93%) required a single vitrectomy. Primary macular hole closure was achieved in 143 of 145 (99%) cases. The average surgical times were 55 and 38 min for RD surgeries and for all other indications, respectively. BCVA improved significantly at the final visit (20/49) compared with the pre-operative visit (20/78) (p < 0.01). IOP was similar at the pre-operative (14.8mmHg) and final (14.3mmHg) visits. Complications recorded include transient hypotony in 39 eyes, iatrogenic retinal breaks in 2 eyes, and a vitreous bleed in 1 other eye. Conclusion: This study revealed that 27-gauge vitrectomy instruments can be used for a wide range of indications, with exclusive use in certain settings. The outcomes were similar to other gauges, including for rhegmatogenous retinal detachment, with minimal complications

Folding and unfolding phylogenetic trees and networks

Phylogenetic networks are rooted, labelled directed acyclic graphs which are commonly used to represent reticulate evolution. There is a close relationship between phylogenetic networks and multi-labelled trees (MUL-trees). Indeed, any phylogenetic network $N$ can be "unfolded" to obtain a MUL-tree $U(N)$ and, conversely, a MUL-tree $T$ can in certain circumstances be "folded" to obtain a phylogenetic network $F(T)$ that exhibits $T$. In this paper, we study properties of the operations $U$ and $F$ in more detail. In particular, we introduce the class of stable networks, phylogenetic networks $N$ for which $F(U(N))$ is isomorphic to $N$, characterise such networks, and show that they are related to the well-known class of tree-sibling networks.We also explore how the concept of displaying a tree in a network $N$ can be related to displaying the tree in the MUL-tree $U(N)$. To do this, we develop a phylogenetic analogue of graph fibrations. This allows us to view $U(N)$ as the analogue of the universal cover of a digraph, and to establish a close connection between displaying trees in $U(N)$ and reconcilingphylogenetic trees with networks

Clades and clans: a comparison study of two evolutionary models

The Yule-Harding-Kingman (YHK) model and the proportional to distinguishable arrangements (PDA) model are two binary tree generating models that are widely used in evolutionary biology. Understanding the distributions of clade sizes under these two models provides valuable insights into macro-evolutionary processes, and is important in hypothesis testing and Bayesian analyses in phylogenetics. Here we show that these distributions are log-convex, which implies that very large clades or very small clades are more likely to occur under these two models. Moreover, we prove that there exists a critical value $\kappa(n)$ for each $n\geqslant 4$ such that for a given clade with size $k$, the probability that this clade is contained in a random tree with $n$ leaves generated under the YHK model is higher than that under the PDA model if $1<k<\kappa(n)$, and lower if $\kappa(n)<k<n$. Finally, we extend our results to binary unrooted trees, and obtain similar results for the distributions of clan sizes.Comment: 21page

Anti–Vascular Endothelial Growth Factor Drugs Compared With Panretinal Photocoagulation for the Treatment of Proliferative Diabetic Retinopathy: A Cost-Effectiveness Analysis

\ua9 2024Objectives: This study aimed to evaluate the cost-effectiveness of anti–vascular endothelial growth factor drugs (anti-VEGFs) compared with panretinal photocoagulation (PRP) for treating proliferative diabetic retinopathy (PDR) in the United Kingdom. Methods: A discrete event simulation model was developed, informed by individual participant data meta-analysis. The model captures treatment effects on best corrected visual acuity in both eyes, and the occurrence of diabetic macular edema and vitreous hemorrhage. The model also estimates the value of undertaking further research to resolve decision uncertainty. Results: Anti-VEGFs are unlikely to generate clinically meaningful benefits over PRP. The model predicted anti-VEGFs be more costly and similarly effective as PRP, generating 0.029 fewer quality-adjusted life-years at an additional cost of \ua33688, with a net health benefit of −0.214 at a \ua320 000 willingness-to-pay threshold. Scenario analysis results suggest that only under very select conditions may anti-VEGFs offer potential for cost-effective treatment of PDR. The consequences of loss to follow-up were an important driver of model outcomes. Conclusions: Anti-VEGFs are unlikely to be a cost-effective treatment for early PDR compared with PRP. Anti-VEGFs are generally associated with higher costs and similar health outcomes across various scenarios. Although anti-VEGFs were associated with lower diabetic macular edema rates, the number of cases avoided is insufficient to offset the additional treatment costs. Key uncertainties relate to the long-term comparative effectiveness of anti-VEGFs, particularly considering the real-world rates and consequences of treatment nonadherence. Further research on long-term visual acuity and rates of vision-threatening complications may be beneficial in resolving uncertainties