An earlier study suggested that longer intervals between diagnosis and treatment of uveal melanoma are associated with worse prognosis. We evaluated whether a similar association could be observed in an independent cohort. Retrospective cohort of 336 patients with posterior uveal melanoma treated at a single referral center (2000–2011), assembled by investigators independent of the original report. We compared disease-specific (DSS) and overall survival (OS) across prespecified diagnosis-to-treatment intervals (≤ 15, 30, 45 days) using cumulative-incidence (Gray’s) and Kaplan–Meier analyses (unmatched and propensity-matched). Fine–Gray regression with treatment day as time zero estimated the subdistribution hazard ratio per 10-day delay. Tumor size and stage at diagnosis did not differ between patients treated within 30 days (prompt) and those treated after 30 days (delayed). In competing-risk analysis, delayed treatment was associated with a higher cumulative incidence of metastatic death. Kaplan–Meier OS—but not DSS—differed significantly between prompt and delayed treatment. A model of exponential tumor growth indicated that deferring treatment of a lesion of a medium-sized tumor by one month is associated with an estimated absolute increase in the 10-year competing-risk incidence of metastatic death by ≈ 0.8
BACKGROUND:Transpupillary thermotherapy (TTT) is used for selected small choroidal melanocytic tumours, either as primary treatment or as an adjunct to plaque brachytherapy. We compared long-term local recurrence and mortality outcomes after primary TTT alone, plaque brachytherapy combined with TTT (brachy+TTT), and plaque brachytherapy alone (brachy alone). METHODS:This retrospective cohort study included 850 patients with choroidal melanocytic tumours treated with eye-preserving modalities at St. Erik Eye Hospital, Stockholm, Sweden, 2008-2020. Primary treatment was TTT alone (n = 48), brachy+TTT (n = 105), or brachy alone (n = 697). Outcomes included local recurrence, local recurrence with extraocular extension (EXE), and mortality. RESULTS:At 15 years, Kaplan-Meier local recurrence-free survival was 8% after TTT alone, 34% after brachy+TTT, and 86% after brachy alone (log-rank test for trend, p < 0.001). Disease-specific survival at 15 years was 46%, 85%, and 90%, respectively (p = 0.03). In multivariable Fine-Gray regression adjusting for American Joint Committee on Cancer stage, TTT alone was associated with a higher subdistribution hazard of local recurrence (sHR, 6.7; p < 0.001) and melanoma-related death (sHR, 3.9; p < 0.001). Among patients treated for local recurrence, subsequent recurrences occurred more frequently after TTT than after treatments involving brachytherapy. The risk of EXE increased with the number of TTT sessions. CONCLUSIONS:In this single-centre retrospective cohort, TTT was associated with higher rates of local recurrence and melanoma-related mortality compared with plaque brachytherapy. Future studies should assess whether similar results are observed in external long-term cohorts; such findings would inform whether the role of TTT in the management of choroidal melanocytic tumours warrants reconsideration.
General relativity with the observed baryons alone underpredicts the dynamics of galaxies and galaxy clusters at accelerations near the product of the speed of light and the Hubble constant. Here, we develop and evaluate an emergent-scalar-field framework built on one hypothesis: ordinary matter continuously emits scalar waves (not gravitational radiation) with random, uncorrelated phases. The time-averaged intensity of the summed field separates into three parts. The stationary part, one contribution per source, reproduces Newtonian attraction. Waves arriving from all matter within the causal horizon form a fluctuating background that defines an acceleration scale gw=(3/8π) cH0≈7.9 × 10-11m s-2, fixed by measured cosmology. Interference between the local field and this background, rectified by the material medium under a single stated assumption, adds an attractive acceleration proportional to √(gN gw), where gN is the Newtonian acceleration of the baryons. Three phenomenological functions of the local matter distribution (screening, saturation, and an ionized-gas enhancement) modulate this term, motivated by, but not derived from, the covariant theory. Three constants are fixed in advance; one coefficient, γp, is calibrated on the X-COP cluster sample and frozen. On 3,187 weak-field points in 175 rotation curves from the Spitzer Photometry and Accurate Rotation Curves (SPARC) database, the calibration-free prediction attains a root-mean-square error (RMSE) of 0.228 dex (95% CI = 0.204–0.253), against 0.398 for general relativity with baryons only, 0.270 for modified Newtonian dynamics (MOND) at its standard acceleration constant, and 0.213 for MOND with a re-fitted constant. On X-COP, leave-one-cluster-out validation yields 0.072 dex, and the calibrated γp = 0.69 (0.60–0.79) lies 36% below an independent ionization estimate. Applied unchanged to 22 eROSITA clusters, the framework roughly halves the central shortfall of baryons alone but retains a radially structured under-prediction (0.435 dex overall), comparable in magnitude to that of MOND. The same model underpredicts the velocity dispersions of four of five dwarf spheroidals. Solar System and wide-binary checks are conditional on the calibrated screening and stated transport convention, and a matter-like scalar background reproduces the baryon-acoustic-oscillation sound horizon to 0.04% (matched drag-epoch prescription). All numerical results were obtained with a single released analysis pipeline.
BACKGROUND:Ocular melanoma (OM) incidence varies worldwide, but the relative impact of geographic latitude versus pigmentation genetics remains debated. We investigated whether the country-level frequency of the rs12913832 derived (G) blue-eye allele (G allele frequency), or latitude better explains international differences in OM incidence. METHODS:We performed an observational ecological study of 29 countries using age-standardized OM incidence data from the International Agency for Research on Cancer (IARC), G allele frequencies from publicly available databases, and population-weighted centroids derived from nighttime lights data. We conducted correlation, linear regression, and mediation analyses to assess the associations among latitude, G allele frequency, and OM incidence. RESULTS:In univariate analyses, both latitude and the G allele frequency were positively associated with OM incidence. In multivariate regression, latitude was no longer significant, whereas the G allele frequency explained substantially more variance and uniquely accounted for 61 times more variance (partial r2) than latitude. Mediation analysis indicated that about 92% of latitude's effect on incidence was mediated through G allele frequency. CONCLUSION:At the population level, the G allele frequency is a markedly stronger predictor of OM incidence than geographic latitude. As an ecological analysis, this study identifies a population-level association rather than individual-level genetic risk and suggests that pigmentation genetics underlie much of the international variation in OM incidence.
Background: Despite the rise of endoscopic approaches, the direct brow lift remains one of the most effective procedures for correcting brow ptosis for both functional and cosmetic indications. It continues to offer superior control when correcting brow shape, height, and asymmetry. However, visible scarring remains a concern. This systematic review was conducted to synthesize recent evidence on strategies that minimize visible scarring in direct brow lift surgery. Methods: A systematic literature search was performed to retrieve English-language publications from the past decade, discussing scar-minimization strategies in direct brow lift. A total of 124 records were identified through database searches in Ovid MEDLINE and Embase. Records were screened manually according to predetermined criteria, and those not in English, not addressing scarring, or not focused on direct brow lift were excluded. After this process, ten publications were included in the final qualitative synthesis. Results: The qualitative synthesis of all included publications (together comprising data on approximately 900 patients) revealed several strategies for scar minimization. (1) Incision beveling: A shallow cranially directed bevel between 20° and 45° preserves brow hair follicles and allows hair regrowth through the scar, providing natural camouflage. (2) Undermining: Gentle subcutaneous undermining in a limited 1-2 cm field, while preserving subcutaneous fat, allows tension-free advancement and maintains brow volume. (3) Periosteal suspension: Anchoring the mobilized brow flap to the frontal periosteum redistributes tension away from the dermal closure, maintaining elevation and improving scar quality. (4) Layered closure: Two- or three-layered wound closure with deep dermal anchoring and fine everting skin sutures minimizes dermal traction and scar widening. (5) Adjunctive measures: Evidence for topical silicone gel was inconclusive, whereas postoperative laser therapy and perioperative neuromodulator use demonstrated improved scar appearance. Across studies, outcomes were consistent, with high patient satisfaction, inconspicuous scars in over 85% of cases, and low complication or revision rates. Conclusions: Direct brow lift has historically been criticized for conspicuous scarring, contributing to the popularity of endoscopic techniques. Nevertheless, the traditional direct brow lift remains a fundamental skill in the oculofacial plastic surgeon's armamentarium, offering unmatched accuracy in brow repositioning, reliability, and symmetry. Contemporary evidence demonstrates refinements that can markedly minimize scar visibility. This systematic review and qualitative synthesis allow us to continue to refine and improve our techniques to minimize scarring in direct brow lift to the benefit of our patients.
