Methodological Appraisal of Phase 3 Clinical Trials in Geographic Atrophy.

Geographic atrophy (GA) secondary to age-related macular degeneration is a common cause of blindness worldwide. Given the recent approval of the first therapy for GA, pegcetacoplan, we critically appraise methodological aspects of the phase 3 clinical trials published so far in this disease in relation to their design, analysis and interpretation. We reviewed some of the key attributes of all phase 3 clinical trials in GA available in the main public registry of clinical trials as of 20 May 2023. The topics discussed included types of endpoints, eligibility criteria, p-value and effect size, study power and sample size, the intention to treat principle, missing data, consistency of results, efficacy-safety balance and application of results. Five phase 3 clinical trials have reported results, either partially or completely: GATHER1, DERBY/OAKS, CHROMA/SPECTRI, SEATTLE and GATE. Although there are many similarities between these trials in terms of endpoints or broad eligibility criteria, they differ in several aspects (metric of the primary endpoint, sample size, type of adverse events, etc.) that can influence the results, which are discussed. Readers should understand key methodological aspects of clinical trials to improve their interpretation. On the other hand, authors should adhere to clinical trial reporting guidelines to communicate what was done and how it was done.

Reduced choice-confidence in negative numerals.

Negative numbers are central in math. However, they are abstract, hard to learn, and manipulated slower than positive numbers regardless of math ability. It suggests that confidence, namely the post-decision estimate of being correct, should be lower than positives. We asked participants to pick the larger single-digit numeral in a pair and collected their implicit confidence with button pressure (button pressure was validated with three empirical signatures of confidence). We also modeled their choices with a drift-diffusion decision model to compute the post-decision estimate of being correct. We found that participants had relatively low confidence with negative numerals. Given that participants compared with high accuracy the basic base-10 symbols (0-9), reduced confidence may be a general feature of manipulating abstract negative numerals as they produce more uncertainty than positive numerals per unit of time.

Visual disturbances produced after the implantation of 3 EDOF intraocular lenses vs 1 monofocal intraocular lens.

PURPOSE: To compare the visual disturbances experienced by patients receiving 1 of 3 extended depth-of-focus (EDOF) intraocular lenses (IOLs) or a monofocal IOL as the control. SETTING: OMIQ-Recerca Center. Spain. DESIGN: Prospective comparative randomized double-blind study. METHODS: 22 patients were included per group. The IOLs evaluated were the AcrySof IQ Vivity (Vivity group), AT LARA 829MO (AT Lara group), or TECNIS Symfony ZXR00 (Symfony group) and the monofocal AcrySof IQ SN60WF (Monofocal group). The variables analyzed were the light distortion index (LDI), best-fit circle radius (BFC Rad ), and self-reported vision quality with a questionnaire (QoV). Outcomes were evaluated at the 3-month follow-up visit. RESULTS: Under monocular conditions, no differences between groups were detected for the LDI and BFC Rad . Under binocular conditions, significant differences in both variables were produced. The Monofocal group reported better values than Symfony ( P = .025; P = .024) and AT Lara ( P = .002; P = .002) groups. The Vivity group reported better values than Symfony ( P = .015; P = .014) and AT Lara ( P = .001; P = .001) groups. Halos were not reported by 81.8% (18) of patients in the Vivity group, 90.9% (20) of patients in the Monofocal group, 50% (11) of patients in the AT Lara group, and 59% (13) of patients in the Symfony group. CONCLUSIONS: The diffractive EDOF IOL models examined in this study induced similar visual disturbances, which were worse than those produced by the nondiffractive extended-range IOL and the monofocal IOL. The nondiffractive lens and the monofocal lens did not show differences.

First Report of Fusarium annulatum Associated with Young Vine Decline in California.

From 2018 to 2021 a decline was detected in young vineyards of both wine and table grape (Vitis vinifera L.) in seven counties across California (Kern, Monterey, Napa, Sonoma, Tulare, Yolo, and Yuba). Affected vines showed poor or no growth throughout the season, dieback, sap exudation and internal cankers around the graft union. Lack of feeder roots was detected, indicating weak root development. In some cases, graft failure was associated with the symptomatology in recently established vineyards (<3 years old). A prevalence from 5 to 50% was estimated in 10 vineyards. Affected vines (n=34) were collected by farm advisors and submitted to the laboratory. Symptomatic vines were surface disinfected with 70% ethanol for 1 minute and air dried under sterile conditions. Vascular discoloration around the graft union was observed and inspected by removing the bark using a sterile knife. Isolations were performed from the margin of lesions by placing five wood sections (1×1 mm) per vine onto potato dextrose agar acidified with 0.5 mL/L of 85% lactic acid (APDA) and incubated for 7 days at 25°C in the dark. Even though other fungi associated with young vine decline were isolated and identified as Phaeoacremonium, Ilyonectria, and Botryosphaeriaceae species, Fusarium colonies (Leslie and Summerell, 2006) were the most prevalent among all the symptomatic vines. Pure cultures were obtained by transferring single hyphal tips onto fresh PDA. After 5 days of incubation, colonies formed white aerial mycelium with orange to purple colors on the bottom. Colonies in Spezieller Nährstoffarmer agar (SNA) produced abundant microconidia that were hyaline and ovoid to elliptical, ranging from 5.4 to 10.6 (7.4) × 1.4 to 3.3 (2.4) µm in size (n=50). Straight and slightly curved macroconidia varied from 15.5 to 42.3 (23.7) × 2.6 to 5.0 (3.6) µm in size (n=50). Upon DNA extraction, the translation elongation factor 1α (tef1) and the RNA polymerase II second largest subunit (rpb2) partial gene regions were amplified and sequenced using the EF1/EF2, 5F2/7cR and 7cF/11aR pair primers, respectively (O'Donnell et al. 1998, O'Donnell et al. 2007, Liu et al. 1999). Consensus sequences were compared to the NCBI database using BLAST, showing over 99% similarity with the ex-type sequence of F. annulatum CBS 258.54 (MT010994 and MT010983). A maximum likelihood multi-locus phylogenetic analysis confirmed that all the Californian isolates cluster with F. annulatum strains. Sequences were deposited in GenBank (nos. OK888534 to OK888537). Two representative isolates (UCD9188 and UCD9416) were used for pathogenicity tests. One-year-old 'Chardonnay' vines were inoculated between the second and third node by removing a 5-mm diameter disk of the bark using a sterile cork borer and placing a 5-mm agar plug with actively growing mycelium. Five replicates per isolate including controls with sterile agar plugs were incubated under greenhouse conditions for 2 months. The experiment was performed twice. Symptoms expressed as vascular linear necrotic lesions that ranged from 25.6 to 62.8 mm and the same pathogen was recovered, thus fulfilling Koch's postulates. Fusarium annulatum Bugnic. is a morphologically and genetically diverse species that has been widely known as F. proliferatum and known to be pathogenic in more than 200 plant hosts (Yilmaz et al. 2021). Fusarium spp. have been previously reported to cause young vine decline in Australia and British Columbia, Canada (Highet and Nair, 1995; Úrbez-Torres et al. 2017). To the best of our knowledge, this is the first report of F. annulatum associated with young vine decline complex in California.

Population Structure of a Worldwide Phytophthora palmivora Collection Suggests Lack of Host Specificity and Reduced Genetic Diversity in South America and the Caribbean.

Phytophthora palmivora (Butler) is a highly destructive plant pathogen that infects tropical hosts worldwide, many of which are economically important crops. Despite the broad host range and wide distribution, the pathogen has displayed a considerable amount of variation in morphological characters, including virulence. However, the genetic variability at a global level, which is critical to understand the center of origin and the potential pathway(s) of introduction, was unclear. Here, we mapped the genetic variation of P. palmivora using isolates representing four regions, 15 countries, and 14 host species. We designed a large set of simple sequence repeat markers from the P. palmivora genome and picked 17 selectively neutral markers to screen 98 P. palmivora isolates. We found that P. palmivora populations from our collection generally did not cluster according to host; rather, some isolates from North America were generally distinct from all other populations. Isolates from South America and the Caribbean clustered and appeared to share ancestry with isolates from Asia. Populations from North America and Asia were the most genetically diverse, while the South American and Caribbean populations exhibited similar reduced genetic diversity. The isolates collected in various plantations in Colombia did not show host or geographic specificity. Our study brought a further understanding of this important plant pathogen, although the determination for hypothesized source of origin, spread, and evolution would need further sampling. The genomic resources developed in this study would facilitate further studies on P. palmivora diagnostics and management.

The numerator bias exists in millions of real-world comparisons.

Fractions are crucial, from math and science education to daily activities, but they are hard. A puzzling aspect of fractions is that people over-rely on the numerator when comparing a pair of fractions. Previous work has considered this numerator bias mostly as a reasoning mishap. Still, in a vast amount of pairwise comparisons, across many real-world domains, not just education textbooks, we report a high prior probability that the larger fraction has the larger numerator, and, for a relevant case, we provide formal arguments why. The existence of such a regularity suggests that the numerator bias may reflect a rational adaptation that detects and exploits likely events. In a pair of visual-proportion tasks (discrete and continuous fractions), we confirm that the numerator bias in participants adapts to experimented regularities. Even though weak education and math abilities play a role, adaptation to informative priors outside the classroom poses a challenge to educators, learners, and decision-makers.

Posterior Hyaloid Dissection: Let's Make It Easy with Blue.

PURPOSE: Our aim is to present in this online supplementa ry video (see www.karger.com/doi/10.1159/000486348) an easy new surgical technique using blue dye to dissect the posterior hyaloid when performing pars plana vitrectomy. PROCEDURES: Dual-Blue stain is injected in vitreous cavity just after central vitrectomy is performed. The distribution of the blue stain will allow us to know if there is a posterior vitreous detachment or not ("blue lake fashion" or "blue jelly fashion," respectively) and as an excellent visualization of the vitreous fibers is accomplished, dissection of the posterior hyaloid can be performed without difficulty. RESULTS: This procedure allows a much more simple, fast, and safe dissection of posterior hyaloid even for an inexperienced vitreoretinal surgeon. The cleavage plane between the retina and the posterior hyaloid is easily differentiated. CONCLUSIONS: A more controlled and easy dissection of posterior hyaloid during vitrectomy is accomplished with this simple technique without adding any extra cost. Message of the paper: An easy technique that allows a much easier dissection of the posterior hyaloid during vitrectomy improving visualization and decreasing risks. No extra cost, nor time is needed.

Síndrome de brugada en un paciente con síncope: presentación de un caso y revisión de la literatura / Brugada syndrome in a patient with syncope: a case report and literature review

El síndrome de Brugada es una enfermedad autosómica dominante esporádica que afecta los canales de sodio de los miocardiocitos. Clínicamente se caracteriza por síncopes recurrentes y/o muerte súbita, que en el electrocardiograma simula un bloqueo de rama derecha, acompañado de elevación peculiar del segmento ST en las derivaciones precordiales derechas (V1, V2 y V3) sin alteración cardiaca estructural. Afecta principalmente a hombres en la cuarta década de la vida y tiene mayor prevalencia en el suroeste asiático. El caso que se describe corresponde a un paciente con antecedentes personales de síncopes, a quien se le encuentra un patrón electrocardiográfico tipo-2 de Brugada y quien además tiene un hermano con historia de síncopes. Con una prueba de mesa basculantes positivo para síncope mediado neuralmente se deja este diagnóstico, pero no se descarta la sospecha inicial de síndrome de Brugada.

Brugada syndrome is a sporadic autosomal dominant genetic disease that affects cardiac sodium channels. It is clinically characterized by recurrent syncope and/or sudden death with electrocardiographic manifestations that simulate a right bundle branch block accompanied by ST-segment elevation in the right precordial leads (V1, V2 and V3) without structural cardiac changes. It mainly affects men in their fourth decade and is most prevalent in southwestern Asia. We present the case of a patient with history of syncope, type-2 Brugada electrocardiographic pattern and who has a brother also with history of syncope. The patient had a positive tilt test for neurocardiogenic syncope. He was diagnosed as neurocardiogenic syndrome, without discarding the initial suspicion of Brugada syndrome.